Chapter 5 Synthesis of 5-substituted

dipyrromethanes and their uses in the synthesis of expanded porphyrins and core-modified expanded porphyrins

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252

CHAPTER 5 SYNTHESIS OF 5-SUBSTITUTED DIPYRROMETHANES AND

THEIR USES IN THE SYNTHESIS OF EXPANDED PORPHYRINS AND CORE-MODIFIED EXPANDED PORPHYRINS

5.1 Introduction The expanded porphyrins1,2 are synthetic analogues of porphyrin and differ from porphyrins more than 18 π electron in conjugated pathway either due to an increased number of pyrroles or due to multiple of meso-carbon bridges. The expanded porphyrins bind to various anions3 and they are used in materials and medicinal chemistry. The expanded porphyrins coordinate with large cations like lanthanide and actinides, anions complexation and transport, maganetic resonance imaging constrast agents, photodynamic therapy sensitizer and building blocks in nonlinear materials. The expanded porphyrins containing five pyrroles or heterocycles are immediate higher homologues of porphyrins. There are three types of expanded porphyrin system containing five pyrrole or heterocyclic rings pentaphyrin, sapphyrin and smaragdyrin4 (Chart 5.1). Selected covalent5,6 and non-covalent7,8 interactions have been undertaken. The synthesis of sapphyrin and related expanded porphyrins by condensation of dipyrromethanes and tripyrromethane in presence of acid and their non-covalent interactions has been reported in the present chapter.

NHN

N

NHNH

N

NH N

HN

NNH

N

HN

HN

NN

HNN

NH

+ 1 pyrrole+1 meso carbon

- 1 meso carbon

-1 meso carbon

+1 meso carbon-1pyrrole

pentaphyrin

smaragdyrin sapphyrin

porphyrin

Chart 5.1

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The sapphyrins with N2S3 core were prepared by [3+2] condensation of bithiophene diol and 16-thiatripyrrane under standard acid catalyzed conditions9.The desired mono-functionalized porphyrin building blocks were synthesized by following the literature methods10. The porphyrin-sapphyrin dyads was synthesized by coupling of 1 equiv of sapphyrin building block with 1 equiv of porphyrin building blocks in the presence of Pd2(dba)3/AsPh3 in toluene/triethylamine at 50 °C. This dyad has been used for fluorescent anion sensor. The protonated thiasapphyrin unit binds with anions.

N

S N

SH +

S

S

N

N

S

N

S N

S

S S

NN

S

I

1. Pd2(dba)3, AsPh32. Toluene, Et3N

Scheme 5.1: Synthesis of porphyrin-sapphyrin dyads

Covalently linked multiporphyrinic arrays have attracted the attention of chemists for understanding electron and energy transfer11 and as functional materials.12 Meso–meso linked porphyrin arrays13 possess a unique position in it they are directly linked, favourable for rapid energy and electron transfer, and show enhanced nonlinear optical effects.14 The linear porphyrin arrays which have large π-conjugated electrons have been shown to form molecular wires with strong electronic interactions due to an increased delocalization pathway.

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Noncovalent complexes assembled from carboxylate-bearing porphyrins and anion binding sapphyrins are described15. The sapphyrins “expanded porphyrin” macrocycles that differ from their simpler porphyrin “cousins” in several important ways. Containing five, rather than four pyrrole subunits, the sapphyrins do not coordinate cations readily. However, when mono- or diprotonated, they act as excellent receptors for a variety of anions, including fluoride and phosphate, and to a lesser extent other halides and carboxylates.16 carboxyl-substituted porphyrin could serve as both a simple-to-bind anionic substrate and a high-energy donor and the protonated sapphyrin moiety would function both as the geometry-inducing, carboxylate-binding receptor and the critical (low) energy acceptor.

5.2 Synthesis of 5-aryl and 5,5’dialkyldipyrromethane The direct synthesis of dipyrranes from aldehydes and pyrrole gives a mixture of oligopyrromethane and separation of each oligopyrromethane is difficult. In 1994 several group reported the synthesis of dipyrrones. In early 1994, the reaction of stoichiometric amount of pyrrole with aromatic aldehydes in AcOH at room temperature lead the formation of dipyrromethanes in moderate yields. 5.2.1 Homogeneous acid catalyzed synthesis of dipyrromethane Acid catalysed condensation of aldehydes and ketone with pyrrole is an important method for the synthesis of dipyrromethane17. Dipyrromethane are macrocycles that consist of two pyrrole rings linked through the pyrrole 2 and 5 positions by meso carbon atom. In most cases the meso position has either no substituted or a single aryl or dialkyl or aryl substituted.

NH

H

HR C HO

O

R2R1

NH HN

HR

NH HN

R2R1

R = HR = CH3

R1 = CH3R2 = CH3

Scheme 5.2: Acid catalysed synthesis of dipyrromethane

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255

Meso or 5-substituted dipyrromethanes are widely being used as essential building blocks for the synthesis of a variety of functional porphyrins and (contracted and expanded) porphyrin analogues18.Several methods have been reported for the synthesis of 5-substituted dipyrromethane by the condensation of an aldehyde and pyrrole using various combination of acid and solvents in most cases the large excess of pyrrole was used without any other solvent in order to achieve suppression of polymerization to form dipyrromethane in moderate yields in the presence of homogeneous acid catalyst such as triflouroacetic acid, BF3.OEt2 and propionic acid at room temperature (Scheme 5.2). 5.2.2 Cation exchange resin based catalysed synthesis of dipyrromethane The heterogeneous solid acid catalyst has been used for the synthesis of dipyrromethanes19. The macroporosity and acidity of these cation exchange resins play a crucial role in the synthesis of dipyrromethane. These resins are the functional resin with a styrene divinylbenzene copolymer matrix having sulfonic acid groups. Functional synthetic cation exchange resins serve as efficient industrial heterogeneous catalysts, potentially useful in the area of fine chemical synthesis.

Thus the condensation of pyrrole with benzaldehyde in the presence of various cation exchange resin afforded very good yield of meso-phenyl dipyrromethane (Scheme 5.3). Among the different polymeric cation exchange resins used, T-63 and indion-130 resins were found to be more suitable with respect to the product yields.

NH

CHO

R1

R2R3

+NH HN

R1

R3R2

cation exchangeresin

R1 = R2 = R3 = HR1 = H, R2 = R3 = ClR1 = F, R2 = R3 = HR1 = CH3, R2 = R3 = HR1 = NO2, R2 = R3 = HR1 = OCH3, R2 = R3 = HR1 = Cl, R2 = R3 = HR1 = H, R2 = NO2, R3 = H

Scheme 5.3: Cation exchange resin based catalysed synthesis of dipyrromethane

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256

5.2.3 Synthesis of functional dipyrromethane The functional dipyrromethane react with oxidizing reagent such as DDQ in dichloromethane gave the dipyrromethane. Further the reaction of dipyrromethane with borontrifluoro etharate in toluene gave the BODIPY20 in quantitative yield (Scheme 5.4). BODIPYs 4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacenes.

Moreover, dipyrromethanes are the precursors of BODIPY dyes (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene or boron dipyrromethene), which are currently receiving increasing attention due to their valuable properties, such as the relatively high absorption coefficients and fluorescence quantum yields, high (photo) chemical stability, and improved synthetic availability.

NH HN

NO2

Et

Et

EtOOC

Et

Et

COOEtNH N

NO2

Et

Et

EtOOC

Et

EtN N

NO2

Et

Et

EtOOC

Et

Et

COOEtBF F

DDQCH2Cl2

BF3.OEt2tolueneEt3N

COOEt Scheme 5.4: Synthesis of functional dipyrromethane

5.2.4 Molecular iodine and tin chloride catalyzed convenient synthesis of meso-

substituted dipyrromethanes The reaction at room temperature of an aromatic aldehyde with pyrrole in the presence of iodine, acetic acid catalyzed to produce meso-substituted dipyrromethane.21 The meso substituted dipyrromethane is purified by crystallization and column chromatography on silica with eluent containing methanol: benzene. The reaction is compatible with aromatic aldehydes.

The synthesis of meso substituted dipyrromethane by condensation of pyrrole with various aldehyde using SnCl2.2H2O in water as an efficient catalyst under stirring at room temperature22 (Scheme 5.5). It is reported that aromatic aldehydes with strong electron withdrawing substituent on the ring require longer reaction time giving low to

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257

moderate yields of the corresponding meso substituted dipyrromethane. The use of water as a cheap and non-toxic solvent for organic reactions is of particular interest due to the increasing environmental concerns.

NH

CHO

X

+NH HN

X

iodineacetic acid

X = HX = CH3X = OCH3X = OHX = NO2X = ClX = BrX = F

Scheme 5.5: Molecular iodine and tin chloride catalyzed convenient synthesis of meso substituted dipyrromethanes

5.2.5 Synthesis of dipyrromethanes and bis-(heterocyclyl)methanes Most of the dipyrromethanes were synthesized by the reaction of pyrrole and aldehyde or ketones in the presence of acid, but In 2005 Hundal, M. S. et. al. have introduced the novel synthetic model for the synthesis of meso-substituted and meso-unsubstituted dipyrromethane23. They have used oxazinanes and an oxazolidine in the synthesis of a number of 5-substituted dipyrromethanes24. Oxazinanes have been reacted with pyrrole and/or its combination with other carbon nucleophiles under acid (TFA) catalyzed reaction conditions25(Scheme 5.6). All these reactions can be visualized as an extension of carbon transfer reactions26.

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258

NH

O

N

OR2

H

R1 R1

R1 CH2CN

HCH3

H3C

H3C N

R3

N N

R2 H

R3R3

CH3CN/H+

N2/RT to reflux+ +

R2 = 4-OCH3C6H4, R3 =HR2 = 3,4-di(OCH3)C6H3, R3 = HR2 = 3,4,5-tri(OCH3)C6H2, R3 = HR2 = Ph, R3 = HR2 = 2-NO2C6H4, R3 = HR2 = 3-NO2C6H4, R3 = HR2 = 4-NO2C6H4, R3 = HR2 = R3 = HR2 = 4-OCH3C6H4, R3 =CH3R2 = 3,4-di(OCH3)C6H3, R3 = HR2 = 3,4,5-tri(OCH3)C6H2, R3 = HR2 = Ph, R3 = HR2 = 2-NO2C6H4, R3 = HR2 = 3-NO2C6H4, R3 = HR2 = 4-NO2C6H4, R3 = HR2 = R3 = H

R1 = H, R2 = 4-OCH3C6H4 R1 = H, R2 = 3,4-di(OCH3)C6H4 R1 = H, R2 = 3,4,5-tri(OCH3)C6H4R1 = Ph, R2 = HR1 = 2-NO2C6H4, R2 = HR1 = 3-NO2C6H4, R2= HR1 = 4-NO2C6H4, R2 = HR1 = R2= H

Scheme 5.6: Synthesis of dipyrromethanes and bis(heterocyclyl)methanes

5.2.6 Synthesis of dipyrromethane in presence of ILs To avoid using liquid acid and to minimize the amount of harmful organic solvents used in chemical process are the focuses in green chemistry. Ionic liquids have been used as catalytic species and alternative solvents to replace the traditional solvents27. The ionic liquid [Hmim]BF4 was used as catalytic species and reaction medium under mild reaction conditions (Scheme 5.7). Generally, in all instances, the condensation of ketones and pyrrole was proceeded at 0°C or room temperature to give the corresponding dipyrromethanes in moderate yields in the presence of ionic liquid [Hmim]BF4.

NH HN

R1 R2

NHO

R2R1

R1 = R2 = CH3R1 = CH3, R2 = C2H5R1 -R2 = (CH2)5R1 = CH3, R2 = C6H5

[Hmim]BF4

0 °C

Scheme 5.7: Synthesis of 5,5-disubstituted dipyrromethane

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259

5.2.7 Organocatalytic synthesis of dipyrromethanes The first organocatalytic synthesis of dipyrromethanes has been achieved by the reaction of aldehydes with N-methylpyrrole in the presence of catalytic amounts of pyrrolidinium tetrafluoroborate. This convenient method represents an improvement with respect to previous protocols because the products are obtained directly from the aldehydes under mild reaction conditions, with a relatively small excess of N-methylpyrrole, and in the presence of a catalytic amount of promoter28 (Scheme 5.8). The products are obtained in chemical yields similar to those obtained with existing methods.

N

CHO

R1

+N N

R1

NH H

BF4

CH3 CH3 H3C

R1 = C6H11R1 = 4-NO2PhR1 = PhCH2HC2R1 = 2-thienyl

Scheme 5.8: Organocatalytic synthesis of dipyrromethanes The utility of thiourea dioxide as an efficient organocatalyst for developing “greener” methodologies for other organic reactions as well. Accordingly to use TUD29 as catalyst to develop an efficient organocatalytic multicomponent synthetic approach for the library synthesis of heterocycles of potential biological applications for various purposes30. The reaction aldehyde with pyrrole in presence of catalytic amount of TUD (5 mol%) gave dipyrromethane which was purified by column chromatography by using ethyl acetate: hexane (4 : 6) as eluent.

NH

CHO

X

+NH HN

X

X = HX = CH3X = OCH3X = OHX = NO2

S

C

O O

N N HH

H H

Scheme 5.9: Hydrogen bond directed synthesis of dipyrromethane

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260

5.3 Synthesis of tripyrromethanes A broad range of tripyrranes can be synthesized by the reaction of aldehydes with pyrrole in presence of organic acids31. This reaction however is not selective, and it gives a mixture of dipyrromethanes, tripyrranes32 and tetrapyrroles. The yields of tripyrranes can be optimized via changing the ratio of aldehyde to pyrrole. Due to lack of stability and the existence of the tripyrranes as a mixture of diastereomers and regioisomers contributed to the purification problems. Consequently, tripyrromethane were often used in a partially purified state. The only exception was tripyrrane possessing trifluoromethyl groups are solid and they are purified by recrystallization33.

NH

HNNH

R R

NH

RCHO+TFA

R = 3,4,5(OCH3)3C6H4R = 4-OCH3C6H4R = 2,4,6Me3C6H2R = C6H5R = C6F5 Scheme 5.10: Synthesis of tripyrromethane

5.4 Synthesis of core modified tripyrromethanes Core modified tripyrromethanes34,35 were synthesized by the reaction of 2,5-[bis-phenyl)hydroxymethyl]thiophene36,37 which were synthesized by the reaction thiophene n-BuLi and TMEDA in hexanes under nitrogen atmosphere in refluxing temperature followed by corresponding aromatic aldehyde, and excess of pyrrole in presence of acid.

SS

2.3eq.TMEDAHaxene/ reflux

NH2.2eq. n-BuLi

OHHO

R R

aldehyde/ THFH+ NH

S

HN

RR

Scheme 5.11: Synthesis of core modified tripyrromethane

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261

5.5 Synthesis of sapphyrin and related expanded porphyrins The first sapphyrin was synthesized serendipitously during the total synthesis of vitamin B12. The macrocyclic core of sapphyrin is larger than porphyrin is less suited for metal coordination, but more suited to anion binding on protonation two conformations have been observed experimentally in sapphyrins and their hetero analogues. The relative stability of these conformations depends on peripheral substitution, core modifications and protonation state.

N NH

NNH

NH

NH N

HNNH

NH

NH N

HHNNH

NH

H H

Chart 5.2

Sapphyrin and related expanded porphyrinoids have been large surface area as compared to normal porphyrins and they are fluorescent through excitation at lower energy making them attractive as mimics of naturally occurring chlorophylls as key electron donors in photosynthesis. The non-covalent interactions of sapphyrin have been designed based on the both oligonucleotides and carboxylate anion system as models for photosynthesis. 5.5.1 Synthesis of sapphyrin by Rothemund method Synthesis of meso-substituted system usually direct condensation of pyrrole and aldehydes are called the Rothemund-Lindsey protocol or its variant. The modern approach to β-substituted system involved the condensation of appropriate pyrranes such as dipyrromethane or tripyrranes. Direct linkage between cyclic subunit (‘O’ bridges are created oxidatively at the time of macroclyclization or already present in starting materials. Bridge containing more than one carbon are used such as McMurry coupling or witting reaction. Reaction on preformed macrocycles, extraction and vacatization are also used in the synthesis of porphyrinoids.

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262

Rothemund condensation of pyrrole and benzaldehyde gave 5,10,15,20-tetraphenyl porphyrin, 21-aza-21carba-5,10,15,20-tetraphenylporphyrin and 5,10,15,20-tetraphenylsapphyrin (TPSH3) in ~ 1% yield38. The protonation of TPSH3 acts as a trigger for structural transformational involving a flip of the pyrrole units which relocate the 27-NH pyrrolic nitrogen from the periphery into the centre of the macrocycle. Sapphyrin is the simplest member in the class of expanded porphyrins. The molecule possesses an overall aromatic 22π-electron annulenes framework. The structural and spectral properties of TPSH3 are important in the selective anion binding and photodynamic therapy.

NH NHN

HN

NN

NH N

HN

1. 1 BF3 OEt2 /CH2Cl22. chloranil, reflux 1h.

+ +

CHO

N

HCNH

NHN

TPPH2 CTPPH2 TPSH3

NH+

Scheme 5.12: Synthesis of sapphyrin by Rothemund method

5.5.2 Synthesis of sapphyrin from dipyrromethane The acid catalyzed condensation of dipyrromethane in dry dichloromethane followed by chloranil oxidation gave sapphyrin as major product in addition to normal porphyrin39. The product distribution and the isolated yields were dependent on the nature of the acid catalyst and its concentration. Porphyrin was isolated in 3% yield using 0.1 equivalent of TFA while porphyrin and sapphyrin were formed in 9.5% and 3% yields respectively using 2 equivalents of TFA which is due to different extents of acidolysis under the reaction conditions. Substituted dipyrromethanes also show a similar behaviour in TFA and the yields were dependent on the steric bulk of the substituent.

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263

No sapphyrin was formed when the acid catalyst was changed to toluene p-sulfonic acid. However, using 0.1 equivalent of p-TsOH, the N-confused porphyrin40,41 and the normal porphyrin were isolated in 7% and 9.5% yields respectively. On increasing the amount of p-TsOH to 1 equivalent, the major product was N-confused porphyrin and porphyrin was the minor product. The substituted dipyrromethanes also gave N-confused porphyrins in less than 1% yield. Reaction of dipyrromethane in dry dichloromethane containing BF3 .OEt2 as the catalyst gave only porphyrin and polymeric products. When HBr was used as catalyst only porphyrin formed.

NH NHN

HN

NNH NH

HNHNNN

N

NH N

HN

1. 1 equiv. TFA /CH2Cl22. chloranil, reflux 1h.

+ +

Saphyrin X = S, Se

NH HN

Scheme 5.13a: Synthesis of sapphyrin from dipyrromethane

1.PTSA /CH2Cl22. chloranil, reflux 1h. N

NHN

HN

N

HCNH

NHN+

NH HN

Scheme 5.13b: Synthesis of N-confused porphyrin from dipyrromethane

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264

5.5.3 Synthesis of core modified sapphyrin from tripyrromethanes The core modified porphyrins have been synthesized by acid catalysed condensation of single precursor modified tripyrranes which was synthesized by acid catalysed condensation of 2,5-bis(1-hydroxymethyl phenyl)thiophene / selenophene with excess of pyrrole, followed by oxidation with chloranil in organic solvents. The product distribution in this reaction depending on the nature of the acid catalyst used only sapphyrins were isolated under Lewis acid conditions while protic acid catalysts gave rubyrins and X2TPP(dithia-,diselenaand dioxatetraphenylporphyrins) in addition to sapphyrins.

NH

X

HN

N N

XHN

XN N

H

NHN

XXN

X N

X

1. 1equiv. TFA /CH2Cl22. chloranil, reflux

+ +

Saphyrin X = S, Se 18π 22π 26π

Scheme 4.14: Synthesis of core modified expanded porphyrins 5.5.4 Synthesis of sapphyrin from diols The reaction of diol with pyrrole in dichloromethane containing 1 equivalent of TFA as the catalyst followed by chloranil oxidation gave porphyrin, sapphyrin and rubyrin in 13%, 27% and 9% yield.42,43 The product distribution and isolated yields were dependent on the nature of the protic acid, TFA gave maximum yield of the products relative to p-TsOH and HBr. The effect of acid catalyst concentration on the product distribution and the yields were also followed using diol as the substrate at three concentrations of TFA. The synthesis of 26,28-dioxa and dithia sapphyrins have been performed by a similar reaction under BF3.OEt2 catalysis 44.

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265

1. protic acid /CH2Cl22. chloranil

NHS

HO OH+

N N

XHN

XN NH

NHNXX

N

S N

S+ +

X = S, SeSapphyrin Rubyrin

Scheme 5.15: Synthesis of sapphyrin from diol

5.5.5 Synthesis of sapphyrin by [3+2]approach The sapphyrin has been synthesized by known [3+2] approach by condensation of tripyrrane with bithiophene diol in dichloromethane with one equivalent of TFA gave the desired core modified sapphyrins in moderately good yields45. Change of catalyst from protic acid to Lewis acid changes the product distribution and yield. The use of BF3OEt2 (3.05 × 10-5 M) as the catalyst and thia-tripyrromethane as the substrate under similar conditions gave two additional products core modified porphyrin and rubyrin in addition to sapphyrin in 4, 2 and 30% yield respectively. A higher concentration of BF3OEt2 (6.05 × 10-5 M) produced more of porphyrin. The cyclization has to occur through the formation of a carbocation in diol by the acid catalyst. The sole formation of the expected sapphyrins with one equivalent of TFA indicates that the generation of carbocation occurs through protonation followed by elimination of water from diol. The formation of additional products core modified porphyrin and rubyrin in the presence of BF3OEt2 catalysts can be explained by acidolysis of tripyrromethanes on the time scale of sapphyrin formation in addition to carbocation generation. It is possible that the metal on the Lewis acid coordinates to the heteroatom on the tripyrrane, triggering its acidolysis. The observed increase in the yields of porphyrin and rubyrin at the expense of sapphyrin on increasing the concentration of Lewis acid supports such a possibility.

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266

NH

X

HN

SS

N N

1. 1equiv. TFA /CH2Cl22. chloranil

36SS

HO OH+

S

Scheme 5.16: Synthesis of sapphyrin by [3+2]approach

5.5.6 Reaction of dipyrromethane with tripyrromethane The synthesis of pentaphyrins46 which is the first example of a [22] π-electron macrocycle analogous to the porphyrins (i.e. bearing five pyrrole rings and five methine bridges) have been done by the condensation of the known dipyrrylmethane with the dialdehyde in the presence of 33% hydrobromic acid in acetic acid followed by the oxidation with chloranil afforded pentaphyrin. The dialdehyde was prepared from the corresponding dibenzyl ester by hydrogenolytic cleavage of the benzyl ester groups and successive treatment of the dicarboxylic acid obtained with trifluoroacetic acid and triethyl orthoformate. This compound is aromatic in line with [22] annulenoid formation. The [24] pentaphyrin are unstable and nonaromatic. An attempt to a fully meso-substituted pentaphyrin yielded N-fused system47.

N

N

HNN

NH

NH

NH

HN

HNNH

OHCCHO

H3C

H3C CH3

CH3

H3CO2CH2CH2C

H3C

H3C CH2CH2CO2CH3

CH2CH2CO2CH3

CH3H3C

H3C

H3CCH3 H3C

CH2CH2CO2CH3

CH2CH2CO2CH3

CH3

CH2CH2CO2CH3H3C

HBr-AcOHchloranil

+

Scheme 5.17: Synthesis of expanded porphyrin

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267

5.6 Results and Discussion 5.6.1 Synthesis of diols from substituted acetophenone and benzaldehyde Mostly the dipyrromethane were synthesized by the reaction of aldehyde, ketone with large excess of pyrrole in presence of hazardous acid catalyst for example BF3 etharate, TFA, p-TsOH and methane sulfonic acids, removal of these hazardous acid is very difficult. Keeping all these views in mind here we have developed the novel methodology for the formation of dipyrromethane catalysed by novel organocatalyst as diol. In this method pyrrole was used in two equivalent and removal of organocatalyst was very easy and reusable.

Bis-diols are the important precursor for the synthesis of core modified porphyrins and porphyrinogen. Bis-diols consist of two aryl or alkyl groups directly linked through the thiophene or furan 2 or 5-position. Thiophene was added to a solution of n-BuLi and TMEDA in hexanes under nitrogen atmosphere. Thus dilithiothiophene suspension was then added dropwise to a solution of acetophenone or corresponding aromatic ketones in anhydrous THF cooled to 0°C. After completion of the reaction, reaction mixture was extracted with ethyl acetate and dried over Na2SO4, and concentrated to give yellow oil. The crude product was precipitated by the slow addition of hexanes to give 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)methyl] thiophene (Scheme 5.18), as white amorphous powder.

2a. R1 = CH3, R2 = C6H52b. R1 = CH3, R2 = C6H5OCH32c. R1 = CH3, R2 = C6H5Cl2d. R1 = CH3, R2 = C6H5NO22e. R1 = CH3, R2 = C6H5Br2f. R1 = C6H5, R2 = C6H5

SOHHO

R2

R1 R1

R2S

2.2eq. n-BuLi2.3eq.TMEDAHaxene/ reflux S

Li Li

XO

CH3

THF

X = HX = OCH3X = ClX = BrX = NO2

1 2

Scheme 5.18: Synthesis of 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)methyl]

thiophene

The structure of the compound was confirmed by different spectroscopic data. In 1H NMR spectrum of compound thiophene two sharp singlet at 1.90 and 2.51 ppm were assigned for six methyl protons and two hydroxy group protons, three doublets at 6.64, 7.24 and 7.33 ppm with coupling constant 4.4, 8.7 and 8.8 Hz were assigaryl protons and finally remaining four aryl protons respectivelycompound was charecterized by compound 2,5-bis[(1-(4two peaks at 45.25 and 74.31 ppm were assigned for methyl carbon and meso carbon, peak at 123.95 ppm was assigned for assigned for aryl carbon were assigned for α-thiophenic carbon and quartenary carbon respectively.

Figure 5.1: 13H NMR spctrum of 2,5methyl]thiophene

268

The structure of the compound was confirmed by different spectroscopic data. H NMR spectrum of compound 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)methyl]

thiophene two sharp singlet at 1.90 and 2.51 ppm were assigned for six methyl protons and two hydroxy group protons, three doublets at 6.64, 7.24 and 7.33 ppm with coupling constant 4.4, 8.7 and 8.8 Hz were assigned for two thiophenic protons, four aryl protons and finally remaining four aryl protons respectively (Figure compound was charecterized by 13C NMR spectrum, in 13C NMR spectrum of

(4-nitrophenyl-1-hydroxymethyl)methyl]thiophene (two peaks at 45.25 and 74.31 ppm were assigned for methyl carbon and meso carbon, peak at 123.95 ppm was assigned for β-thiophenic carbon, 129.55 and 130.48 ppm were assigned for aryl carbon and finally three peaks at 140.71, 140.14 and 150.49 ppm

thiophenic carbon and quartenary carbon respectively.

H NMR spctrum of 2,5-Bis[(1-(4-nitrophenyl-methyl]thiophene (2d)

Chapter 5

The structure of the compound was confirmed by different spectroscopic data. hydroxymethyl)methyl]

thiophene two sharp singlet at 1.90 and 2.51 ppm were assigned for six methyl protons and two hydroxy group protons, three doublets at 6.64, 7.24 and 7.33 ppm with

ned for two thiophenic protons, four Figure 5.1). Finally

C NMR spectrum of hydroxymethyl)methyl]thiophene (Figure 5.2)

two peaks at 45.25 and 74.31 ppm were assigned for methyl carbon and meso carbon, thiophenic carbon, 129.55 and 130.48 ppm were

and finally three peaks at 140.71, 140.14 and 150.49 ppm thiophenic carbon and quartenary carbon respectively.

-1-hydroxymethyl)

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269

SHO

H3COH

CH3

O2N NO2

Figure 5.2: 13C NMR spctrum of 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)

methyl]thiophene(2d) 5.6.2 Diol catalyzed synthesis of dipyrromethane The condensation of aldehyde or ketones with large excess of pyrrole in the presence of strong acid such as hydrochloride, triflouroacetic acid, methanesulfonic acid and borontrifluoro etharate gave dipyrromethane. However all these acids are hazardous, corrosive and their removal from the reaction mixture were very difficult.

Keeping all the view in the mind we have develop a novel synthetic method for the preparation of meso-5,5-disubstituted and 5-substituted dipyrromethane in good to excellent yield at room temperature in the presence of catalytic amount of diols (Scheme 5.19). This simple methodology provided one pot synthesis of dipyrromethane. In this regard we have synthesized a series of dioles starting from substituted acetophenone and different substituted benzaldehyde.

Chapter 5

270

NH HN

R1 R2

NH O

R2R1

SOH

R'H3C

OH

R"CH3

DCM

5a. R1 = R2 = CH35b. R1 = CH3, R2 = C2H55c. R1 = R2 = CH2CH2CH35d. R1 = CH3, R2 = CH2CH2CH2CH35e. R1 = H, R2 = C6H55f. R1 = CH3, R2 = C6H55g. R1 = H, R2 = p-OCH3C6H45h. R1 = H, R2 = 3,5-di-t-bu-p-OH-C6H45i. R1 = H, R2 = 3,5-di-OCH3-p-OH-C6H45j. R1 = H, R2 = C6F55k. R1 = H, R2 = 2,4,6-trimethyl-C6H2

R' = R'' = 4-NO2Ph

2d

3 4 5

Scheme 5.19: Synthesis of 5,5-disubstituted and 5-substituted dipyrromethane

The reaction of pyrrole with dialkyl ketones, alkyl aryl ketone and aromatic aldehydes in the presence of 2,5-bis[(1-(4-methoxy-phenyl-1-hydroxymethyl)methyl]thiophene, 2,5-bis[(1-(4-chloro-phenyl-1-hydroxymethyl)methyl]thiophene and 2,5-bis[(1-(4-nitro-phenyl-1-hydroxymethyl)methyl]thiophene gave the 5-substituted and 5,5-dimethyldipyrromethane in moderate to good yields depending on the ketones and aldehydes used in the reaction.

The reaction of acetone or benzaldehyde with pyrrole at room temperature for 24h in the presence of 2,5-bis[(1-(4-methoxy-phenyl-1-hydroxymethyl)methyl]thiophene, 2,5-bis[(1-(4-chloro-phenyl-1-hydroxymethyl)methyl]thiophene and 2,5-bis[(1-(4-nitro-phenyl-1-hydroxymethyl)methyl]thiophene gave 5,5-dimethyldipyrromethane in 45% 50% and 65% yields respectively. However 2,5-bis[(1-(4-methoxy-phenyl-1-hydroxymethyl) methyl]thiophene was found not so effective as 2,5-bis[(1-(4-chloro-phenyl-1-hydroxymethyl)methyl]thiophene and 2,5-bis[(1-(4-nitro-phenyl-1-hydroxymethyl)methyl] thiophene in which comparable yields of dipyrromethane(Table 5.1). Neverthless, condensation of benzaldehyde with pyrrole in the presence of 2,5-bis[(1-(4-nitro-phenyl-1-hydroxymethyl)methyl]thiophene afforded 5-phenyldipyrromethane in higher yields. The better yield was observed in the presence of diol starting from acetophenone having the electron withdrawing group at para-position, special in the presence of 4-nitroacetophenone. The 2,5-bis[(1-(4-nitro-phenyl-1-hydroxymethyl)methyl]thiophene showed the very good hydrogen bonding between hydroxy group of catalsyt and carbonyl

Chapter 5

271

group of ketone and aldehyde thats why the formation of dipyrromethane takes less time and give good yields. A very low yield was observed in the presence of diol starting from p-substituted benzaldehyde this might be scrambling and takes several day for the completion of the reaction.

Pyrrole and benzaldehyde were taken in CH2Cl2 (5 mL). Catalyst 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)methyl]thiophene (0.5 equivalent) was added to the reaction mixture, which was stirred at room temperature for appropriate time given in table (table 5.1). The reaction progress was monitored by thin layer chromatography (TLC). After the completion of reaction, the solvent was removed under reduced pressure and crude product, was subjected to column chromatography over silica gel (60-120 mess) eluting with petroleum ether-chloroform (8:2, v/v) to afford pure corresponding 5-phenyl-dipyrrromethane (Entry 9) in 77% yield. Further elution of the column with chloroform-methanol (9:1, v/v) gave the catalyst.

Table 5.1: Diol catalysed synthesis of dipyrromethane in dichloromethane under different reaction conditionsa

Entry Ketone Catalystb Reaction temp.

Reaction time (h).

Dipyrromethane Yield c

1 acetone 2b rt 24 5a 55 2 acetone 2c rt 24 5a 60 3 acetone 2d rt 24 5a 70 4 Ethylmethyl ketone 2d rt 24 5b 65 5 3-heptanone 2d rt 24 5c 55 6 2-heptanone 2d rt 24 5d 55 7 benzaldehyde 2b rt 8 5e 65 8 benzaldehyde 2c rt 8 5e 68 9 benzaldehyde 2d rt 8 5e 77

10 4-methoxy benzaldehyde 2d rt 8 5g 60 11 tolualdehyde 2d rt 8 5f 65 12 3,5-(C(CH3)3-4-hydroxy-

benzaldehyde 2d rt 8 5h 60

13 3,5-(OCH3)2-4-hydroxy-benzaldehyde 2d rt 8 5i 58

14 Pentafluorobenzaldehyde 2d rt 12 5i 55 15 mesitaldehyde 2d rt 12 5j 54

aReaction conditions: ketone (10 mmol), pyrrole (20 mmol), catalyst (5 mmol), DCM (5 ml), bCatalyst was prepared by usual method. cIsolated yield.

Chapter 5

272

A peak at 3345 cm-1 in IR spectrum was assigned for pyrrolic NH group in the molecule. In 1H NMR spectrum of compound 5-phenyldipyrromethane a singlet at 5.45 ppm was assigned for one meso proton, a singlet at 5.93 ppm was assigned for tow β-pyrrolic protons, three multiplets at 6.18, 6.66 and 7.22 ppm were assigned for two β-pyrrolic protons, two α-pyrrolic protons and five aryl protons. A broad singlet at 7.82 ppm was assigned for two pyrrolic NH protons (Figure 5.3). In 13C NMR spectrum of 5-phenyldipyrromethane a peak at 43.84 ppm was assigned for meso carbon, two peaks at 107.04 and 108.29 ppm were assigned for β-pyrrolic carbon and two peaks at 117.19 and 126.88 ppm were assigned for α-pyrrolic carbon another two peaks at 128.33 and 128.55 were assigned for aryl protons and finally two peaks at1 32.47 and 142.02 ppm were assigned for two aryl quaternary carbon respectively (Figure 5.4).

NH HN

Figure 5.3 : 1H NMR spectrum of 5-phenyldipyrromethane (5e)

NH HN

Figure 5.4 : 13C NMR of spectrum 5

Figure 5.5: HRMS-mass of spectrum 5

273

C NMR of spectrum 5-phenyldipyrromethane (5e)

mass of spectrum 5-phenyldipyrromethane (5e)

Chapter 5

(5e)

(5e)

Chapter 5

274

5.7 Synthesis of expanded porphyrins Expanded porphyrins having a macrocycle larger than porphyrins have attracted considerable attention in light of their unique and fascinating optical, electrochemical, and coordination properties.48 As a result, a variety of expanded porphyrins have been prepared differing in ring size, ring connectivity, and hetero atom replacement.49 5.7.1 Synthesis of meso-aryl expanded porphyrins A solution of 5-(pentafluorophenyl)dipyrromethane and pentafluorobenzaldehyde in dichloromethane was treated with methane sulfonic acid or trichloroacetic acid for 2 h at 0°C followed by oxidation with DDQ gave the expanded porphyrins in good to modrate yields. Methanesulfonic acid (MSA) was found more suitable for ring size selective synthesis of meso-aryl expanded porphyrins when used at 0°C which allowed the formation of meso-aryl expanded porphyrins including porphyrin (9%), hexaphyrin (19%), octaphyrin (38%) and decaphyrin (15%), while the scrambling was observed at room temperature. Similar ring size selective synthesis of meso-aryl expanded porphyrins was also effected with trichloroacetic acid. Hexaporphyrin gave a characteristic soret at 566 and one Q band at 709 nm in UV-Visible spectrum. meso-Hexakis (pentafluorophenyl)-substituted [26]hexaphyrin( 1.1.1.1.1.1) is a planar rectangular macrocycle with a metallic luster in the solid state and a vivid purple color in solution.50,51 This expanded porphyrin can be regarded as a representative porphyrin homologue in terms of its planar structure and strong aromaticity. The 1H NMR spectrum of reveals a distinct diatropic ring current by displaying strongly shielded signals due to the inner β-and NH-protons and strongly deshielded signals due to the outer β-protons.

NH HN

FFF

FF FFF

FF

CHO

+DCM, MSA

N

NH N

HN

Ar

Ar

Ar

Ar

n7a. n = 37b. n = 57c. n = 7Ar = C6F5

5j

6

Scheme 5.20: Synthesis of expanded porphyrins

Chapter 5

275

N

N

NH N

N HN

F F

FF

F F

FF

F F

F

FF

F

F F

F

F

F

F

FF

F

FF

F

F

F

F

F

Figure 5.6: 1HNMR spectrum of 26-π Hexaphyrin (1.1.1.1.1.1) (7a)

Figure 5.7: UV-Visible spectrum of 26-π Hexaphyrin (1.1.1.1.1.1) (7a)

Chapter 5

276

5.7.2 Synthesis of aromatic core-modified porphyrins hexaphyrins Hexaphyrin (1.1.1.1.1.1) has been classified as a real homologue of porphyrin in terms of a conjugated cyclic π-system with an alternate arrangement of pyrrole rings and methine bridges. Hexaphyrins exhibit a regular structure with meso-substituted hexaphyrins, inverted hexaphyrin as aromatic and eight conformation hexaphyrin as nonaromatic52. The core modification by substitution of one or more nitrogen atom with oxygen, sulfur and selenium give rise the core modified porphyrins with modified electronic structure and properties. The condensation of core modified tripyrrane with sterically hindered aldehyde from the 16π dithiahexaphyrin and diselenahexaphyrin

Osuka and Anderson have independently reported a [2 + 2 + 2] condensation reaction of dipyrromethane with various aldehydes leading to the formation of desired hexaphyrins in addition to the porphyrins as the byproduct.53 Interstingly, Osuka and co-workers isolated a 26π aromatic planar hexaphyrin using protic acid as a catalyst, while Anderson and co-workers isolated a reduced form 28π nonaromatic hexaphyrin using a Lewis acid as the catalyst. Thus, it is clear that the synthetic method where the desired hexaphyrins can be isolated as a single product is lacking in the literature, and development of such a methodology leads to the isolation of hexaphyrin in better yields, making them amenable for further studies for various applications.

Aromatic core-modified hexaphyrins has been synthesized by the reaction of 2,5-bis[1-(4-tert-butyl-phenyl)-1-pyrrolomethyl]thiophene with pentafluorobenzaldehyde in presence of trifluoro acetic acid in dry dichloromethane under nitrogen atmosphere at room temperature for an one hr. After adding DDQ reaction mixture was refluxed for additional one hr and reaction mixture was cooled to room temperature and filtered on a basic alumina pad to get crude product as hexaphyrin. Crude hexaporphyrin was further chromatograph over basic alumina to give the pure hexaphyrin in 5-8 % yield. The structure of the compound was characterized by various spectroscopic data i.e. UV-Visible NMR IR and other spectroscopic data.

NHS

HN+

TFAD

F

FCHO

F

FF

8

Scheme 5.21: Synthesis

In UV-visible spectrum of expended porphyrin showed the two Q band at 710 and 770 nm and one soret at 571 nm (Figure

Figure 5.8: UV-Visible spectrum of aromatic core

5.7.3 Synthesis of sapphyrin and other expanded core modified porphyrins2,9-bis[1-(4-tert-butyl-phenyl)reaction of bisthiophene, n-BuLi and TMEDA in dry hexane under nitrogen atmospherefollowed by p-tert-butyl-benzaldehyde in anhydwas characterized by 1H NMR spectrum (

277

SN

N

SN

N

A, DCMDDQ

F

FF

F

F

FF

FFF

9

Synthesis of aromatic core-modified hexaphyrins

spectrum of expended porphyrin showed the two Q band at 710 and 770 Figure 5.8).

Visible spectrum of aromatic core-modified hexaphyrins (

and other expanded core modified porphyrins-hydroxymethyl]bisthiophene was synthesized by the

BuLi and TMEDA in dry hexane under nitrogen atmospherebenzaldehyde in anhydrous THF. Structure of the compound

H NMR spectrum (Figure 5.9).

Chapter 5

modified hexaphyrins

spectrum of expended porphyrin showed the two Q band at 710 and 770

modified hexaphyrins (9)

and other expanded core modified porphyrins was synthesized by the

BuLi and TMEDA in dry hexane under nitrogen atmosphere . Structure of the compound

NS

N

S

15

But

But

Bu

Bu

Figure 5.9: 1H NMR spectrum of bisthiophene

Sapphyrin has been synthesized by the reaction of pyrrolomethyl]thiophene with in presence of acidic ionic liquids in dry dichloromethane under nitrogen atmosphereroom temperature followed by DDQ oxidation gave the mixture of core modified

278

S

SN

1. Acidic ILs/CH2Cl22. DDQ.

+

Saphyrin X =

37

NHS

HNSS

HO OH+

But

But

ut

ut

S S

N

S

N+

But

But

But

But

Scheme 5.22

H NMR spectrum of 2,9-bis[1-(4-tert-butyl-phenyl)bisthiophene

Sapphyrin has been synthesized by the reaction of 2,5-bis[1-(4-tertpyrrolomethyl]thiophene with 2,9-bis[1-(4-tert-butyl-phenyl)-hydroxymethyl]bisthiophene in presence of acidic ionic liquids in dry dichloromethane under nitrogen atmosphereroom temperature followed by DDQ oxidation gave the mixture of core modified

Chapter 5

S

SN

= S, Se

38

But

But

phenyl)-hydroxymethyl]

tert-butyl-phenyl)-1-hydroxymethyl]bisthiophene

in presence of acidic ionic liquids in dry dichloromethane under nitrogen atmosphere at room temperature followed by DDQ oxidation gave the mixture of core modified

Chapter 5

279

expanded porphyrins which were purified by column chromatography. The structure of compounds were characterized by different spectroscopic data. Appearance of one soret at 506.64 nm and five Q bands at 580.34, 624.78, 672.0, 774.89 and 875.08 in UV-Visible spectrum of sapphyrin in chloroform. In 1H NMR spectrum of sapphyrin two singlet at -0.75 and 1.59 ppm were assigned for two inner thiophenic protons, and tert-butyl methyl protons six doublets at 7.73, 8.11, 8.29, 8.41, 8.88 and 9.98 ppm were assigned for aryl protons, β-pyrrolic protons and β-thiophenic protons respectively (Figure 5.10).

S S

NN

But

But

But

But

S

Figure 5.10: 1H NMR spectrum of core modified sapphyrin

5.8 Synthesis of 30π and 40π expanded porphyrinoids Porphyrins and expanded porphyrins represent model systems to understand the delocalization of π electrons in large cyclic conjugated systems. Electronic properties of such macrocycles are strongly dependent on their structural features and the nature of substituents.54 Invariably, such macrocycles tend to twist and adopt nonplanar conformations due to their flexible nature.55 Owing to this affinity for twisting, even 4n + 2π systems are devoid of aromatic features.56 To date, 34π core-modified octaphyrins are the largest planar expanded porphyrins to be characterized in the solid and solution states.57 Reaction of pyrrole with pentafluorobenzaldehyde generates a series of

Chapter 5

280

expanded porphyrins.2 Replace the pyrrolic units with other heterocycles such as thiophene/furan/selenophene can be used to generate core-modified porphyrinoids, which are structurally similar to annulenes.58

To the stirred solution of pentafluorobenzaldehyde and furan in 50 ml of dry dichloromethane, BF3.OEt2 was added under dark, and the resulting solution was stirred for 1h under nitrogen atmosphere. After adding FeCl3 solution was opened to air and stirred for two more hours. The reaction mixture was washed with water and passed through a short alumina column. Crude product was purified by column chromatography over silica gel (60-120 mess) eluting with chloroform/ petroleum ether 2:8 gave cyclco-hexa furan as first fraction and cyclco-octa furan (Scheme 5.23) as last fractions in 2% and 1% yield59 which were characterized by different spectroscopic data.

O

O

O O

O O

C6F5 C6F5

C6F5

C6F5

C6F5

C6F5

O

O O

O

OO

O O

C6F5

C6F5C6F5

C6F5

C6F5

C6F5

C6F5

C6F5

O

O O

O

C6F5

C6F5

C6F5

C6F5

O

CHOFF

FF

F

1. 1 equiv BF3.O(Et)2 CH2Cl22. FeCl3

+

20π 30π 40π

11 12

10

Scheme 5.23: Synthesis of 30π and 40π expanded porphyrinoids

In UV-Visible spectrum of 30π expanded porphyrinoid showed a strong absorption at 551 nm followed by a weaker band at 664 nm is due to their extensive conjugation. 1H NMR spectra tells a symmetrical structure for both 30π and expanded porphyrinoid and 40π and expanded porphyrinoid. In the case of 30π and expanded porphyrinoid, two singlets were observed at 7.91 and 2.52 ppm corresponding to an equal number of (six) proton (Figure 5.11). Two discrete singlets are possible only if three rings are inverted in an alternate

Chapter 5

281

fashion such that the protons of the inverted and the non inverted furan rings are different from each other. In 30π system, the protons toward the centre of the macrocycle experience diatropic ring current effects and are hence upfield shifted, whereas protons on the periphery are downfield shifted justifying the aromatic nature of the macrocycle.

O

O

O O

O O

C6F5 C6F5

C6F5

C6F5

C6F5

C6F5

Figure 5.11: 1H NMR spectrum of 30π expanded porphyrinoids (11)

O

O

O O

O O

C6F5 C6F5

C6F5

C6F5

C6F5

C6F5

Figure 5.12: UV-Visible spectrum of 30π expanded porphyrinoid (11)

Chapter 5

282

O

O

O O

O O

C6F5 C6F5

C6F5

C6F5

C6F5

C6F5

Figure 5.13: ESI-MS spectrum of 30π expanded porphyrinoid (11)

O

O O

O

OO

O O

C6F5

C6F5C6F5

C6F5

C6F5

C6F5

C6F5

C6F5

Figure 5.14: 1H NMR spectrum of 40π expanded porphyrinoid (12)

Similarly 40π system displayed two singlets protons at 9.06 and 5.80 ppm (expanded porphyrinoid exhibits absorptions at 535 nm and 498(sh) nm with no lowenergy absorptions (Figure 5.140π and expanded porphyrinoidan antiaromatic character as expected for a 4

Figure 5.15: ESI-MS spectrum of 40

Figure 5.16: UV-Visible spectrum of 40

283

displayed two singlets corresponding to equal number of (eight) protons at 9.06 and 5.80 ppm (Figure 5.14). In spite of its extended conjugation,

exhibits absorptions at 535 nm and 498(sh) nm with no low5.16). The lack of a red shift in the absorption spectrum for

and expanded porphyrinoid with respect to 30π and expanded porphyrinoidcharacter as expected for a 4nπ system.

MS spectrum of 40π expanded porphyrinoid (12)

Visible spectrum of 40π expanded porphyrinoid

Chapter 5

corresponding to equal number of (eight) ). In spite of its extended conjugation, 40π

exhibits absorptions at 535 nm and 498(sh) nm with no low-ed shift in the absorption spectrum for

and expanded porphyrinoid reveals

(12)

expanded porphyrinoid (12)

Chapter 5

284

5.9 Synthesis of 1,9-Bisformyl-5,5-dipropyldipyrromethane 5-ethyl-5-methyldipyrromethane was dissolved in 100 mL of DMF and cooled to 0°C. Next 2.5 equivalent POCl3 was added into the cooled solution60. After stirring for 4 h, the solution was made basic with concentrated aqueous NaOH (the effective solution pH = 11) and heated to reflux and held there for 2 h (Scheme 5.24). Finally, the reaction mixture was quenched with water, extracted with ethyl acetate, and dried over anhydrous Na2SO4. Purification via column chromatography on silica gel eluting with chloroform: methanol, (99:1) gave 13 in good yield and compound was characterized by different spectroscopic data.

NH HN

R1 R2

NH

OHC

HN

CHO

R1 R2

DMF/ POCl3

5a. R1 = R2 = CH3 5b. R1 = CH3 R2 = CH2CH35c. R1 = CH2CH2CH3 R2 =CH2CH2CH3

13a. R1 = R2 = CH3 13b. R1 = CH3 R2 = CH2CH313c. R1 = CH2CH2CH3 R2 =CH2CH2CH3

5 13

Scheme 5.24: Synthesis of 1,9-diformyl-5,5-disubtituted dipyrromethane

In 1H NMR spectrum of compound 1,9-bis-formyl-5,5-dipropyldipyrromethane triplet at 0.76 ppm was assigned for three methyl protons, a sharp singlet at 1.62 ppm was assigned for three methyl protons, a quartet at 2.10 ppm was assigned for two methylene protons, two multiplet at 6.20 and 6.82 ppm were assigned for four β-pyrrolic protons, a sharp singlet at 9.16 ppm was assigned for two –CHO group protons and finally a sharp singlet at 10.66 ppm was assigned for two pyrrolic proton (Figure 5.17). Formation of the title compound confirmed by 2,4-DNP test, in this test 2,4-dinitrophenylhydrazine react with aldehyde or ketones to gave a conjugate compound which shows pink or red colour on tlc due to increment of conjugation with title compound.

In 13C NMR spectrum of compound 1,9-bisformyl-5,5-dipropyldipyrromethane 13c showed total nine peaks. Four peak appeared at 8.77, 24.77, 32.98 and 40.53 ppm were assigned for methyl, methylene, and meso-carbon respectively and four peaks appeared at 109.34, 122.40, 132.40 and 147.14 ppm were assigned for β- pyrrolic and α- pyrrolic carbon and finally a peak appeared at 179.09 ppm was assigned for aldehydic group carbon (Figure 5.18).

Figure 5.17: 1H NMR spectrum of 1,9

Figure 5.18: 13C NMR spectrum of 1,9

285

H NMR spectrum of 1,9-bisformyl-5,5-dipropyldipyrromethane

C NMR spectrum of 1,9-bisformyl-5,5-dipropyldipyrromethane

Chapter 5

dipropyldipyrromethane (13b)

dipropyldipyrromethane(13b)

Chapter 5

286

5.10 Synthesis of 1-formyl 5,5-dimethyldipyrromethane To a stirred solution of 5,5-dimethyldipyrromethane in 10 ml of dry DMF cooled with ice-salt bath was added dropwise a solution of POCl3 in 2 mL of DMF under Ar. The mixture was stirred for 30 min at –10-0°C, and then allowed to warm to room temperature for 1.5 h (Scheme 5.25). The solution was then diluted with Et2O (50 mL) and extracted with water and made the solution basic with Na2CO3 solution. Left the solution overnight for precipitation, the yellow precipitate was filtered off and dried the crude product under reduced pressure. The crude product was purified by column chromatography on neutral alumina with chloroform as the eluent followed by filtration through a pad of silica gel washed with chloroform. Treating with pentane after an evaporation of most of the solvent gave of compound 1-formyl 5,5-dimethyldipyrromethane as cream-white crystals.

NH HNCHO

NH HNPOCl3/DMF

5a 14 Scheme 5.25: Synthesis of 1-formyl-5,5-dimethyldipyrromethane

Formation of the compound was characterized by different spectroscopic data. Primarily the formation of the compound was confirmed by 2,4-DNP test, 2,4-dinitrophenylhydrazine is often abbreviated to 2,4-DNP or 2,4-DNPH. A solution of 2,4-dinitrophenylhydrazine in a mixture of methanol and sulphuric acid is known as Brady's reagent. The reaction of aldehydes and ketones with 2,4-dinitrophenylhydrazine (Brady's reagent) as a test for the carbon-oxygen double bond. A bright orange or yellow precipitate shows the presence of the carbon-oxygen double bond in an aldehyde or ketone (Scheme: 5.26). This is the simplest test for an identification of aldehyde or ketone. In terms of mechanisms, this is a nucleophilic addition-elimination reaction. The 2,4-dinitrophenylhydrazine first adds across the carbon-oxygen double bond (the addition stage) to give an intermediate compound which then loses a molecule of water (the elimination stage).

Chapter 5

287

H2NHN

O2N

NO2OR1

RO2N

NO2NHNR1

R

R = DPM, R1 = H,15 16

Scheme 5.26: Diagrammatic representation of 2,4-dinitrophenylhydrazine test

On the other hand In 1H NMR spectrum of title compound (Figure 5.19) showed a sharp singlet at 1.67 ppm was assigned for six methyl proton, three multiplets at 6.07, 6.66 and 6.88 ppm were assigned for three β-pyrrolic protons, one α-pyrrolic proton and one β-pyrrolic proton. Finally three singlets at 8.19, 9.28 and 9.33 ppm were assigned for two pyrrolic –NH and one aldehydic proton respectively. Two peaks appeared at 3320 and 3284 cm-1 in IR spectrum of compound 1-formyl-5,5-dimethyldipyrromethane confirmed the presence of NH group in the title compound and a new peak appeared at 1617 cm-1 confirmed the introduction of formyl group in the parental molecule. Finally the formation of the compound was confirmed by 13C NMR spectrum. In 13C NMR spectrum of compound 1-formyl-5,5-dimethyldipyrromethane (Figure 5.20) showed two peaks 28.65, 35.74 ppm were assigned for methyl and meso carbon, four peaks at 104.62, 107.63, 108.10 and 117.70 ppm were assigned for β-pyrrolic carbon, another four peaks appeared at 122.32, 131.96, 136.78 and 149.12 ppm were assigned for α-pyrrolic carbon and finally a peak appeared at 178.61 ppm was assigned for formyl group carbon which confirmed the formation of 1-formyl 5,5-dimethyldipyrromethane.

NH HN

CHO

Figure 5.19 : 1H NMR spectrum of 1-formyl 5,5-dimethyldipyrromethane (14)

Chapter 5

288

NH HN

CHO

Figure 5.20: 13C NMR spectrum of 1-formyl 5,5-dimethyldipyrromethane (14)

5.11 Synthesis conjugated dipyrromethane in task specific basic ionic liquids The basic ILs have been emerged as promising basic catalyst in replacement of conventional homogeneous and heterogeneous basic catalysts due to their flexible, nonvolatile, noncorrosive, resistant to hydrolytic decomposition in nature and immiscible with many organic solvents. Moreover the acetate and hydroxyl functionalized basic ILs have been used for the synthesis of various heterocyclic molecules such as phthalocyanine. Hence the reaction of mono and diformyl dipyrromethane and active methylene compounds in the presence of basic ionic liquids for the synthesis of conjugated dipyrromethanes under ecofriendly conditions have been examined.

The reaction of 1-formyl-5,5-dimethyldipyrromethane and 1,9-bisformyl-5-ethyl-5-methyl-dipyrromethne in the presence of [bhyeda][OH-], [bmim][OH-], 2-Hydroxyethyldimethylammonium acetate, 2-Hydroxyethylammonium acetate gave the corresponding conjugate dipyrromethane in moderate to good yield.

Chapter 5

289

NH3C

H3CBu OH

NH3C

H3CH CH3COO

NH

HH CH3COO

NN BuH3C OH

CH2CH3OH

CH2CH3OH

CH2CH3OH

17

18

19

20

Figure 5.21: Structures of task specific ionic liquids

5.12 Synthesis of 1,9-bis-(-2-methylene-1,3-methylpyrimidine-2,4,6-trione)-

5-ethyl-5-methyl-dipyrromethane Genarally the aldehyde react with active methylene compound in presence of strong base such as piperidine, pyridine in organic solvent gave the conjugated product in good yield. Handling of these base and organic solvents were very difficult and hazardous, removal of these were also very difficult. Ionic liquids have been used as catalytic species and alternative solvents to replace the traditional solvents61. The ionic liquid [bhyeda][ OH-] was used as catalytic species and reaction medium under mild reaction conditions (Scheme 5.27). Generally, in all instances, the condensation of aldehyde and active methylene compound was proceeded at 60 °C to give the corresponding conjugated dipyrromethanes in good to excellent yields in the presence of ionic liquid [bhyeda][ OH-]. The reaction of 1,9-bisformyl-5-ethyl-5-methyldipyrromethane with 1,3-dimethylpyrimidine-2,4,6-trione at 60°C for appropriate time (table 5.2) in the presence of basic ionic liquid [hyeda][CH3COO-], [bhyeda][ OH-], [bmim][OH-] and [hyea][CH3COO-] gave correspoding conjugated dipyrromethane in 92%, 94%, 89%, 83% yields respectively.

Chapter 5

290

N N

O O

O

N

NO

O

O

N

NS

O

O

O

O

R1 =

NH HNCHOOHC

IL, 60 °C NH HNR2R1

R2 =

21

21a.

21b.

21c.

Scheme 5.27: Synthesis of 1,9-bis-(-2-methylene-1,3-methylpyrimidine-2,4,6-trione)-

5-ethyl-5-methyl-dipyrromethane However [hyeda][CH3COO-], [bmim][OH-] and [hyea][CH3COO-] were found not so effective as [bhyeda][ OH-], in which comparable yields of dipyrromethane (Table 5.2). The better yield of conjugated dipyrromethane were observed in the presence of [bhyeda][OH-] basic ionic liquid at 60 °C for 35 min. The neutral ionic liquid [bmim][Br-] was not effective ionic liquid for the synthesis of conjugated dipyrromethane at refluxing temperature as well as the ionic liquid such as [hyeda][CH3COO-], [bhyeda][ OH-], [bmim][OH-] and [hyea][CH3COO-] were also not gave the conjugated dipyrromethane at room temperature. Moreover the reaction workup is easy, the addition of water to the reaction mixture, precipitate out the desired product.

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Table 5.2: Reaction of mono and diformyl dipyrromethane with active methylene compounds in presence of ILs under different reaction conditionsa

Entry bBasic ILs Reaction Temp.

Reaction Time (min)

Product Yieldc

1d [hyeda][CH3COO-] rt 120-180 0 0

2 [hyeda][CH3COO-] 60°C 40 21a 92

3 [bmim][Br-] 60°C 10-60 0 0

4 [bhyeda][ OH-] 60°C 35 21a 94.0 5 [bmim][OH-] 60°C 40 21a 89

6 [hyea][CH3COO-] 60°C 45 21a 83

7 [hyeda][CH3COO-] 60°C 30 21b 94.2

8 [bhyeda][ OH-] 60°C 30 21b 96.0

9 [bmim][OH-] 60°C 40 21b 90 10 [hyea][CH3COO-] 60°C 45 21b 86

11 [hyeda][CH3COO-] 60°C 25 21c 93.5

12 [bhyeda][ OH-] 60°C 25 21c 94.0

13 [bmim][OH-] 60°C 25 21c 88.9 14 [hyea][CH3COO-] 60°C 30 21c 84.7

15 [hyeda][CH3COO-] 60°C 30 22a 95.5

16 [bhyeda][ OH-] 60°C 25 22a 96.0

17 [bmim][OH-] 60°C 45 22a 93.0

18 [hyea][CH3COO-] 60°C 40 22a 90.5 19 [hyeda][CH3COO-] 60°C 30 22b 97.3

20 [bhyeda][ OH-] 60°C 30 22b 98.5

21 [bmim][OH-] 60°C 45 22b 91.5

22 [hyea][CH3COO-] 60°C 45 22b 90.0 aReaction conditions: aldehyde (10 mmol), active methylene compound (20 mmol or 10 mmol), ILs (5 ml), bIonic liquid were prepared by usual method. cIsolated yield.

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The structure of compound 1,9-bis-(-2-methylene-1,3-methylpyrimidine-2,4,6-trione)-5-ethyl-5-methyl-dipyrromethane was confirmed by 1H NMR, 13C NMR spectroscopic analysis. In 1H NMR spectrum of title compound 1,9-bis-(-2-methylene-1,3-methylpyrimidine-2,4,6-trione)-5-ethyl-5-methyldipyrromethane (Figure 5.22) a triplet at 0.91 ppm was assigned for three methyl protons, a sharp singlet at 1.85 ppm was assigned for three methyl protons, a quartet at 2.23 ppm was assigned for two methylene protons, and a another sharp singlet at 3.35 ppm was assigned for three methyl protons attached to the nitrogen atom, two multiplet at 6.42 and 7.08 ppm were assigned for four β-pyrrolic protons, and finally two more singlet were found at 8.22 and 13.56 ppm were assigned for two olifinic protons and two pyrrolic protons. Formation of the compound was confirmed by 1H NMR spectroscopic data; a additional peak at 3.35 ppm for three methyl protons and shift in the pyrrolic protons by 2.90 ppm was observed which confirmed the formation of titled compound.

NH HN

N N N N

OO O O

OO

Figure 5.22: 1H NMR spectrum of 1,9-bis-(-2-methylene-1,3-dimethylpyrimidine-2,4,6-trione)-5-ethyl-5-methyldipyrromethane (21a)

In 13C NMR spectrum of compound 1,9-bis-(2-methylene-1,3-dimethylpyrimidine-2,4,6-trione)-5-ethyl-5-methyldipyrromethane (Figure 5.23) showed total thirteen peaks at 8.98, 22.80, 28.79, 33.34, 41.59, 104.73, 113.14, 129.18, 130.81, 142.12, 150.65, 163.33 and

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163.75 ppm. By which of five peaks were assigned for methyl, methylene, meso and methyl carbons attached to the nitrogen atom respectively. Remaining eight peaks were assigned for β-pyrrolic, quaternary, α- pyrrolic, olifinic and carbonyl group carbons respectively.

NH HN

N N N N

OO O O

OO

Figure 5.23: 13C NMR spectrum of 1,9-bis-(-2-methylene-1,3-methylpyrimidine-

2,4,6-trione)-5-ethyl-5-methyl-dipyrromethane (21a)

Figure 5.24: UV-visible spectrum of 1,9-bis-(-2-methylene-1,3-methylpyrimidine-

2,4,6-trione)-5-ethyl-5-methyl-dipyrromethane in DMSO (21a)

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5.12.1 Anion sensing by 1,9-bis-(-2-methylene-1,3-methylpyrimidine-2,4,6-trione)-5-ethyl-5-methyl-dipyrromethane (21a) 1,9-bis(2’-methylene-1,3-diphenyl-2-thioxopyrimidine-4,6-dione)-5-ethyl-5-methyl-dipyrromethane, (21b) 1,9-bis(2’-methylene-indane-1,3-dione)-5-ethyl-5-methyl-dipyrromethane (21c)

The naked eye detection experiment was carried out in DMSO by addition of the corresponding anions (5×10-6 to 5×10-5) to the solution of receptors 21a, 21b and 21c (5×10-6 M). The addition of fluoride anions into the DMSO solution of receptor 21a, 21b and 21c resulted in yellow to dark yellow and red colour change and suggesting that F- interacts with the receptors 21a 21b and 21c. On the other hand the colour change of receptor 21c was much more sensitive to fluoride acetate dihydrogen phosphate than receptor 21a and 21b. One tenth equivalent of fluoride acetate dihydrogen phosphate were enough to induce an observable colour change from yellow to orange in 21c receptor. The most remarkable effect of color change induced in receptor 21a, 21b and 21c towards acetate and dihydrogen phosphate. Among three anions the noticeable colour change was found with acetate and dihydrogen phosphate. Receptor 21a and 21b did not give a noticeable colour response towards acetate, however on addition of excess dihydrogen phosphate color of the solution 21a and 21b changed from yellow to dark yellow. In contrast, the addition of 21c in the presence of dihydrogen phosphate and acetate turned orange at a low anion concentration (5×10-5

M) figure 5.27. All the receptors were found to be insensitive to addition of large excess (5×10-2) of chloride, bromide, iodide and hydrogen solution anions.

Figure 5.25: Colour change of receptor 21a (5.0×10-6 M) in DMSO upon addition

of tetrabutyl ammonium anions (5.0×10-4 M)

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Figure 5.26: Colour change of receptor 21a (5.0×10-6 M) in DMSO upon addition

of tetrabutyl ammonium anions (5.0×10-4 M)

Figure 5.27: Colour change of receptor 21a (5.0×10-6 M) in DMSO upon addition

of tetrabutyl ammonium anions (5.0×10-4 M) 5.14.2 UV-Visible spectroscopy The complexation studies of compound 21a-21c were carried out with the help of UV-Visible spectroscopy in DMSO at room temperature. Titrations were performed by the adding of 20µl of stock solution (5×10-5M) of anionic guest (F) to the investigated the derivatives 21a-21c (5×10-5M). UV-Visible spectra of 21a showed a characteristic absorption maximum at 394 and 438nm. On addition of fluoride, acetate and dihydrogen phosphate anion in DMSO (5×10-5) the characteristic absorption peaks of 21a (5×10-6) at 394 nm increase gradually and peak at 438 nm increased with red sift 4-6 nm respectively. At the same time two clear isobestic point at 414 and 461nm were observed for receptor 21a which indicate that there is a balance in the solution and the complex had been formed between host and guest.

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21a/ F- 21a/ AcO-

21a/PO4

3- 21a/Cl-

Figure 5.28: UV-Visible titration of 21a (5×10-6M) with anions (5×10-5 -5×10-6M) The UV-Visible spectra of 21a change dramatically on the addition of fluoride, acetate and dihydrogen phosphate anions. Figure 5.20 shows the absorption spectra of 21b in presence of fluoride, acetate and dihydrogen phosphate anions. On addition of fluoride, acetate and dihydrogen phosphate anion in DMSO (5×10-5) the characteristic absorption peaks of 21b (5×10-6) at 394 nm increase gradually and peak at 438 nm increased with red sift 4-6 nm respectively. At the same time two isobestic points at 414 and 461nm were observed for receptor 21a which indicate the complex had been formed between host and guest.

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21b/PO4- 21b/AcO-

21b/F- 21b/other anions

Figure 5.29: UV-Visible titration of 14b (5×10-6M) with anions (5×10-5 -5×10-6)

Figure 5.30: UV-Visible titration of 21b (5×10-6M) with different anions (5×10-5 -5×10

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21c/ PO4-3 21c/AcO-

21c/F- 21c/other anions

Figure 5.31: UV-Visible titration of 21c (5×10-6M) with different anions (5×10-5 -5×10-6) 5.13 Synthesis of 5,5-dimethyldipyrromethane-2-methylene-1,3-dimethyl

pyrimidine-2,4,6-trione (22a) The 1-formyl 5,5-dimethyldipyrromethane and active methylene compound 1,3-dimethylpyrimidine-2,4,6-trione were stirred in [bhyeda][OH-] ionic liquid (5 mL) at 60°C temperature for appropriate time in (Table 5.2). After completion of the reaction as indicated by the TLC, the mixture was poured in cold water and solid was filtered off. The crude solid was washed with several portion of water and dried under reduced pressure to afford the conjugated coloured solid compound, which was further purified by column chromatography over neutral alumina using chloroform as eluting solvent.

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The rest of the viscous ionic liquid was further dried under reduced pressure to retain its activity and use it for next runs.

NH HNCHO

N N

O O

O

NH HNR1

N

NO

O

O

N

NS

O

OO

O

R1 =

IL, 60 °C 22

22a

22b

22c

Scheme 5.28: Synthesis of 5,5-dimethyldipyrromethane-2-methylene-1,3-

dimethylpyrimidine-2,4,6-trione Structure of the compound was confirmed by different spectroscopic data. Two strong peaks appeared at 3294 and 1654 cm-1 in IR spectrum of compound 5,5-dimethyldipyrromethane-2-methylene-1,3-dimethylpyrimidine-2,4,6-trione (22a) confirmed the NH and C=O group in the molecule. In 1H NMR spectrum of title compound (Figure 5.32) a sharp singlet appeared at 1.71 ppm was assigned for six meso-methyl protons and another sharp singlet at 3.25 ppm was assigned for six methyl protons attached to the nitrogen atom. Four multiplets at 6.09, 6.26, 6.68 and 6.97 ppm were assigned for four β-pyrrolic protons and one α-pyrrolic proton respectively. A sharp singlet at 8.06 was assigned for one formyl group proton and two singlets appeared at 8.26 and 13.27 ppm was assigned for two different pyrrolic NH protons.

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On the other hand the additional peaks in carbon NMR spectrum of compound 5,5-dimethyldipyrromethane-2-methylene-1,3-dimethylpyrimidine-2,4,6-trione confirmed the formation of the title compound. In carbon NMR spectrum of compound 5,5-dimethyldipyrromethane-2-methylene-1,3-dimethylpyrimidine-2,4,6-trione showed the total fifteen peaks (Figure 5.32). Three peaks appeared at 28.08, 29.67 and 36.45 ppm were assigned for methyl, N-methyl and meso carbon. Eight peaks appeared at 103.58, 104.77, 108.19, 112.78 and 117.76, 128.68, 131.51, 136.34 ppm were assigned for eight β-pyrrolic carbon and α-pyrrolic carbon. Remaining four peaks appeared at 141.57, 151.66, 155.45 and 163.59 ppm were assigned for oliphinic carbon, quaternary carbon and two peaks for carbonyl carbon respectively. Finally the formation of title compound was confirmed by UV-visible spectrum, in UV-visible spectrum of 5,5-dimethyldipyrromethane-2’-methylene-1,3-dimethylpyrimidine-2,4,6-trione showed a absorption at 426.51 nm confirmed the formation of title compound (Figure 5.33).

NH HN

N N

O

OO

Figure 5.32: 13C NMR spectrum of 5,5-dimethyldipyrromethane-(2’-methylene-

1,3-dimethylpyrimidine-2,4,6-trione) (22a)

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NH HN

N N

O

OO

Figure 5.33: 13C NMR spectrum of 5,5-dimethyldipyrromethane-(2’-methylene-

1,3-dimethylpyrimidine-2,4,6-trione) (22a)

NH HN

N N

O

OO

Figure 5.34: UV-Vis. spectrum of 5,5-dimethyldipyrromethane-(2’-methylene-1,3-

dimethylpyrimidine-2,4,6-trione) in DMSO (22a)

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5.13.1 Anion sensing by 5,5-dimethyldipyrromethane-(2’-methylene-1,3-dimethylpyrimidine-2,4,6-trione) (22a) 5,5-dimethyldipyrromethane-(2’-methylene-indane-1,3-dione (22b)

The naked eye detection experiment was carried out in DMSO by addition of the corresponding anions (5×10-6 to 5×10-3) to the solution of receptors 22a, and 22b (5×10-6 M) at room temperature. The addition of fluoride anions into the DMSO solution of receptor 22a and 22b resulted in yellow to dark yellow colour change. While the addition of other basic anions like phosphate and acetate along with chloride, bromide, hydrogen sulfate and iodide (5×10-2 M)did not give any noticeable colour response, suggesting that fluoride interacts with the receptor 22a and 22b more tightly due to its higher electronegativity and smaller size compared to the other halides (Figure 5.35).

Figure 5.35: Colour change of receptor 22a (5.0×10-6 M) in DMSO upon addition

of tetrabutyl ammonium anions (5.0×10-4 M)

5.13.2 UV-Visible spectroscopy The complexation studies of compound 22a and 22b were carried out with the help of UV-Visible spectroscopy in DMSO at room temperature. Titrations were performed by the adding of 20µl of stock solution (5×10-5M) of anionic guest (F) to the investigated the derivatives 22a-22b (5×10-6M). UV-Visible spectra of 22a showed a characteristic absorption maximum at 435. On addition of fluoride anion in DMSO (5×10-5) the characteristic absorption peaks of 22a (5×10-6) at 435 nm gradually increase (Figure 5.36). At the same time a clear isobestic point at 426 was observed for receptor 22a

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which indicate that there is a balance in the solution and the complex had been formed between host and guest.

The absorbance changes of receptor solution upon addition of fluoride at 435 nm. Similar phenomenon was recognized with chloride, however, the addition of bromide, iodide, and dihydrogen phosphate did not cause any significant spectral change even when a high excess of anion was employed, indicate that these anions form no (or very weak) complex with 22a.

22a/ F- 22a/ Cl-

22a/AcO- 22a/ PO4

-3

Figure 5.36: UV-Visible titration of 22a (5×10-6M) with different anions (5×10-5 -5×10-6)

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22b/ F- 22b/ Cl-

22b/AcO- 22b/ PO4

-3

Figure 5.37: UV-Visible titration of 22b (5×10-6M) with different anions (5×10-5 -5×10-6)

5.14 Non-covalent interactions with sapphyrins and related expanded

porphyrinoids The protonated sapphyrins are effective anion receptors62. A fluoride atom was found inside the sapphyrin core was hydrogen-bonded with all five nitrogens. The two chloride anions are apparently too large to be accommodated within the sapphyrin plane. They are thus bound to opposite faces of the diprotonated sapphyrin macrocycle via hydrogen bonds. In dichloromethane solution, The relative absence of quenching effects in the fluoride complex interacting strongly with the core NHs of sapphyrin.63 The presence of sapphyrin enhance the transport of the fluoride anion through the

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organic phase.64 Several covalently linked sapphyrin dimers, were prepared in the hope of creating a ditopic receptor for dianions such as dicarboxylates.65 Further evidence for carboxylate anion recognition came in the case of sapphyrins that contain appended carboxylic acid groups. The presence of these ionizable appendages leads to the formation of tightly held dimers, in which the core of each sapphyrin becomes protonated and associates with the anionic conjugate base “tail” of its partner.66 5.14.1 Study of non-covalent interactions of 30π and 40π expanded porphyrinoid

with fullerene and naphthalene 5.14.1.1 UV-Visible titrations of 30π expanded porphyrinoid with fullerene The absorption spectroscopic titration of 30π expanded porphyrinoid with C60 (fullerene) was performed in toluene at room temperature. Titrations were performed by the addition aliquots of 20 µL of stock solution (5×10-5 M) of guest (fullerene). Cyclohexa furan gives characteristic absorption maxima at 533 nm in a preliminary experiment, the addition of fullerene guest into toluene solution of cyclohexa furan, the absorption peak gradually decreases with bathochromically shifting 2-3 nm. A new peak at 406 nm was appeared, which was the characteristic peak of fullerene (Figure 5.38). The gradual decrease of peak at 433 nm is due to the π-π interaction of fullerene and 30π expanded porphyrinoid in solution and 1:1 complex was formed confirmed by Job’s plot.

O

O

O O

O O

C6F5 C6F5

C6F5

C6F5

C6F5

C6F5

Figure 5.38: UV-Visible absorption studies of 30π expanded porphyrinoid (5×10-7 M)

with C60 (5×10-5 M) in toluene (9)

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5.14.1.2 UV-Visible titrations of 30π expanded porphyrinoid with naphthalene The absorption spectroscopic titration of 30π expanded porphyrinoid with naphthalene (5×10-5 M) and other aromatic hydrocarbon were performed in chloroform and toluene at room temperature. Titrations were performed by the addition aliquots of 20 µL of stock solution (5×10-5 M) of guest (naphthalene). Cyclohexa furan gives characteristic absorption maxima at 554 nm in a preliminary experiment, the addition of naphthalene guest into chloroform solution of cyclohexa furan, the absorption peak gradually decreases with bathochromically shifting 2-3 nm. A new characteristic peak of fullerene at 406 nm was observed (Figure 5.39 The gradual decrease of peak at 554 nm is due to the π-π interaction of naphthalene and 30π expanded porphyrinoid in solution and 1:1 complex was formed confirmed by Job’s plot

OO

O

OO

O

C6F5

C6F5C6F5 C6F5

C6F5

C6F5

Figure 5.39: UV-Visible absorption studies of 30π expanded porphyrinoid (5×10-6 M)

with naphthalene (5×10-5 M) in toluene (11) 5.14.1.3 UV-Visible titrations of 40π expanded porphyrinoid and fullerene The absorption spectroscopic titration of 40π expanded porphyrinoid with C60 fullerene was performed in toluene at room temperature. Titrations were performed by the addition aliquots of 20 µL of stock solution (5×10-5 M) of guest (fullerene). Cycloocta

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furan gives characteristic absorption maxima at 537 nm and 498 nm in a preliminary experiment, the addition of fullerene guest into toluene solution of cycloocta furan, the absorption peak bathochromically decreases, and the presence of three isobestic points were observed at 417, 583 and 621 nm. A new characteristic peak of fullerene at 406 nm was observed (Figure 5.40). The gradual decrease of peak at 537 nm is due to the π-π interaction of fullerene and 40π expanded porphyrinoid in solution.

OO O

OOO

O OC6F5

C6F5C6F5

C6F5

C6F5

C6F5

C6F5

C6F5

Figure 5.40: UV-Visible absorption studies of 40π expanded porphyrinoid (5×10-6 M)

with C60 (5×10-5 M) in toluene (12) 5.15 Conclusion A convenient and one-pot reaction of pyrrole, aromatic aldehydes, aliphatic ketones catalyzed by diols for the preparation of meso substituted dipyrromethanes in different organic solvent. The reaction procedure is simple and cleaner reaction, easy workup makes this protocol practical and economically attractive. The reaction of acetone and aldehyde with pyrrole in presence of catalytic amount of diol “which was synthesized by the reaction of thiophene with n-butyllithium and TMEDA in dry hexane at reflux temperature gave the dilithiosalt of thiophene followed by 4-nitroacetophenone to gave corresponding novel diol in moderate to good yield” in dichloromethane at room temperature gave the 5-substituted dipyrromethane in moderate to good yield. Further

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the reaction of 5-pentafluorophenyldipyrromethane with pentafluorobenzaldehyde in dichloromethane in presence of methane sulfonic acid followed by oxidation with DDQ gave the hexaphyrin in modrate yields. The 30 and 40π expanded porphyrinoids were synthesized by the reaction of pentafluorobenzaldehyde with furan in dichloromethane in presence of BF3.OEt2 at room temperature under nitrogen atmosphere followed by oxidation with FeCl3. Non-covalent interactions of 30 and 40π expanded porphyrinoids with naphthalene and fullerene were carried out by UV-Visible spectroscopic titration in toluene at room temperature.

Core modified sapphyrin has been synthesized by the reaction of 2,5-bis[1-(4-tert-butyl-phenyl)-1-pyrrolomethyl]thiophene with 2,9-bis[1-(4-tert-butyl-phenyl)-hydroxymethyl]bisthiophene in presence of acidic ionic liquids in dry dichloromethane under nitrogen atmosphere at room temperature followed by DDQ oxidation. Their non – covalent interactions with anion like fluoride were examined by UV-Visible spectroscopic techniques.

The UV-visible spectra of core modified porphyrin gives a peak at 436 nm. Upon addition of the solution of fullerene the absorption of peak gradually decrease with bathochromatic shift by 20-22 nm. The bathochromatic shift was also observed with significant broadening. At the same time two isobestic points at 417 and 446 nm were observed. The gradual decrease of peak at 437 nm is due to the π-π interaction of fullerene and core modified N2S2 porphyrin expanded porphyrinoid in solution. The formation of 1:1 complex between the N2S2 porphyrin with fullerene were confirmed by UV-Visible spectroscopy.

Furthermore the reaction of 5,5-dimethyldipyrromethane and quantitative amount of Vilsmeier Reagent gave the 1-formyl-5,5-dimethyldipyrromethane and 1,9-bisformyl 5,5’-disubstituted dipyrromethane in quantitative yield. Further the reaction of formyldipyrromethane and active methylene compound such as 1,3-dimethylpyrimidine-2,4,6-trione, indane-1,3-dione and 1,3-diphenyl-2-thioxapyrimidine-4,6-dione in presence of basic ionic liquid gave the conjugated dipyrromethane in high yield. Non-covalent interactions of conjugated dipyrromethane with different anions were carried out by UV-Visible spectroscopic titration in DMSO at room temperature. The formation of 1:1

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complex between the conjugated dipyrromethane with fluoride and acetate anions were also confirmed by UV-Visible spectroscopy. 5.16 Experimental 5.16.1 Materials and Methods All melting points are uncorrected and expressed in degree centigrade and were recorded on Thomas Hoover Unimelt capillary melting point apparatus. The infrared spectra were recorded on Perkin-Elmer FT-2000 spectrometer and νmax are expressed in cm-l. 1H NMR was recorded on Jeol-delta-400 spectrometer using tetramethylsilane (TMS) as an internal standard and chemical shifts (δ) are expressed in ppm and coupling constant values (J) are in Hz. ESI-MS were recorded by LC-TOF (KC-455) mass spectrometer of Waters. Infrared spectra were recorded on Perkin-Elmer FT-IR model 9 spectrophotometer. The organic solvents were dried and distilled prior to their use. Reactions were monitored by precoated TLC plates (Merck silica gel 60F254). Silica gel (60-120 mesh) was used for column chromatography. The starting materials such as pyrrole, thiophene, furan, acetone, acetophenone, mono functional acetophenone, benzaldehyde, pentafluorobenzaldehyde, mesitaldehyde, tolualdehyde, 4-methoxybenzaldehyde, TMEDA, n-butyl lithium, 2-aminoethanol, imidazole, dimethyl aminoethanol and phosphoryl chloride were purchased from Spectrochem Pvt. Ltd, India and Sigma-Aldrich Chemicals Pvt. Ltd., USA. The pyrrole was distilled prior to use and the solvents used were of analytical reagent grade. The compounds synthesized were separated by column chromatography using neutral alumina, silica gel and characterized by melting points, 1H NMR, 13C NMR, IR and ESI-MS techniques. 5.16.2 Synthesis of diols from substituted acetophenone and benzaldehyde 5.16.2.1 Synthesis of 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)methyl]thiophene

(2d) Thiophene (1.3 g, 16 mmol) was added to a solution of n-BuLi (21 mL of 1.6 M in hexanes, 34 mmol) and TMEDA (5.4 mL, 36 mmol) in 50 mL of hexanes under an Ar atmosphere. The reaction mixture was heated at reflux for 1 h, cooled to ambient

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temperature, and transferred via a cannula to a pressure-equalizing dropping funnel. This dilithiothiophene suspension was then added dropwise to a solution of 4-nitroacetophenone (5.2 gm, 32 mmol) in 50 ml of anhydrous THF cooled to 0°C, which had been degassed with Nitrogen gas for 15 min. After the addition was complete, the mixture was warmed to ambient temperature, 20 mL of NH4Cl (aqueous 1 M solution) was added, and the organic phase was separated. The aqueous phase was extracted with dichloromethane (4 × 50 mL). The combined organic extracts were washed with water (3 × 50 mL) and brine (300 mL), dried over Na2SO4, and concentrated to give yellow oil. The crude product was precipitated by the slow addition of hexanes to crude solution of 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)methyl]thiophene to give 3.0 g (24%) of 2,5-bis[(1-(4-nitrophenyl-1-hydroxymethyl)methyl]thiophene as white amorphous powder. Recrystallization from ethyl acetate hexane 9:1 v/v gave white crystal.

Physical state: white solid. Rf: 0.39 (5:5, CHCl3: MeOH, v/v) Yield: 3.00 gm (24 %) mp: 50-52 °C IR (KBr pellet, cm-1): 1H NMR (400MHz, CDCl3, 25˚C) δ = 1.90 (s, 6H, -CH3) 2.51 (br, s, 2H, CHOH) 6.64 (d, J= 4.4 Hrz 2H, β-thiophene) 7.24 (d, J = 8.7 Hrz 4H, Ar-H) 7.33 (d, J = 8.8 Hrz 4H, Ar-H) 13C NMR (100MHz, CDCl3, 25˚C) δ = 45.25 (CH3), 74.31 (meso-C), 123.95 (β-thiophenic-C), 129.55, 130.48 (aryl-C), 140.71(α-thiophenic-C), 147.14, 150.49 (Cq). 5.16.3 Synthesis of diol catalysed synthesis of dipyrromethanes (5) 5.16.3.1 Synthesis of 5-(phenyl)dipyrromethane (5e) Pyrrole (1.0 mL, 14.4 mmol) and benzaldehyde (1.46 mL, 7.2 mmol) were taken in CH2Cl2 (5 mL). Diol (10%,w/w) was added to the reaction mixture, which was stirred at room temperature for 24h. The reaction progress was monitored by thin layer chromatography (TLC). After the completion of reaction, the solvent was removed

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under reduced pressure and crude product, was subjected to column chromatography over silica gel (60-120 mess) eluting with petroleum ether-chloroform (8:2, v/v) to afford pure 5-(phenyl)dipyrromethane. Further elution of the column with chloroform-methanol (9:1, v/v) gave the catalyst. The above general method is used for the synthesis of different 5,5’-disubstituteddipyrromethanes and 5-substituted dipyrromethane in good to excellent yield. Compound 5,5’-dimethyldipyrromethane and 5-ethyl-5-methyldipyrromethane were synthesized by this procedure and data were match with reported literature value.

Physical state: white solid. Rf : 0.47 (1:1 chloroform: hexane, V/V) mp: 100-101 °C. IR (KBr pellet, cm-1): 3343, 3057, 1457, 1258, 1095, 1114, 1026, 738, 725. 1H NMR (400MHz, CDCl3, 25˚C) δ = 5.45 (s, 1H, CH), 5.93 (s, 2H, β-pyrrolic-CH), 6.18 (m, 2H, β-pyrrolic-CH), 6.66 (m, 2H, α-pyrrolic-CH), 7.22 (m, 5H, Ar-H), 7.82 (s 2H, NH) 13C NMR (100MHz, CDCl3, 25˚C) δ = 43.84, (meso-C), 107.04, 108.29 (β-pyrrolic-C), 117.19, 126.88 (α-pyrrolic-C), 128.33, 128.55 (Ar-C), 132.47, 142.02 (Cq). 5.18.3.2 Synthesis of 5,5-dimethyldipyrromethane (25a) Acetone (15.0 mmol, 1.0 ml) and pyrrole (30.0 mmol, 2.07 ml) were taken and rest of procedure same as 5e

Physical state: white solid. Yield: 1.34 gm mp: 55 ºC (lit67 mp 54-56 ºC) Rf: .40 (1:1 CHCl3: hexane, v/v), IR (KBr, cm-1): 3429, (-NH) 2979 (-CH3), 1554, 1445, 1025, 720 cm-1

1H NMR (400MHz, CDCl3, 25 ˚C) δ = 1.61, (s, 6H, -CH3), 5.91 (d, J = 2.9 Hz, 2H, β-pyrrolic CH), 6.10 (m, 2H, β-pyrrolic CH), 6.57 (d, J = 2.2 Hz 2H, α-pyrrolic CH), 7.62 (br s, 2H, NH). 13C NMR (100MHz, CDCl3, 25 °C) δ = 29.26 (-CH3), 35.26 (meso-C), 103.71, 107.62 (β-pyrrrolic-C), 117.07, 139.07 (α-pyrrrolic-C).

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5.16.3.3 Synthesis of 5-ethyl-5-methyldipyrromethane (5b) Pyrrole (33.0 mmol, 2.17 ml) and 2-butanone (15.0 mmol, 1.35 ml) rest of the procedure was same as 5e

Physical state: brownish solid, Rf : 0.40 (1:1 CHCl3: pet ether, v/v) Yield: 1.4 gm mp: 102 ºC, IR (KBr, cm-1): 3348 (-NH), 2931 (-CH3) cm-1 1H NMR (400MHz, CDCl3, 25 ˚C) δ = 0.77 (t, 3H, -CH3), 1.53 (s, 3H, -CH3), 1.97 (q, 2H, -CH2), 6.10 (m, 4H, β-pyrrolic -CH), 6.56 (d, J = 2.2 Hz, 2H, α-pyrrolic CH) 7.56 (br s, 2H, pyrrolic-NH) 13C NMR (100MHz, CDCl3, 25 ˚C) δ = 8.77 (-CH3), 25.51 (-CH3), 33.43 (-CH2), 39.20 (meso-C), 104.65, 107.44 (β-pyrrolic, -C), 116.96, 138.63 (α-pyrrolic, -C). 5.16.3.4 Synthesis of 5,5’-dipropyldipyrromethane (5c) Pyrrole (33.0 mmol, 2.17 ml) and 4-heptanone (15.0 mmol, 1.71 ml) were taken and rest of the procedure was same as 5e

Physical state: white solid Rf : 0.52 (1:1 chloroform: hexane, V/V) mp: 60 °C IR (KBr pellet, cm-1): 3363, 2928, 2845, 1093, 1118, 721. 1H NMR (400MHz, CDCl3, 25˚C) δ = 0.81 (t, 6H, CH3), 1.06 (m, 4H, CH2), 1.84 (t, 4H, CH2), 6.07 (m, 4H, β-pyrrolic-CH), 6.57 (m, 2H, β-pyrrolic-CH), 7.62 (brs, 2H, NH) 13C NMR (100MHz, CDCl3, 25˚C) δ = 14.48 (CH3), 17.00 (CH2), 39.68 (CH2CH2), 42.59 (meso-C), 105.51, 107.16 (β-pyrrolic-C), 116.84, 137.31 (α-pyrrolic-C). 5.16.3.5 Synthesis of 5-methyl-5-phenyldipyrromethane (5f) Acetophenone (15.0 mmol, 1.80 ml) and pyrrole (30.0 mmol, 2.07 ml) were taken and rest of the procedure same as 5e

Physical state: white solid Rf : 0.52 (1:1 CHCl3: hexane, v/v)

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Yield: 1.5 gm (84 %), mp: 106 ºC IR (KBr, cm-1): 3375 (-NH) 2942 (-CH3) 1H NMR (400MHz, CDCl3, 25˚C) δ = 2.05 (s, 3H, -CH3), 5.97 (d, 2H, β-pyrrolic CH) 6.13 (m, 2H, β-pyrrolic CH) 6.67 (d, J = 2.2 Hz 2H, α-pyrrolic CH) 7.12 (m, 5H. Ar-H), 7.37 (br s, 2H, NH). 5.16.3.6 Synthesis of 5-(4-methoxyphenyl)dipyrromethane (5g) The 4-methoxybenzaldehyde (15.0 mmol, 2.0 gm) and pyrrole (30.0 mmol, 2.07 ml) were taken and rest of the procedure same as 5e

Physical state: white solid Rf : 0.37 (1:1 chloroform: pet. Ether, V/V) mp: 98-99 °C. IR (KBr pellet, cm-1): 3345, 3092, 1610, 1513, 1460, 1255, 1176, 1111, 1032, 843, 737, 726 1H NMR (400MHz, CDCl3, 25˚C) δ = 3.89 (s, 3H, OCH3), 5.50 (s, 1H CH), 6.01 (s, 2H, β-pyrrolic-CH), 6.25 (m, 2H, β-pyrrolic-CH), 6.76 (m, 2H α-pyrrolic-CH), 6.94 (d, J = 8.8, Hz, 2H Ar-H), 7.21 (d, J = 8.04, Hz, 2H Ar-H), 8.00 (brs, 2H, NH). 5.16.3.7 Synthesis of 5-(3,5 ditert-butyl-4-hydroxyphenyl)dipyrrolmethane (5h) The 3, 5-Di-tert-butyl-4-hydroxy-benzaldehyde (15.0 mmol, 3.5 gm) and pyrrole (30.0 mmol, 2.07 ml) were taken and rest of the procedure same as 5e

Physical state: white transparent crystal Rf : 0.40 (1:1 chloroform: pet. Ether, V/V) mp: 140 °C IR (KBr pellet, cm-1) 1H NMR (400MHz, CDCl3, 25˚C) δ = 1.41 (s, 18H, -C(CH3)3), 5.14 (s, 1H, phenolic-OH) 5.36 (s, 1H, -CH), 5.93 (d, 2H, β-pyrrole CH), 6.17 (m, 2H, β-pyrrole CH), 7.67 (m, 2H, α-pyrrole CH), 7.02 (s, 2H, Ar-H) and 7.87 (br s, 2H, NH)

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13C NMR (100MHz, CDCl3, 25˚C) δ: 30.28 (CH3), 34.30 (Cq), 43.86 (meso-C), 106.96, 108.23 (β-pyrrolic-C), 116.89, 124.96 (α-pyrrolic-C), 132.31, 133.27 (aryl-c), 135.83, 152.60 (aryl Cq). 5.16.3.8 Synthesis of 5-(3,5-di-methoxy-4-hydroxyphenyl)dipyrromethane (5i) The 3,5-di-methoxy-4-hydroxybenzaldehyde (15.0 mmol, 2.7 gm) and pyrrole (30.0 mmol, 2.07 ml) were taken and rest of the procedure same as 5e

Physical state: white crystals Rf : 0.40 (8:2 CHCl3: CH3OH, v/v) mp: 148-150 °C 1H NMR (400MHz, CDCl3, 25˚C) δ = 3.78 (s, 6H, -OCH3), 5.36 (s, 1H, phenolic-OH), 5.43 (s, 1H, -CH), 5.93 (d, 2H, β-pyrrole CH), 6.16 (m, 2H, β-pyrrole CH), 6.44 (s, 2H, phenyl), 6.68 (m, 2H, α-pyrrole CH), 7.98 (br s, 2H, NH) 13C NMR (100MHz, CDCl3, 25˚C) δ = 43.93 (meso-C), 56.17 (OCH3), 105.10, 107.03(β-pyrrolic-C), 108.28, 117.11(α-pyrrolic-C), 132.51, 133.10 (aryl-c), 133.47, 146.00 (aryl Cq). 5.16.3.9 Synthesis of 5-pentafluorophenyldipyrromethane (5j) The pentafluorobenzaldehyde (15.0 mmol, 2.9 gm) and pyrrole (30.0 mmol, 2.07 ml) were taken and rest of the procedure same as 5e

Physical state: Gray solid Rf : 0.46 (chloroform) mp: 130 °C (lit mp 131-132 °C). IR (KBr pellet, cm-1): 3343, 2956, 1460, 1255, 1117, 853, 731, 727 1H NMR (400MHz, CDCl3, 25˚C) δ = 5.87 (s, 1H, CH), 6.00 (s, 2H, β-pyrrolic, CH) 6.13-6.16 (m, 2 H, β-pyrrolic, CH), 6.70 (s, 2 H, α-pyrrolic, CH), 8.14 (br s, 2H, NH). 5.16.3.10 Synthesis of 5-(2,4,6-trimethylphenyl)dipyrromethane (5k) The mesitaldehyde (15.0 mmol, 2.2 gm) and pyrrole (30.0 mmol, 2.07 ml) were taken and rest of the procedure same as 5e

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Physical state: brown solid. Rf : 0.69 (1:1 chloroform: pet. Ether, V/V) mp: 170 °C (lit mp 170-17149 °C). IR (KBr pellet, cm-1): 3343, 2956, 1460, 1255, 1117, 853, 731, 727 1H NMR (400MHz, CDCl3, 25˚C) δ = 2.05 (s, 6 H, CH3), 2.27 (s, 3H, CH3), 5.91 (s, 1H, CH), 6.00 (s, 2H, β-pyrrolic, CH) 6.15-6.18 (m, 2 H, β-pyrrolic, CH), 6.65 (s, 2 H, α-pyrrolic, CH), 6.86 (s, 2H, Ar-H), 7.93 (br s, 2H, NH). 5.16.4 Synthesis of 26-π Hexaphyrin(1.1.1.1.1.1) (7a) The equimolar amount of 5-pentafluorophenyldipyrromethane (312 mg, 1 mmol) and pentafluorobenzaldehyde (195 µl, 1 mmol) were dissolved in dichloromethane methane sulfonic acid was added into the reaction mixture at ° C. After completion of reaction DDQ was added and reaction mixture was filtered through silica gel column eluting with chloroform gave the mixture of expanded porphyrins which were further purified by column chromatography to gave hexaphyrin as a second band as purple solid in modrate yield.

Physical state: purple solid. Rf : 0.39 (chloroform) mp: >250 UV-Vis [λmax CDCl3, (ε× 10-4, cm-1, M-1)]: 566 (21), 709 (1.7) nm. 1H NMR (400MHz, CDCl3, 25˚C) δ = -1.96 (brs, 2H, NH) -2.44 (s, 4H, β-pyrrolic, CH) 9.06 (d, J = 4.24 Hz, 4H, β-pyrrolic, CH), 9.42 (d, J = 4.24 Hz, 4H, β-pyrrolic, CH). 5.16.5 Synthesis of core modified sapphyrin The 2,5-bis[1-(4-tert-butyl-phenyl)-1-pyrrolomethyl]thiophene (103 mg, 0.204 mmol), 2,9-bis[1-(4-tert-butyl-phenyl)-hydroxymethyl]bisthiophene (100 mg, 0.204 mmol) were dissolved in 10 ml of dry dichloromethane and catalytic amount of acidic ionic was added into the reaction mixture at room temperature followed by DDQ oxidation

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gave the mixture of core modified expanded porphyrins which were purified by column chromatography over basic alumina.

Physical state: green solid Rf : 0.49 (chloroform) 1H NMR (400MHz, CDCl3, 25˚C) δ = -0.75 (s, 2H, β-thiophene-H), 1.59 (s, 36H, (C(CH3)3), 7.73 (d, J = 8.08 Hz, 8H, Aryl-H), 8.11 (d, J = 8.08 Hz, 8H, Aryl-H), 8.29 (d, J = 3.00 Hz, 2H, β-pyrrolic, CH) 8.41 (d, J = 3.00 Hz, 2H, β-pyrrolic, CH)), 8.88 (d, J= 2.92 Hz, 2 H, β-thiophene-H), 9.98 (d, J= 2.92 Hz, 2 H, β-thiophene-H). 5.16.6 Synthesis of 30π and 40π Expanded Porphyrinoids (11) A solution of pentafluoro benzaldehyde (1.2 ml, 10 mmol) and furan (0.73 ml, 10 mmol) in 100 ml of dry dichloromethane was placed in 250 ml flask under nitrogen. BF3.OEt2 (1.3 ml, 10 mmol) was added under dark, and the resulting solution was stirred for 1h. After adding FeCl3 (8.10 g, 50 mmol), solution was opened to air and stirred for two more hours. The reaction mixture was washed with water and passed through a short alumina column. This mixture was separated by silica gel column chromatography by using CH2Cl2/n-hexane as eluant. Two different colored fractions light blue (first) and pink color (last) fractions were obtained. Repeated purification of pink fraction by silica gel column chromatography, with 5% CH2Cl2 in n-hexane as eluant, yielded two different fractions, cyclo-hexa furans (0.045 g, 2%) and cyclo-octafurans (0.020 g, 1%) respectively.

Physical state: purple solid Rf: 0.67 (1: 1, CHCl3/ pet. Ether, v/v) Yield: 20 mg 2 % (w.r.t pentafluorobenzaldehyde) m.p.: > 300 oC 1H NMR (400MHz, CDCl3, 25˚C) δ = 2.52 (s, 6H, C-H), 7.91 (s, 6H, C-H) UV-Vis (λmax CHCl3) : 537, 645 nm ESI-MS: calculated 1470 (C66H12F30O6) ; observed (M+1) 1471 Synthesis of cyclo-octafuran (12) Physical state: purple solid.

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Rf: 0.60 (1: 1, CHCl3/ pet. Ether, v/v) Yield: 10 mg 1 % (w.r.t pentafluorobenzaldehyde) m.p.: > 300 oC 1H NMR (400MHz, CDCl3, 25˚C) δ = 5.80 (s, 8H, C-H), 9.06 (s, 8H, C-H) UV-Vis (λmax CHCl3) : 499, 536 nm. ESI-MS: calculated 1961 (C88H16F40O8) ; observed (M+1) 1962 5.16.7 Synthesis of 1,9-bisformyl-5,5-dipropyldipyrromethane (13) 5.16.7.1 Synthesis of 1,9-diformyl-5-ethyl-5-methyl-dipyrromethane (13b) In a 250 mL round-bottom flask, of 5-ethyl-5-methyldipyrromethane (5.00 g 26.5 mmol) was dissolved in 100 mL of DMF and cooled to 0°C. Next, 2.0 equiv of POCl3 (5.0 mL, 53.6 mmol) was added. After stirring for 4 h, the solution was made basic with concentrated aqueous NaOH (the effective solution pH = 11) and heated to reflux and held there for 2 h. Finally, the reaction mixture was quenched with water, extracted with ethyl acetate, and dried over anhydrous Na2SO4. Purification via column chromatography on silica gel (eluent: dichloromethane: ethyl acetate, 2:1) gave 5 in 77% isolated yield

Physical state: brown solid Yield: 4.81 gm (77 % w.r.t. 5-ethyl-5-methyldipyrromethane) Rf : 0.38 (CHCl3) IR (KBr pellet, cm-1): 3198, 2926, 1630, 1482, 1409, 1344, 1293, 1248, 1212, 1045, 999, 796, 773. 1H NMR (400MHz, CDCl3, 25˚C) δ = 0.76 (t, 3H, CH3), 1.62 (s, 3H, CH3), 2.10 (q, 2H, CH2), 6.20 (m, 2H, β-pyrrolic-CH), 6.82 (m, 2H, β-pyrrolic-CH), 9.16 (s, 2H, -CHO), 10.66 (brs, 2H, -NH) 13C NMR (100MHz, CDCl3, 25˚C) δ = 8.77 (CH3), 24.77 (CH3), 32.98 (CH2), 40.53 (meso-C), 109.34, 122.40 (β-pyrrolic-C), 132.40, 147.14 (α-pyrrolic-C), 179.09 (CHO). 5.16.7.2 Synthesis of 1-formyl 5,5-dimethyldipyrromethane (14) 1-Formyl-5,5-dimethyldipyrromethane: To a stirred solution of 5,5-dimethyldipyrromethane 1a (1.15 g, 5 mmol) in 10 mL of dry DMF cooled with ice-salt

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bath was added dropwise a solution of POCl3 (0.75 g, 5.4 mmol) in 2 mL of DMF under Ar. The mixture was stirred for 30 min at 0°C, then allowed to warm to room temperature for 1.5 h. The solution was then diluted with Et2O (50 mL) and extracted with water (3×15 mL), washed with Et2O (10 mL), adjusted to pH 8 with Na2CO3 solution, left overnight, cooled and the yellow precipitate was filtered off. The crude product was purified by column chromatography on neutral alumina with chloroform as the eluent followed by filtration through a pad of silica gel washed with chloroform. Treating with pentane after an evaporation of most of the solvent gave 0.75 g (58%) of title compound as cream-white crystals.

Physical state: cream-white crystals. Yield: 0.75 gm, 58 % (w.r.t 5,5-di-methyldipyrromethane) Rf : 0.35 ( CHCl3) IR (KBr pellet, cm-1): 3320, 3284, 2970, 2925, 1617, 1244, 1218, 1051, 773. 1H NMR (400MHz, CDCl3, 25˚C) δ = 1.67 (s, 6H, CH3), 6.07 (m, 3H, β-pyrrolic-H), 6.66 (m, 1H, β-pyrrolic-H), 6.87 (m, 1H, α-pyrrolic-H), 8.19 (brs, 1H, NH), 9.27 (brs, 1H, NH), 9.33 (s, 1H, CHO). 13C NMR (100MHz, CDCl3, 25˚C) δ = 28.65 (CH3), 35.74 (meso-C), 104.62, 107.65, 108.10, 117.70 (β-pyrrolic-C), 122.32, 131.96, 136.96, 149.12 (α-pyrrolic-C), 178.61 (CHO). 5.16.8 Synthesis of task specific basic ionic liquid 5.16.8.1 Butyl(2-hydroxyethyl)dimethylammonium hydroxide [bhyeda][OH-] (17) To a solution of [bhyeda][Br-] (9g, 40 mmol) (4) in dry methylene chloride (20 ml), powdered potassium hydroxide (2.3g, 40mmol) was added and the reaction mixture was stirred vigorously at room temperature for 24 h. The precipitated KBr was filtered off, and the filtrate was evaporated to leave the crude [bhyeda][OH-] as a viscous liquid that was washed with diethyl ether (3×20 ml) and dried at 90°C for 10 h to prepare the pure colorless ionic liquid for use.

Yield: 96% (6.23g) IR (neat, ν/ cm-1): 3435, 3247, 1486, 1047, 1027, 991, 959, 918. 1H NMR (400 MHz, D2O, δ): 4.1 (m, 2H, CH2OH), 3.4-3.5 (m, 4H, NCH2), 3.2 (s, 6H, NCH3), 1.76 (m, 2H, NCH2CH2), 1.34 (m, 2H, CH2), 1.1 (t, 3H, CH3).

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5.16.8.2 2-Hydroxyethyldimethylammonium acetate [hyeda][CH3COO-] (18) Distilled 2-dimethylaminoethanol (4.43g, 0.0498 mol) was placed in a 100 ml round bottom flask equiped with a dropping funnel. The flask was putted in an ice bath. Under vigorous stirring with a magnetic stirring bar acetic acid (0.0498 mol) was added dropwise (at 0°C) in about 45 minute. At room temperature stirring was continued for 24h to obtain a viscous clear liquid. The oily-viscous liquid was washed with diethyl ether (3×30mL) and dried under vacuum for 48h at 80°C to obtain a colorless viscous ionic liquid.

Yield: 96 % (7.13g) IR (neat, ν/ cm-1): 3392, 2738, 1641, 1568, 1409, 1342, 1173, 1081, 1016, 924, 882 1H NMR (400 MHz, D2O, δ): 3.70 (t, 3H), 3.15 (brs, 1H), 3.09 (t, 2H), 2.73 (s, 6H), 1.73 (s, 3H). 5.16.8.3 2-Hydroxyethylammonium acetate [hyea][CH3COO-] (19) Distilled 2-aminoethanol (20.24g, 0.33 mol) was placed in a 250 ml round bottom flask equipped with a dropping funnel. The flask was mounted in an ice bath. Under vigorous stirring with a magnetic stirring bar acetic acid (0.33 mol) was added dropwise (at 0°C) to the flask in about 30 minute. At room temperature stirring was continued for 24h to obtain a viscous clear liquid. The oily-viscous liquid was washed with diethyl ether (3×30mL) and dried under vacuum for 24h at 80°C to obtain a colorless viscous ionic liquid.

Yield: 92% (36.92g) IR (neat, ν/ cm-1): 3392, 1640, 1557, 1410, 1343, 1071, 1018, 925, 840 1H NMR (400 MHz, D2O, δ): 1.71 (s, 3H, CH3), 2.93 (t, 2H, CH2), 3.61 (t, 2H, CH2), 5.26 (brs, 3H). 5.16.8.4 1-Butyl-3-methylimidazolium hydroxide [bmim][OH-] (20) To a solution of [bmim][Br] (2g, 0.69 mmol) in dry methylene chloride (20 ml), powdered potassium hydroxide (0.69 mmol) was added and the reaction mixture was stirred vigorously at room temperature for 24 h. The precipitated potassium bromide

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was filtered off, and the filtrate was evaporated to leave the crude [bmim][OH-] as a viscous liquid. It was washed with diethyl ether (3×30 ml) and dried at 90°C for 10 h to afford the pure colorless ionic liquid. 5.16.9 Synthesis of 1,9-bis-(2-methylene-1,3-dimethylpyrimidine-2,4,6-trione)-5-

ethyl-5-methyl-dipyrromethane (21a) The 1,9-bisformyl 5-ethyl-5-methyldipyrromethane (122 mg, 0.5 mmol) and active methylene compound 1,3-dimethylpyrimidine-2,4,6-trione (156 mg, 1.00 mmol) were stirred in [bhyeda][OH] ionic liquid (5 mL) at 60°C temperature for half an hour. After completion of the reaction as indicated by the TLC, the mixture was poured in cold water and solid was filtered off. The crude solid was washed with several portion of water and dried under reduced pressure to afford the conjugated coloured solid compound, which was further purified by column chromatography using chloroform as eluting solvent. The rest of the viscous ionic liquid was further washed with Et2O and dried under reduced pressure to retain its activity in subsequent runs.

Physical state: brown solid Rf : 0.47 ( CHCl3) mp: 173 °C IR (KBr pellet, cm-1): 3423, 2927, 1654, 1522, 1310, 1246, 1050. 1H NMR (400MHz, CDCl3, 25˚C) δ = 0.91 (t, 3H, CH3), 1.85 (s, 3H, CH3), 2.23 (q, 2H, CH2), 3.35 ((s, 3H, NCH3),) 6.42 (m, 2H, β-Pyrrolic-CH), 7.08 (m, 2H, β-Pyrrolic-CH), 8.22 (s, -CHO), 13.56 (s, -NH) 13C NMR (100MHz, CDCl3, 25˚C) δ = 8.98 (CH3), 22.80 (CH3), 28.79 (CH2), 33.34 (meso-C), 41.59 (N-CH3), 104.73, 113.14 (β-pyrrolic-C), 129.18 (Cq) 130.81, 142.12 (α-pyrrolic-C), 150.65 (CH-C), 163.33, 163.75 (C=O, -C).

5.16.9.1 Synthesis of 1,9-bis(2’-methylene-indane-1,3-dione)-5-ethyl-5-methyl-dipyrromethane (21b)

Physical state: brown solid Rf: 0.49 (CHCl3) mp: 220 °C

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IR (KBr pellet, cm-1): 3424, 2927, 1654, 1545, 1271 1201, 1053, 1028 cm-1. 1H NMR (400MHz, CDCl3, 25˚C) δ = 0.97 (t, 3H, CH3), 1.96 (s, 3H, CH3), 2.33 (q, 2H, CH2), 6.43 (m, 2H, β-Pyrrolic-CH), 7.08 (m, 2H, β-Pyrrolic-CH), 7.61 (s, 2H, -CH), 7.63 (m, 4H, Ar-H), 7.81 (m, 4H, Ar-H)13.38 (s, -NH). 5.16.9.2 Synthesis of 1,9-bis(2’-methylene-1,3-diphenyl-2-thioxopyrimidine-4,6-

dione)-5-ethyl-5-methyl-dipyrromethane, (21c)

Physical state: brown solid Rf : 0.41 ( CHCl3) mp: < 250 °C IR (KBr pellet, cm-1): 3433, 2922, 1686, 1648, 1534, 1309, 1332, 1247, 1196, 1047, 991, 690, 547. 1H NMR (400MHz, CDCl3, 25˚C) δ = 0.81 (t, 3H, CH3), 1.26 (s, 3H, CH3), 2.04 (q, 2H, CH2), 6.37 (d, J = 4.4 Hz 2H, β-Pyrrolic-CH) 13C NMR (100MHz, CDCl3, 25˚C) δ = 8.87, 22.58, 29.65, 41.90, 105.60, 114.60, 128.82, 129.39, 129.96, 132.21, 139.77, 140.07, 142.97, 152.29, 162.27, 180.21. 5.16.9.3 Synthesis of 5,5-dimethyldipyrromethane-(2’-methylene-1,3-

dimethylpyrimidine-2,4,6-trione) (22a) 5,5-dimethyldipyrromethane-(2’-methylene-indane-1,3-dione (22b)

Physical state: brown solid Rf : 0.53 ( CHCl3) mp: 164 °C IR (KBr pellet, cm-1): 3294, 2923, 2854, 1654, 1497, 1345, 1307, 1215, 1046, 686. 1H NMR (400MHz, CDCl3, 25˚C) δ = 1.71 (s, 6H, CH3), 3.25 (s, 6H, -NCH3), 6.09 (m, 2H, β-pyrrolic-H), 6.26 (m, 1H, β-pyrrolic-H), 6.68 (m, 1H, β-pyrrolic-H), 6.97 (m, 1H, α-pyrrolic-H), 8.06 (s, 1H, CHO), 8.26 (brs, 1H, -NH), 13.27 (brs, 1H, -NH). 13C NMR (100MHz, CDCl3, 25˚C) δ = 28.08 (CH3), 29.67 (-NCH3), 36.45 (-meso-C), 103.58, 104.77, 108.19, 112.78 (β-pyrrolic-C), 117.76, 128.68, 131.51, 136.34 (α-pyrrolic-C), 141.57 (oliphinic-C), 151.66 (Cq), 155.45, 163.59 (C=O).

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5.16.9.4 Synthesis of 5,5-dimethyldipyrromethane-(2’-methylene-indane-1,3-dione) (22b)

Physical state: brown solid Rf : 0.56 ( CHCl3) mp: 207 °C IR (KBr pellet, cm-1): 3267, 2929, 1654, 1563, 1332, 1315, 1274, 1203, 1030 cm-1. 1H NMR (400MHz, CDCl3, 25˚C) δ = 1.81 (s, 6H, CH3), 6.17(m, 2H, β-pyrrolic), 6.26 (m, 1H, β-pyrrolic), 6.70 (m, 1H, β-pyrrolic), 6.94 (m, 1H, α-pyrrolic), 7.56 (s, 1H, -CH), 7.67 (m, 2H, Ar-H), 7.82 (m, 2H, Ar-H), 8.05 (s, 1H, -NH), 13.20 (s, 1H, -NH).

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