Upload
vandan
View
223
Download
0
Embed Size (px)
Citation preview
Chapter I
12
NAFION AS A CATALYST IN ORGANIC SYNTHESIS
The Nafion catalyst, a perfluroalkanesulfonic acid resin was developed by
DuPont chemists in early 1960 during work with General Electric on a fuel cell.1 The
IUPAC nomenclature of Nafion is tetrafluoroethylene-perfluoro-3,6-dioxa-4-methyl-
7-octensulfonic acid and the chemical formula is shown in Figure 1.
CF2
F2C
CF
F2C
OF2C
CF
CF3
OCF2
F2C
SO
OOH
n
m
Figure 1
Where is the value of m could be as low as 1 and the value of n ranges
between 6 to 13.2 It has hydrophobic (-CF2-CF2-) and hydrophilic (-SO3H) regions in
its structure and its super acidity due to the electron withdrawing effect of the
perfluoroalkyl backbone to which the sulfonic acid group is attached. The estimated
Hammett (H0) value for Nafion-H is comparable to that of 96-100% sulfuric acid
(H0 = -12.0).3
Nafion was first synthesized by the copolymerization of tetrafluoroethylene
(TFE) i.e. monomer in Teflon and the derivatives of a perfluoro (alkyl vinyl ether)
with sulfonic acid fluoride. The resulting product is an -SO2F- containing
thermoplastic that is extracted into films. Hot aqueous NaOH converted these sulfonyl
fluoride (-SO2F-) groups into sulfonate groups (-SO3-Na+). This form of Nafion is
referred to as a neutral or salt form, is finally converted to the acid form containing
the sulfonic acid (-SO3H) groups.
Chapter I
13
Nafion, the acidic form of the polymeric fluorinated sulfonic acid has been
widely investigated as an acidic catalyst for organic reactions.4 Nafion containing
substantial amount of water has been shown to be composed principally a source of
RfSO3-.H3O+ ion pairs and is potentially a source of H+aq. However, in its catalytic
chemistry, the material behaves as a much stronger acid than H+aq. The composition
of the materials explains its catalytic behavior.
Nafion is a heterogeneous recyclable Bronsted solid acid catalyst, acts as
water tolerant ion exchange resin. The swelling properties of the dried Nafion in
different solvents (i.e. methanol, water and trigyceride) were examined. Swelling in
water was investigated because it may be present in lower-quality biodiesel feed-
stocks. The kinetics of transesterification of vegetable oils, a highly refined olive oil
(acid value = 0.04) is also used, as a solvent for comparison. The catalyst dimensions
(obtained with a vernier caliper) and weights were measured for several Nafion
cylindrical-shaped pellets before and after soaking in the pure solvent at 60 °C
(typical transesterification reaction temperature) until equilibrium were reached.
Irreversible swelling after cooling has been proved to be a good assumption for this
type of system.5 The volume increase was measured and also estimated using the
relationship suggested6 to consider that the Nafion and the solvent volume are
additive. The resin was treated in methanol resulted in the high degree of swelling as a
result of physicochemical changes. Water showed a moderate capability for swelling
the resin, which is advantageous from the standpoint of greater acid site accessibility.
However, water may also lower the acid strength of the active sites7 or cause
deactivation via hydrolysis, as has been suggested for related sulfonic acid catalytic
materials.8 It has been reported that the mixture of short-chain alcohols and water
cause a greater degree of swelling than either the short chain alcohol or alone.
Chapter I
14
THF/water mixture provides the great degree of swelling of the Nafion resin (as
communicated by DuPont). Both short chain (triacetin) and long chain (olive oil)
triglycerides showed essentially no swelling capability for the perfluorinated resin,
which is analogous to the swelling characteristics obtained with free fatty acids such
as oleic acid.9 A change in color from transparent to dark amber was observed when
Nafion was soaked in either short-chain or long-chain triglycerides, indicating the
presence of possible side reactions (formation of carbonaceous deposits).
Nafion is unaffected by strong bases, strong oxidizing and reducing acids,
chlorine, oxygen, hydrogen, and hydrogen peroxide at temperature up to 125 °C.10 It
is thermally stable to about 170 °C in the acid form and stable to higher temperature
200-235 °C on replacement of protons by metal counter-ions.11
Nafion is a recyclable Bronsted acid catalyst and hence is able to catalyze a
variety of organic reactions such as transalkylation, ether synthesis, esterification, the
condensation of ketones, Pinacol-Pinacolone and Fries rearrangements.
The perfluorinated resin sulfonic acid (Nafion) is a recyclable heterogeneous
Bronsted acid catalyst which facilitates the various organic synthesis. Due to this
reason, it has received more attention in the area of organic synthesis.
Friedel-Crafts alkylation of benzene (1) with substituted alkenes (2) was
catalyzed by Nafion-H at 125-210 °C to yield the substituted benzene (3)
(Scheme 1).12
HC CH2R Nafion-H125-210 oC+
CHCH3
R
R = H, CH3
(3)(2)(1)
Scheme 1
Chapter I
15
Subsequently, Olah et al. has reported the use of Nafion-H in the Friedel-
Crafts acylation of aroyl chlorides (4) with toluene (5) to give substituted
methylbenzophenones (6) (Scheme 2).13
Nafion-H
R = H, 4-CH3, 2-F, 3-F, 4-F, 3-Cl(4) (5) (6)
ClC
ORCH3 C
O
CH3
R+
Scheme 2
The synthesis of mesitylene (8) and bromotoluene (9) was carried out by the
nucleophilic reaction of bromomesitylene (7) with toluene (5) in the presence of
Nafion-H catalyst under heating condition (Scheme 3).14
BrCH3H3C
CH3 CH3
BrCH3
Nafion-H,+ +
(7) (5) (8) (9)
CH3H3C
CH3
Δ
Scheme 3
Christian et al. has described the formation of pyrylium salts (12) from tertiary
and secondary alcohols (10) with carboxylic acid anhydrides (11) in the presence of
perfluorinated resinsulphonic acid Nafion-H (Scheme 4).15
OC
O
R1CO
R1R OH +
N
R
R1R1
Nafion-HCCl4, NH4OH
(10) (11) (12)R = t-Butyl alcohol, 2-Methylbutan-2-ol, 2-Methylpentan-2-ol, 3-Methylpentan-3-olR1 = Me, Et
Scheme 4
Chapter I
16
The 1,1-diacetates (15) were generally prepared by the equivalent amount of
aldehydes (13) and freshly distilled acetic anhydride (14) using catalytic amount of
Nafion-H at ambient temperature (Scheme 5).16
+ OC
O
CO
O
R
H
CH3
CH3
Nafion-H
(13) (14) (15)
CO
C
C
O
CH3
CH3
O
R H
O
R = Ph, p-O2NC6H4, p-ClC6H4, p-FC6H4, CH3, c-C6H11, Cl3C, C4H3O, o-ClC6H4, PhCH=CH-
Scheme 5
Fries rearrangement of phenol esters (16) to hydroxyphenyl ketones (17) was
carried out in the presence of Nafion-H (Scheme 6).17
Nafion-H
(16) (17)R = H, 4-CH3, 3-Cl; R1 = H, 4-CH3; X = OH, 2-OH
OC
O
C
O R1R R1 R
Scheme 6
The reductive cleavage of acetals (18) to the corresponding ethers (20) and
triethylsilane alkylethers (21) were carried out under Nafion-H catalysis with
triethylsilane (19) in refluxing dichloromethane solution (Scheme 7).18
CR1
R2 OR3
OR3Nafion-H CHO
R1
R2R3 (Et)3SiO R3
(20) (21)(18)
CH2Cl2,(Et)3Si H
(19)
+ +
R1 = H, Ph, CH3(CH2)8; R2 = H, CH3; R3 = CH3, C2H5
R1 = R2 =
Δ
,
Scheme 7
Chapter I
17
The Ritter reaction of alcohols (10) with nitriles (22) was described by Olah et
al. to yield the corresponding amides (23) using recyclable Nafion-H catalyst
(Scheme 8).19
R1 OH R1 HN RC
O
R C N Nafion-H,+
(10) (22) (23)
R = PhCH2, 2,4-Dimethyl-benzyl,1-Adamantane, 2-Adamantane, 2-Norbornane, exo-2-Phenyl-2-norbornaneR1 = CH3, Ph
Δ
Scheme 8
Nafion-H was reported an effective acid resin catalyst for the intramolecular
aromatic substitution of N-aryldiazoacetamides (24) to form the corresponding 2(3H)-
indolinones (25) in refluxing chloroform (Scheme 9).20
N
R1 N2
ZO
Nafion- H
(24)
R
N
R1
O
Z(25)
R = H, 2,3-(CH3)2, m-CH3, 3,4-CH2(O)2, α-NaphthylR1 = H, Et, Ben; Z = H, CH3CO
R
Scheme 9
The condensation of acetophenones (26) to 1,3,5-triarylbenzenes (27) was
catalyzed by Nafion-H under relatively mild reaction conditions at 145-150 °C
(Scheme 10).21
Chapter I
18
R1
R2
R1
R2
R2
R1
CH3O
R1
R2
Nafion-H145-150 oC
(26) (27)
R1 = H, CH3, CH3CH2, t-Bu, OCH3, Br, Cl, NO2; R2 = H, Br, OCH3
Scheme 10
Nafion-H was found to be an excellent acid catalyst for the direct conversion
of acetals (18) to thioacetals (28) with 1,2-ethanedithiol in methylene chloride
solution (Scheme 11).22
CR1
R2
OR3
OR3
HSCH2CH2SHNafion-H
CH2Cl2, reflux
CR1
R2
S
S
(18) (28)
R1 = Ph, CH3CH2CH2, CH3(CH2)5, (CH2)2, (CH2)5, (CH2)6 R2 = H, CH3, Ph, CH3CH2CH2, CH3(CH2)5, (CH2)2, (CH2)5, (CH2)6 R3 = MeO, EtO, ; R1 = R2 =
Scheme 11
Friedel-crafts reaction of substituted calix[4]arenes (29) with diphenyl ether in
the presence of Nafion-H resulted in the formation of [9,9]spirobixanthene (30)
(Scheme 12).23
Chapter I
19
OH HOOHOHR R
R
R
Nafion-H(Ph)2O C
O
O
(29) (30)R = t-Bu, H
Scheme 12
Kobayashi et al. has described Sc-Nafion catalyzed allylation reaction of
carbonyl compounds (31) with tetraallyltin (32) to afford the desired homoallylic
alcohols (33) in high yields at room temperature (Scheme 13).24
Sn
4
+ Nafion-ScCH3CN, rt R
OH
(33)(31)R = Ph, PhCH2, Ph(CH2)2, 2-Pyridine, PhHC=CHR1 = H, CH3, COOMe; (31) = D-arabinose, D-ribose, D-glucose
(32)
R R1
O
R1
Scheme 13
Nafion-H was found to be an highly efficient solid acid catalyst for the
biomolecular conversion of alcohols (10) to ethers (34) in excellent yields (Scheme 14).25
2 R OH Nafion-H,O RR-H2O
(10) (34)R = CH3(CH2)4, CH3(CH2)5, CH3(CH2)6, CH3(CH2)7, CH3(CH2)8, CH3(CH2)9, 3-MeC4H9, 2-EtC6H12, 3,7-Me2C8H15, 3,5,5-Me3C6H10, c-C6H11, 1-MeC4H8, 1-EtC4H8, 1-MeC7H14,
Δ
Scheme 14
Chapter I
20
Mukaiyama aldol condensation was carried out between aromatic aldehydes
(35) and the Danishefsky diene (36) which undergo Diels-Alder cyclization to form
the 2,3-dihydro-γ-pyridones (38) through the formation of imine intermediate (37) in
the presence of Nafion-H (Scheme 15).26
Me3SiO
OMe
+
XH
Nafion-HOMe
XSiMe3O
RX
O
(36)(35) (37) (38)
R
X = O, NPh; R = H, 3-CH3, 2-NO2, C4H3O, 4-CH3, 4-OCH3, 4-Br, RC6H4 = 2-Furyl, 3-PyridylR
Scheme 15
Vankar et al. has reported that the catalytic amount of Nafion-H along with
NaI (1 equiv.), in methanol cleaved a variety of tert-butyldimethyl silyl ether
(TBDMS) (39) readily in to corresponding alcohols (10) in high yields
(Scheme 16).27
Nafion-H, NaIMethanol
(39) (10)R OTBDMS R OH
R = Alkyl, Aryl, Cyclic
Scheme 16
The deprotection of trimethylsilyl ethers (40) to their corresponding alcohols
(10) was carried out in the presence of Nafion-H and wet SiO2 in n-hexane at room
temperature (Scheme 17).28
Chapter I
21
R OTMSNafion-H,
n-Hexane, rt R OH(40) (10)
R = 4-CH3OC6H4CH2, 4-(CH3)2CHC6H4CH2, 4-(CH3)3CC6H4CH2, 2-ClC6H4CH2, 2,4-Cl2C6H3CH2, 2-BrC6H4CH2, 2-O2NC6H4CH2, 3-O2NC6H4CH2, 4-O2NC6H4CH2, n-C7H15, n-C8H17, PhHC=CHCH2,
wet SiO2
H2C
O
O
CH2
H2C
H2C
O CH2
H2C
CH2
CH3
H2C
,
,,
,
,,
,
Scheme 17
The one-pot three-component synthesis of 2,3-disubstituted 4-(3H)-
quinazolinones (44) from o-aminobenzoic acid (41), alkyl/aryl-trietoxymethanes (42)
and aromatic amines (43) was catalyzed by Nafion-H under solvent-free microwave
irradiation conditions (Scheme 18).29
OH
NH2O
NH2
R C
OEt
OEt
OEt R1+ + Nafion-HMW
N
N
OR1
R
(44)(41) (42) (43)
R = H, Me, Et, Ph; R1= 3-CF3, 4-CF3, 2,4-(NO2)2, 2-Cl-5-CF3
Scheme 18
The multicomponent reaction of cyclic β-diketones (45), urea (46) and
aldehydes (13) was reported for the synthesis of octahydroquinazolinone derivatives
(47 & 48) over Nafion-H with good yield and selectivity (Scheme 19).30
Chapter I
22
Nafion-HEthanol, refluxH2N NH2
O
(46)
+
O
OR
R
(13)
R = H, CH3R1 = C6H5, 4-H3CC6H4, 3-ClC6H4, 4-ClC6H4, 2-BrC6H4, 3-BrC6H4, 4-BrC6H4, 4-O2NC6H4, 4-CH3OC6H4, 4-FC6H4, 3-FC6H4, 2,4-Cl2C6H3, 3-Pyridine, 4-Pyridine
R1 H
O
O
NH
HN O
R1O
O O
R
R
R1
R
R
R
R
+
(45)
(48)
(47)
Scheme 19
Narsaiah et al. has developed a one-pot multicomponent condensation of aryl
aldehydes (13), enolisable ketones (49) and acetyl chloride (50) using Nafion-H
catalyst for the synthesis of β-acetamido ketones in acetonitrile (51) at room
temperature (Scheme 20).31
R1
O
CH3COCl Nafion-HCH3CN, rt
R R1
ONHAc
+ +
(13) (49) (50) (51)R= Ph, 4-FC6H4, 4-O2NC6H4, 2-O2NC6H4, 3-O2NC6H4, 4-MeOOCC6H4, 2-ClC6H4, 4-MeOC6H4, 4-ClC6H4, 4-H3CC6H4R1 = Ph, 4-ClC6H4, 4-H3CC6H4, 4-MeOC6H4, 4-O2NC6H4, 4-BrC6H4; R2 = H
R H
O R2
R2
Scheme 20
The hydroamination of vinylpyridines (52) with aliphatic and aromatic amines
(53) was developed for the synthesis of disubstituted-(2-pyridin-2-yl-ethyl)-amines
(54) using cation exchange resin Nafion-NR50 under milder reaction conditions
(Scheme 21).32
Chapter I
23
N
+ NH
R1
R2
Nafion-NR50Ethanol, reflux
NN
R1
R2
(52) (53) (54)R1= H, Aryl, Alkyl; R2 = Aryl, Alkyl
Scheme 21
A novel one-pot solvent-free synthesis of 1,3,4-oxadiazoles (57) was
reported by the condensation of acid hydrazides (55) and triethyl orthoalkanates
(56) using solid supported Nafion®NR50 under microwave irradiation
(Scheme 22).33
Nafion NR50
R1 = H, F, OMe, 2-Furyl, 2-Thienyl, 4-Pyridyl; R2 = H, Et, C6H5
N N
O R2
R1
NHNH2
O
R1O O
R2 O
(55) (56) (57)
+ MW
®
Scheme 22
The Ritter reaction of nitriles (58) and alcohols (59) was reported for solvent-
free synthesis of amides (60) catalyzed by Nafion®NR50 under microwave irradiation
(Scheme 23).34
Nafion NR50MW, 130 oC
CR1 N R2
OH
NH
R2
O
R1+
R1 = H, MeO, Cl; R2 = H, Me, MeO, Cl, Naphthyl, Adamantyl
(58) (59) (60)
®
Scheme 23
Chapter I
24
The one-pot synthesis of nitrones (62) via direct condensation/oxidation of
aldehydes (13) and primary amines (61) using Nafion immobilized MoOCl4 as
catalyst and solid urea-hydrogen peroxide (UHP) as oxidant was described under very
mild reaction conditions (Scheme 24).35
R1 H
O
+ H2N R2 Nafion-MoUHP, MeOH, rt N+ R2
O-
R1
(13) (61) (62)
R1 = Ph, 4-MeOC6H4, 4-O2NC6H4, 2-Furyl, CH3(CH2)2CH2 R2 = PhCH2, n-Bu, t-Bu
Scheme 24
Kidwai et al. has reported the synthesis of 2-aminothiazoles (65) from α-
bromoketones (63) with thiourea derivatives (64) using Nafion-H as a solid acid
catalyst coupled with aqueous PEG-400 system (Scheme 25).36
CH2Br
O
+ CH2N NHR1
S
PEG:water (60:40)N
SNHR1
(65)(63) (64)
R = H, p-Me, p-BrR1 = H, Ph, 2-Naphthyl, p-BrC6H4, p-MeOC6H4, p-MeC6H4, p-HOC6H4, p-O2NC6H4
Nafion-H, 50 oC
R
R
Scheme 25
Chapter I
25
PROPARGYLAMINES
Propargylamine or propargylic amines (66) are highly useful building blocks
in organic synthesis and the corresponding structural motif has been found in various
natural products and compounds of pharmaceutical relevance.37
NH
(66)
The classical methodologies for the preparation of propargylic amines have
usually exploited the relatively high acidity of terminal acetylenic C-H bond to form
alkynes-metal reagents by the reaction with strong base.
Propargylamines are versatile synthetic intermediates for organic synthesis,
especially for the synthesis of heterocyclic compounds such as oxazolidinones,
imidazoles and pyrroles etc.
4-Methylene-2-imidazolidinones (69) were obtained by the base catalyzed
cyclization of propargylic ureas (68), which were synthesized by the reaction of 3-
alkylamino-1-butyne (67) with isocyanate (Scheme 26).38
HNH
H3C
R1R2NCO NaOCH3
HN
H3C
R1NHR2
ON
N
O
R2
R1
H3C
CH2
(67) (68) (69)
R1 = c-C6H11, (CH3)3C-CH2-(CH3)2C; R2 = 4-ClC6H4, 2,5-Cl2C6H3
Scheme 26
Reaction of β-oxodithioesters (70) with propargylamine (71) afforded the
corresponding 2-(acylalkylidene)-5-(methylene)thiazolidines (72) (Scheme 27).39
Chapter I
26
R SMe
O S+ HC C CH2NH2
EtOHR S
O HN
(70) (71) (72)R = CH3, C6H5, 4-MeOC6H4
Δ
Scheme 27
Reaction of 1-(N-methyl-N-phenylaminomethyl) benzotriazole (73)
with alkynylalkylaluminates (74) gave corresponding propargylamines (75)
(Scheme 28).40
(73) (74) (75)
N
NN
NPh
R)2NaEt2Al(+R
N Ph
R = H, C6H5
Scheme 28
Copper(I)-catalyzed direct alkyne-imine addition reaction of N-
benzylideneanilines (77) with phenylacetylene (76) was carried out in the presence of
H2O resulted in the formation of propargylamines (78) (Scheme 29).41
R H2O or Toluene
R = Ph Ar' = C6H5, 4-MeC6H4, 4-ClC6H4, 4-BrC6H4Ar = C6H5, 4-MeC6H4, 4-EtC6H4, 4-ClC6H4, 4-BrC6H4
(76) (77) (78)
+H 10 mol% Cu(OTf)
Ar
NHAr'
Ph
N
Ar
Ar'
Scheme 29
Chapter I
27
Enantioselective, Copper(I)-catalyzed three-component reaction of alkynes
(76), aldehydes (13) and secondary amines (53) was reported to afford the
corresponding propargylamines (79) in toluene at room temperature by using CuBr (5
mol%) and (R)-quinap (R)-2 (5.5 mol%) (Scheme 30).42
R
R = C6H5, n-Bu, 4-BrC6H4, SiMe3, c-Hex; R1 = Ph, i-Bu, i-Pro, c-Hex, 1-Ethylpropayl, 4-MeOC6H4, 4-F3CC6H4, 2-H3CC6H4, 3-Furanyl, 3-Benzothiphenyl; R2 = R3 = Bn, Allyl
(76) (13) (53) (79)
NHR2
R3+H
R2 N
R3
RR1
R1 H
O
+(R)-quinap (R)-2
(5.5 mol%)
CuBr (5 mol%)Toluene, rt
Scheme 30
Substituted propargylamides (82) were obtained by the metal catalyzed
coupling of imines (80) with alkynes (76) and acid chlorides (81) (Scheme 31).43
R CH3CN, rt
R = C6H5, (CH3)3Si, CH2Cl, n-C4H9R1 = 4-H3CC6H4, 4-H3CSC6H4, 4-BrC6H4R2 = Bn, H2COOCCH3, C2H5; R3 = C6H5, CH3, i-Pr
+HCuI, i-Pr2NEt
O
R3 ClR1 H
NR2
+N
R1
R
R2
O
R3
(76) (80) (81) (82)
Scheme 31
Reaction of activated quinolines (83) with terminal acetylenes (76) in the
presence of copper iodide and i-Pr2NEt afforded the corresponding 2-alkynyl-1,2-
dihydroquinolines (84) (Scheme 32).44
Chapter I
28
R
R = C6H5, CH3(CH2)4CH2, CH2OH
HCuI
+
(76) (83) (84)
CH2Cl2, rti-Pr2NEt
N
OEtO
Cl-N
OEtOR
Scheme 32
Reaction of alkynes (76) to N-tert-butanesulfinimines (85) in the presence of a
base lithium hexamethyldisilazide (LiHMDS) provided the corresponding N-tert-
butylsulfinylpropargylamines (86) (Scheme 33).45
R n-Hexane
R = C6H5, (CH3)3Si, n-C4H9R1 = C6H5, 4-CH3OC6H4, n-Bu, t-Bu, i-Pr, trans-PhCH=CH
HLiHMDS
R1 H
NS
+HN
R1
R(76) (85) (86)
O
-78 oC to rt
S
O
Scheme 33
α-[4-(1-Substituted)-1,2,3-triazol-4-yl]benzylacetamides (88) were obtained
via microwave-assisted Cu(I)-catalyzed reaction of chiral propargylamines (87) with
phenyl azide or sodium azide (Scheme 34).46
NHR1
R
NHR1
N
NN
n1. Ac2O, Et3N, CH2Cl2, rt2. NaN3, C6H5CH2Cl
sodium ascorbate/(CuSO4),H2O/t-ButOH, MW
R = H, 4-F, 4-Br, 4-Cl; R1 = Ac, H; n = 0,1
(87) (88)
R
Scheme 34
Chapter I
29
Au-nanoparticles were catalyzed multicomponent A3-coupling reaction of
aldehydes (13), amines (53) and alkynes (76) to give the propargylamines (89) in
excellent yields at 70-80 oC under nitrogen atmosphere (Scheme 35).47
R
R = C6H5, 4-MeC6H4, 4-MeOC6H4, 3-ClC6H4, 4-BrC6H4, 2-Furfuryl, 2-Thiophenyl, 3-Pyridenyl R2R3NH = Piperidine, Morpholine, Pyrrolidine
(13) (53) (76) (89)
NH
R2
R3
+ H
R2
NR3
R
R1 H
O
+R1
10 mol% Au-np (18 2 nm)±THF 75-80 oC, N2, 1 atm
Scheme 35
Addition of lithium trifluoromethylacetylide (90), in situ prepared from
lithium diisopropylamide and 2-bromo-3,3,3-trifluoropropene to various N-tert-
butanesulfinyl imines (91) provided the corresponding trifluoromethylated propargyl
sulfinamides (92) (Scheme 36).48
Li
R1 = CH3 ; R2 = C2H5, C6H5, i-Pr, i-Bu
F3CMe3Al
(90) (91) (92)
Toulene+S
N R2
O R1NH
SO
R2
R1
CF3
Scheme 36
Propargylamines (94) were obtained by the reaction of phenylacetylene (93)
and aldehydes (13) with heterocyclic amines (53) using zinc titanate nanopowder in
aqueous medium at 100 oC (Scheme 37).49
Chapter I
30
R = Ph, 4-ClC6H4, 4-BrC6H4, 2-HOC6H4, 3,4-(MeO)2C6H3, 4-Me2NC6H4, 4-ClC6H4, CH3CH2CH2 R1R2NH = Piperidine, Pyrrolidine, Morpholine, Piperazine, N-Methylpiperazine
(93) (13) (53) (94)
NHR1
R2
+
H R1
NR2
R H
O
+Rwater (5 mL)
100 oC
Zinc titanatenanopowder
(5 mol%)
Scheme 37
NiCl2-catalyzed A3-coupling reaction of alkynes (76), aldehydes (13) and
amines (53) gave the corresponding propargylamines (89) in quantitative yields
(Scheme 38).50
R
R = Ph, CH3(CH2)5, 4-MeC6H4, (CH3)3Si R1 = H, C6H5, 4-O2NC6H4, 3-O2NC6H4, 4-FC6H4, 4-MeC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, Cyclohexyl, 2-ClC6H4, 3-ClC6H4, 2,4-Cl2C6H3, Me2CH, 2-Thiophene R2R3NH = Piperidine, Pyrrolidine, Morpholine, Piperazine, N-Methylpiperazine, N-Methylaniline, Aniline, Dibenzyl amine, N-Methylpiperazine, Ammonia, Benzylamine, Methyl amine, n-Butylamine, Ethyl-1-piperazinecarboxylate
(76) (13) (53) (89)
NHR2
R3
+H
R2
NR3
R
R1 H
O
+
R1Toluene, 100 oC
NiCl2
Scheme 38
Fe3O4 nanoparticle-supported copper(I) pybox-catalyzed enantioselective
direct-addition reactions of terminal alkynes (76) to imines (95) gave the
corresponding propargylamines derivatives (96) (Scheme 39).51
Chapter I
31
N
R1
R
HN
R2
R2H
Fe3O4 nanoparticle-supported copper(I)pybox catalyst
(10 mol%)CH2Cl2
R
R1
+
(95) (76) (96)
R = H, p-Br, p-Cl, p-CF3; R1 = H, p-Br; R2 = Ph, p-MeC6H4
Scheme 39
The synthesis of various propargylamines (97) was achieved by the simple
Barbier–Grignard-type reaction of phenylacetylene (93) with a variety of aldimines
(80) catalyzed by a bimetallic In–Cu system under aqueous condition (Scheme 40).52
NR1
R
HN
R1
R+
(93) (80) (97)
R = R1 = H, 4-ClC6H4, 4-MeC6H4, 4-MeOC6H4, 4-O2NC6H4, 4-MeC6H4SO2
In-CuH2O, 40 oC
Scheme 40
Gold nanoparticles impregnated on alumina catalyzed A3-coupling reaction of
aldehydes (13), amines (53) and alkynes (76) to give corresponding propargylamines
(89). The aldimine (98) formation was catalyzed by Montmorillonite K10 beforehand
(Scheme 41).53
R2NH
R1
R1
HR H
O
+N
R1
R
R1
NR1
R2R
R1
Au-np@Al2O3 80 oCMM K-10 25 oC
(76)
(13) (53) (98) (89)R = C6H5, C5H5N, C4H3O, C6H5CH2CH2, CH3(CH2)5R1R1NH = Piperidine, Morpholine, Pyrrolidine, Diethylamine, 2-(Methylamino)ethanolR2 = C6H5
Scheme 41
Chapter I
32
Pargyline derivatives (99) and (100) were prepared from 8-
(methylaminomethyl)quinoline and exhibited anti-monoamine oxidase activity.54
H2C NCH2C CH
Me(99)
N
N CH2C
(100)
Me CH
The propargylamine derivative (101) potentiated tryptamine convulsions of
rats similar to Pargyline had slight stimulating effect.55
H2C NMeCH2C CH(101)
A series of 10-propargyl-5,8-dideazafolic acid derivatives (102) were
synthesized and tested for inhibition of purified L1210 thymidylate synthase and for
inhibition of L1210 cell growth in vitro.56
(102)
HN
N
CH2N
R
O CH2C CH
R2
R1
R3
R = NH2; R1 = H, Cl, MeOR2 = H, Cl, Ac, F, CN, CONH2, SO2NMe2, NO2, COCF3, OCF3 R3 = H, MeO
A series of acetylenic imidazoles (103) related to oxotremorine were prepared
and evaluated as cholinergic agents with in vitro binding assays and in vivo
pharmacological tests in mice.57
Chapter I
33
NCH2C CCH2NN
O R
R1
R = H, MeR1 = H, Me
(103)
2-Alkynyl and 2-cycloalkynyl derivatives of adenosine-5'-N-ethyluronamide
(NECA) (104) were prepared as selective A2 adenosine receptor agonists with potent
inhibitory activity on platelet aggregation.58
N
N N
N
CRC
O
OH OH
EtHNOC
R = H, Hydroxyalkyl, 1-Hydroxycyclopentyl, Aminoalkyl, 1-Aminocyclohexyl, Alkenyl, (CH2)3CN, (CH2)3Cl
(104)
NH2
Cyclo-hexapeptide analogue (105) was synthesized starting from
propargylamine and found to possess anti-parallel β-sheet structure.59
CHN
Me
NH
C
HN
O
NH
Me
C
C
Me(105)
O
Chapter I
34
2-(2,6-Difluorophenyl)-4-phenylalkynyl oxazolines (106) were prepared as a
potent insect growth regulators.60
F
F
N
OR
R = Me3C, Me3CO, H, CF3, 4-CF3SO3C6H4, 4-BrC6H4, 4-FC6H4, Ph(106)
Compound (107) related to 2-azatidinone was synthesized as single
enantiomer and found to be potent cholesterol absorption inhibitors.61
(107)
N
O
HO
F
NH
HN
O
O O
OH
HO OH
OH
O
O
O
O
COOHHO
Chapter I
35
[(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate (108) was
synthesized as anti-apoptotic-neuroprotective agent and as a novel
cholinesterasemonoamine oxidase inhibitor.62
HNO
O
N
(108)
1,8-Naphthyridine-3-carboxamide derivatives (109) were synthesized as
anticancer and anti-inflammatory agent and tested for in vitro cytotoxicity against
eight cancer cell lines and a normal cell line with IC50 = 1.37 μM for HBL-100
(breast) cell line.63
N N
O
NH
O
O O
NH
OBu-tO
CH(109)
R
R = Cl, Me
1-alkyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline derivatives (110) were
synthesized from 2-phenylethylamine and showed cytotoxic effect on PC12 cells.64
N
R
R = Ph, Methyl, Ethyl, n-Propyl, n-Butyl, n-Pentyl, n-Hexyl cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, 3-Hydroxypropyl, 3-Acetoxypropyl
(110)
Rasagiline (N-propargyl-1-(R)-aminoindan) (111) was synthesized as potent
irreversible monoamine oxidase (MAO)-B inhibitor, anti-Parkinsonian drug and
Chapter I
36
effected as monotherapy or adjunct to L-Dopa for patients with early and late
Parkinson’s disease (PD).65
HN(111)
The length of synthesis is dependent upon the average molecular complexity
produced per operation, which depend in turn on the number of chemical bonds being
created. Therefore, devising reaction that achieves multi-bond formation in single
operation is becoming a major challenge in search of step economy synthesis.
Multicomponent Reactions (MCRs) found to be a straight forward route to generate
complexity with diversity in a single operation. MCRs processes66, in which three or
more reactants are combined in a single chemical process to produce product that
incorporate substantial portions of all the components, naturally comply with many of
stringent methods required for ideal organic synthesis.
MCRs, though fashionable these days, have in fact a long history. Indeed,
many important reactions such as the Strecker amino acid synthesis (1850)67, the
Hantsch dihydropyridine synthesis (1882)68, the Biginelli dihydropyrimidine (1891)69
and the Mannich reaction70 etc. are all multicomponent in nature. Inspite of the
significant contribution of MCRs to the state of the art of the modern organic
chemistry and their potential use in complex organic syntheses, little attention was
paid to the development MCRs. However, with the introduction of molecular biology
and high-throughput biological screening, the demand on the number and the quality
of compounds for drug delivery has increased enormously. By virtue of their inherent
convergence and high productivity, together with their exploratory and complexity-
Chapter I
37
generating power, MCRs became a rapidly evolving field of research and have
attracted the attention of both academic and industrial scientists.
Carbon-Carbon bond-forming reactions are arguably the most important
processes in chemistry, as they represent the key step in the building of more complex
molecules from simple precursors. In the past few years, organic chemists have
developed a plethora of reactions for carbon-carbon bond formation between saturated
sp3 C-atoms. However, until the discovery and development of metal-mediated cross-
coupling reactions, starting in 1970s, there was no simple, general direct methodology
known for carbon-carbon bond formation between unsaturated species such as aryl,
vinyl and alkynyl moieties. In other words, carbon-carbon bond formation between sp
and sp2 C-atom centers are often difficult and tedious. In the intervening 25 years, a
wide variety of cross-coupling methodologies have been developed and cross-
coupling reactions have emerged among the most powerful and useful synthetic tools
in chemistry.71
Chapter I
38
OBJECT OF THE PRESENT WORK
An increasing awareness of the environmental cost of traditional acid-
catalyzed chemical processes has created an opportunity for new solid acid-based
approaches to many important industrial reactions.72,73 The replacement of
conventional, toxic and polluting Bronsted and Lewis acid catalysts with eco-friendly
reusable solid acid heterogeneous catalysts like acidic zeolites, clays, sulfated zirconia
and ion exchange resins is an area of current interest.74-77 The use of solid acid
catalyst instead of liquid includes many advantages such as reduced equipment
corrosion, ease of product separation, recycling of the catalyst and environmentally
acceptability.
In recent years, resins containing perfluorosulphonic acid group such as
Nafion®NR5078 (copolymer of tetrafluroethylene and perfluoro-2-
(fluorosulfonylethoxy) propyl vinyl ether), which is strongly acidic in nature and
chemically as well as thermally stable has been found to be an excellent catalyst for a
variety of major organic reactions like alkylation, acylation, esterification,
etherification, dehydration and nitration.79,80
Multicomponent coupling reactions (MCRs) provide a powerful synthetic
strategy to access complicated structure from rather simple starting material via a one-
pot methodology, and in particular, exhibit high atom economy and selectivity.81 As
continuation, a very good example of such a process that has been studied widely in
recent years is three-component coupling of aldehydes, amines and alkynes (A3-
coupling) via C-H activation.82,83 The propargylamines that result from A3-coupling
reactions are versatile building blocks for organic synthesis. They are generally used
as precursors for the synthesis of N-containing heterocyclic compounds such as
pyrrolidines, oxazoles and pyrroles84 and also act as key intermediates85 for the
Chapter I
39
construction of biologically active compounds like isosteres, β-lactams, oxotremorine
substrates, conformationally restricted peptides and therapeutic drug molecules.86
Traditionally, propargylamines are synthesized by nucleophilic attack of lithium
acetylides or Grignard reagents to imines.87 In recent years, enormous progress has
been made in expanding the scope of the direct addition of alkynes to carbon-nitrogen
double bonds either from prepared imines or from aldehydes and amines in one-pot
procedure by several transition-metal catalysts via C-H activation of terminal alkynes.
These include Ag(I) salts88, Au(I)/Au(II) salts89, Au(III)-salen complexes90, Cu(I)
salts91, Hg2Cl292 and Cu/Ru93 bimetallic system under homogeneous conditions.
Recently, Au(III)94, Ag(I)95, in ionic liquids and Cu-supported hydroxyapatite96 were
used to catalyze A3-coupling reactions. Also, more sophisticated alternative energy
sources like microwave91 and ultrasonic97 radiation has been used in the presence of
Cu(I) salt.
Unfortunately, these reagents used in stoichiometric amounts are often lost at
the end of the reaction (non-recyclable) and required drastic reaction conditions. Most
of these reactions were carried out either in toxic solvents88 or in the presence of
expensive solvents.98 Thus, there has been an ongoing interest to develop solid acid
catalysts for C-H bond activation of terminal alkynes99 under mild reaction
conditions.
As a part of our ongoing program on the development of new synthetic
methods and the use of recyclable heterogeneous catalyst in organic synthesis100,101
herein, we wish to report for the first time a simple and highly efficient methodology
for the synthesis of propargylamines in excellent yields using Nafion®NR50 as
recyclable and heterogeneous solid acid catalysts.
Chapter I
40
RESULTS AND DISCUSSION
As a model reaction, we initially examined an efficient and environmentally
benign protocol for A3-coupling of benzaldehyde (112a) (1.0 mmol), piperidine
(113a) (1.2 mmol) and phenylacetylene (114) (1.5 mmol) in the presence of
Nafion®NR50 in acetonitrile at 70-80 oC under nitrogen atmosphere (Scheme 42). As
a result, the expected reaction proceeded clearly to produce the desired
propargylamine in 96% yield (115a).
The effect of catalyst loading was studied by carrying out the experiments
with different amounts of Nafion®NR50. Increasing the loading of catalyst up to 0.35
gm gave desired propargylamines in 96% yield. However, the increase in the
concentration of catalyst not only promotes the reaction but also results in an increase
of the yield with decrease in the time (Table 1).
In addition, it was found that at higher temperature Nafion®NR50 showed
good catalytic activity at 70-80 °C, 96% yield was obtained, however at room
temperature lower yields were obtained even after longer reaction times. Comparable
results were obtained when the reaction was carried out at 70-80 oC with 0.25 gm of
Nafion®NR50. Thus, to reduce the amount of catalyst, all optimization was carried
out at 70-80 oC with 0.25 gm of Nafion®NR50.
The nature of reaction media has an important role in A3-coupling reaction in
the presence of Nafion®NR50 (0.25 gm). Among the various solvents studied such as
acetonitrile, methanol, THF, DCM and dioxane, acetonitrile was found to be the most
efficient solvent of choice (Table 2, Entry 1) and no products were obtained when
the reaction was carried out in dichloromethane or dioxane.
Chapter I
41
A possible mechanism was proposed 88c,89b,91a,98 involving the activation of C-
H bond of the terminal alkyne by Nafion®NR50 catalyst (Scheme 43). The sulfur
acetylide intermediate thus generated will react with the iminium ion prepared in situ
from aldehyde and secondary amine to produce the corresponding propargylamines,
water and Nafion®NR50. The regenrated Nafion®NR50 participates further in the
reaction and completes the catalytic cycle.
For the practical application of the catalyst Nafion®NR50, the life-time of the
catalyst and its level of reusability are important factors. The catalyst showed
excellent recyclability and could be reused for three to four runs with only slight drop
in activity. After completion of fresh reaction the catalyst was recovered by forceps,
washed with dichloromethane, dried and new reaction was then performed under
similar reaction conditions (Table 3).
After completing the search of optimized conditions, we chose a variety of
structurally different aldehydes, and amines possessing a wide range of functional
group to understand the scope and generality of Nafion®NR50 promoted A3-
coupling reaction. A variety of aromatic aldehydes were coupled with secondary
amines and phenylacetylene and it was found that aryl aldehydes possessing an
electron withdrawing groups (Table 4, Entries 4-6) afforded better yields with
good reactivity and lesser reaction times than those with electron donating groups
(Table 4, Entries 2 and 3) bound to the benzene ring required longer reaction
times. Heterocyclic aldehyde (Table 4, Entry 7) also displayed high reactivity
with good yield.
Chapter I
42
+R-CHO +Nafion®NR50, CH3CN
70-80 oC, N2 atmR1R2NH
NR2
R1
R
(112) (113) (114) (115a-n)
(a) R = C6H5; R1R2NH = Piperidine, (b) R = 4-MeC6H4; R1R2NH = Piperidine(c) R = 4-MeOC6H4; R1R2NH = Piperidine(d) R = 4-BrC6H4; R1R2NH = Piperidine(e) R = 4-ClC6H4; R1R2NH = Piperidine(f) R = 4-NO2C6H4; R1R2NH = Piperidine(g) R = 2-Furfuryl; R1R2NH = Piperidine(h) R = Cyclohexyl; R1R2NH = Piperidine(i) R = C6H5; R1R2NH = Morpholine(j) R = 4-MeC6H4; R1R2NH = Morpholine(k) R = 4-MeOC6H4; R1R2NH = Morpholine(l) R = 4-ClC6H4; R1R2NH = Morpholine(m) R = C6H5; R1R2NH = Pyrrolidine(n) R = 4-MeOC6H4; R1R2NH = Pyrrolidine
Scheme 42: Coupling of aldehydes, secondary amines and phenylacetylene catalyzed by Nafion®NR50.
Ph H
R-CHO + R1R2NHN
R
R1 R2
RfSO3-Ph SO3Rf
N
CHR
R1 R2
Ph
H2O
OH-
Rf = CF2-CF2 CF CF2
O CF2 CF O
CF3
n
m+ H
+
Scheme 43: Tentative mechanism for A3-Coupling.
Chapter I
43
EXPERIMENTAL
In a 50 mL round bottom flask, aromatic aldehydes/heterocylic aldehydes (1
mmol), secondary amines (1.2 mmol) and phenylacetylene (1.5 mmol) in CH3CN (5
mL) was taken. To this Nafion®NR50 (0.25 gm) was added and the reaction mixture
was stirred at 70-80 oC for the appropriate time mentioned in Table 4 under nitrogen
atmosphere. The progress of reaction was monitored by TLC. After completion of the
reaction, the reaction mixture was cooled. The organic layer was extracted with
diethyl ether and the remaining Nafion®NR50 was reused for further reactions. The
organic layer was dried over anhydrous Na2SO4 and the solvent was removed in
vacuo. The crude product was subjected to purification by silica gel column
chromatography using 20% ethyl acetate and 80% hexane as an eluent to yield the
propargylamines (115a-n, Table 4). The structures of all the products were
unambiguously established on the basis of their spectral analysis (IR, 1H NMR, 13C
NMR and mass spectral data).
Chapter I
44
Table 1: Optimization of Concentration of Nafion®NR50 for A3-coupling.a
+ + Nafion®NR50, CH3CN70-80 oC, N2 atm.
N
NH
CHO
Entry Catalyst Time (h) Yield (%)b
1 0 18 0
2 0.05 12 83
3 0.10 10 90
4 0.20 5 92
5 0.25 5 96
6 0.35 4 96 aReaction Conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol), Nafion®NR50 (0.05-0.35 gm); solvent CH3CN (5 mL); temperature 70-80 oC, N2 atm. bIsolated yields.
Table 2: Effect of solvent on A3-coupling.a
Entry Solvent Time (h) Yield (%)b
1 Acetonitrile 5 96
2 Methanol 5 92
3 Tetrahydrofuran 5 87
4 Dichloromethane 5 0
5 Dioxane 5 0 aReaction Conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol), Nafion®NR50 (0.25 gm); solvent (5 mL); temperature 70-80 oC, N2 atm. bIsolated yields.
Table 3: Recycling of Nafion®NR50.a
No. of cyclesa Fresh Run 1 Run 2 Run 3 Run 4
Yield (%)b 96 96 95 93 92
Time (h) 5 5 5 5 5 aReaction Conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol), Nafion®NR50 (0.25 gm); solvent CH3CN (5 mL); temperature 70-80 oC, N2 atm. bIsolated yields.
Chapter I
45
Table 4: Nafion®NR50 catalyzed A3-coupling.a
Entry Amine R Product Time (h) Yield (%)b
1 Piperidine C6H5 115a 5.0 96
2 Piperidine 4-MeC6H4 115b 5.5 92
3 Piperidine 4-MeOC6H4 115c 6.0 88
4 Piperidine 4-BrC6H4 115d 4.5 94
5 Piperidine 4-ClC6H4 115e 4.0 93
6 Piperidine 4-O2NC6H4 115f 4.5 95
7 Piperidine 2-Furfuryl 115g 4.0 90
8 Piperidine Cyclohexyl 115h 3.5 88
9 Morpholine C6H5 115i 5.0 85
10 Morpholine 4-MeC6H4 115j 6.5 91
11 Morpholine 4-MeOC6H4 115k 7.0 87
12 Morpholine 4-ClC6H4 115l 4.5 90
13 Pyrrolidine C6H5 115m 6.5 87
14 Pyrrolidine 4-MeOC6H4 115n 7.5 84 aReaction Conditions: aldehydes (1.0 mmol), secondary amines (1.2 mmol), phenylacetylene (1.5 mmol), Nafion®NR50 (0.25 gm); solvent CH3CN (5 mL); temperature 70-80 oC, N2 atm. bIsolated yields.
Chapter I
46
Spectroscopic data of synthesized propargylamines (115a-n)
1-(1,3-Diphenyl-prop-2-ynyl)-piperidine (115a): Yellowish oil; IR (film/cm-1): νmax
= 3051, 2936, 2253, 1617, 1520, 1451, 1320, 1160; 1H NMR (CDCl3, 400 MHz): δ =
7.16-7.35 (m, 10H, 2Ph), 4.56 (s, 1H, CH), 2.56-2.62 (m, 4H, 2CH2), 1.85-1.91 (m,
4H, 2CH2), 1.35-1.50 (m, 2H, CH2); 13C NMR (CDCl3, 100 MHz): δ = 138.7, 132.1,
128.5, 128.2, 128.1, 127.6, 123.4, 88.1, 86.3, 62.5, 50.9, 26.3, 24.5; m/z 275.68 (M+1,
C20H21N requires 275.17).
1-[1-(4-Methylphenyl)-3-phenyl-prop-2-ynyl]-piperidine (115b): Slightly yellowish
oil; IR (film/cm-1): νmax = 2939, 2815, 2278, 1580, 1510, 1319, 1154; 1H NMR (CDCl3,
400 MHz): δ = 7.56-7.61 (m, 9H, 2Ph), 4.78 (s, 1H, CH), 2.52-2.61 (m, 4H, 2CH2), 2.40
(s, 3H, CH3), 1.64-1.73 (m, 4H, 2CH2), 1.45-1.58 (m, 2H, CH2); 13C NMR (CDCl3, 100
MHz): δ = 137.3, 135.8, 132.1, 129.0, 128.7, 128.5, 127.1, 123.6, 87.9, 86.6, 62.8, 62.4,
50.9, 26.4, 24.7, 21.4; m/z 290.19 (M+1, C21H23N requires 289.18).
1-[1-(4-Methoxyphenyl)-3-phenyl-prop-2-ynyl]-piperidine (115c): Slightly yellowish
oil; IR (film/cm-1): νmax = 3015, 2943, 2812, 2203, 1523, 1318, 1168, 1041; 1H NMR
(CDCl3, 400 MHz): δ = 7.69-7.81 (m, 9H, 2Ph), 4.80 (s, 1H, CH), 3.74 (s, 3H, OCH3),
2.55-2.65 (m, 4H, 2CH2), 1.74-1.80 (m, 4H, CH2), 1.45-1.59 (m, 2H, CH2); 13C NMR
(CDCl3, 100 MHz): δ = 158.3, 132.2, 130.4, 129.3, 128.6, 128.2, 123.0, 114.0, 85.6, 82.6,
58.8, 55.3, 26.1, 24.2; m/z 305.90 (M+1, C21H23NO requires 305.18).
1-[1-(4-Bromophenyl)-3-phenyl-prop-2-ynyl]-piperidine (115d): Yellowish oil; IR
(film/cm-1): νmax = 3040, 2955, 2815, 2780, 2270, 1544, 1495, 1314, 1169, 1052; 1H
NMR (CDCl3, 400 MHz): δ = 7.89-7.92 (m, 9H, 2Ph), 4.81 (s, 1H, CH), 2.52-2.66 (m,
4H, 2CH2), 1.66-1.79 (m, 4H, 2CH2), 1.46-1.50 (m, 2H, CH2); 13C NMR (CDCl3, 100
MHz): δ = 138.1, 132.1, 130.1, 128.4, 128.3, 123.1, 121.5, 88.6, 88.5, 61.8, 52.9, 26.3,
24.5; m/z 354.17 (M+1, C20H20NBr requires 353.08).
Chapter I
47
1-[1-(4-Chlorophenyl)-3-phenyl-prop-2-ynyl]-piperidine (115e): Yellowish oil; IR
(film/cm-1): νmax = 3042, 2947, 2811, 2783, 2240, 1549, 1492, 1316, 1167, 1055; 1H
NMR (CDCl3, 400 MHz): δ = 7.84-7.91 (m, 9H, 2Ph), 4.85 (s, 1H, CH), 2.50-2.65
(m, 4H, 2CH2), 1.62-1.71 (m, 4H, 2CH2), 1.43-1.51 (m, 2H, CH2); 13C NMR (CDCl3,
100 MHz): δ = 137.4, 134.2, 131.3, 130.4, 128.4, 128.3, 115.2, 86.9, 80.9, 59.2, 53.3,
25.0, 24.1; m/z 310.17 (M+1, C20H20ClN requires 309.13).
1-[1-(4-Nitrophenyl)-3-phenyl-prop-2-ynyl]-piperidine (115f): Yellowish oil; IR
(film/cm-1): νmax = 2945, 2849, 2190, 1685, 1597, 1334, 1155, 1089; 1H NMR
(CDCl3, 400 MHz): δ = 7.75-7.89 (m, 9H, 2Ph), 4.83 (s, 1H, CH), 2.48-2.59 (m, 4H,
2CH2), 1.55-1.65 (m, 4H, 2CH2), 1.41-1.53 (m, 2H, CH2); 13C NMR (CDCl3, 100
MHz): δ = 138.5, 138.0, 129.7, 128.4, 128.1, 123.6, 122.6, 86.8, 80.0, 59.1, 53.2,
25.3, 24.1; m/z 320.87 (M+1, C20H20N2O2 requires 320.15).
1-[1-(2-Furfuryl)-3-phenyl-prop-2-ynyl]-piperidine (115g): Sticky compound; IR
(film/cm-1): νmax = 2920, 2850, 2367, 2250, 1560, 1314, 1156; 1H NMR (CDCl3, 400
MHz): δ = 7.47-7.52 (m, 5H, Ph), 6.12-6.34 (m, 3H, furfuryl) 4.86 (s, 1H, CH), 2.86-
3.10 (m, 4H, 2CH2), 1.59-1.66 (m, 4H, 2CH2), 1.38-1.50 (m, 2H, CH2); 13C NMR
(CDCl3, 100 MHz): δ 152.5, 142.1, 128.2, 128.3, 122.7, 110.6, 86.8, 80.9, 60.5, 24.7,
24.5; m/z 265.93 (M+1, C18H19NO requires 265.15).
1-[1-(1-Cyclohexyl)-3-phenyl-prop-2-ynyl]-piperidine (115h): Yellowish Oil; IR
(film/cm-1): νmax = 3054, 2842, 2334, 3334, 1585, 1318, 1156, 890; 1H NMR (CDCl3,
400 MHz): δ = 7.52-7.54 (m, 2H, CH2), 7.23-7.26 (m, 3H, CH3), 3.12 (d, J = 8.2Hz,
1H), 2.44-2.65 (m, 4H, CH2), 2.14-2.34 (m, 4H), 2.15-2.19 (m, 2H), 1.70-1.83 (m,
4H), 1.37-1.48 (m, 4H), 1.12-1.35 (m, 3H); 13C NMR (CDCl3, 100 MHz): δ = 131.9,
128.3, 128.0, 122.7, 89.4, 86.6, 64.2, 38.8, 33.1, 30.5, 27.9, 26.0, 25.3, 24.9, 24.5; m/z
282.41 (M+1, C20H27N requires 281.21).
Chapter I
48
1-(1,3-Diphenyl-prop-2-ynyl)-morpholine (115i): Slightly yellowish oil; IR
(film/cm-1): νmax = 3050, 2965, 2301, 1584, 1480, 1320, 1151, 756; 1H NMR (CDCl3,
400 MHz): δ = 7.42-7.70 (m, 10H, 2Ph), 4.83 (s, 1H, CH), 2.94-3.09 (m, 4H, 2CH2),
2.57-2.67 (m, 4H, 2CH2); 13C NMR (CDCl3, 100 MHz): δ = 139.6, 131.2, 128.7,
128.3, 128.1, 127.2, 122.6, 86.7, 80.1, 66.1, 59.3, 52.3; m/z 278.22 (M+1, C19H19NO
requires 277.15).
1-[1-(4-Methylphenyl)-3-phenyl-prop-2-ynyl]-morpholine (115j): Colourless solid,
m. p. 80.5-81.5 oC; IR (film/cm-1): νmax = 3360, 3048, 2972, 2308, 1592; 1H NMR
(CDCl3, 400 MHz): δ = 7.32-7.45 (m, 9H, 2Ph), 4.77 (s, 1H, CH), 3.17-3.22 (m, 4H,
2CH2), 2.54-2.66 (m, 4H, 2CH2), 2.33 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz): δ
= 136.2, 134.7, 128.6, 128.3, 128.2, 122.6, 86.8, 80.9, 66.0, 59.2, 52.2, 21.7. m/z
292.01 (M+1, C20H21NO requires 291.16).
1-[1-(4-Methoxyphenyl)-3-phenyl-prop-2-ynyl]-morpholine (115k): Yellowish oil;
IR (film/cm-1): νmax = 3045, 2962, 2312, 1594, 1349, 1190, 1017, 713; 1H NMR
(CDCl3, 400 MHz): δ = 7.33-7.56 (m, 9H, 2Ph), 4.73 (s, 1H), 3.73-3.89 (m, 3H), 2.16-
2.26 (m, 4H), 1.25-1.56 (m, 4H); 13C NMR (CDCl3, 100 MHz): δ = 159.1, 132.2,
128.8, 128.4, 128.2, 122.6, 112.8, 86.3, 80.6, 66.1, 55.8, 52.3; m/z 307.98 (M+1,
C20H21NO2 requires 307.16).
1-[1-(4-Chlorophenyl)-3-phenyl-prop-2-ynyl]-morpholine (115l): Yellowish oil;
IR (film/cm-1): νmax = 3040, 2965, 1619, 1520, 1411, 1338, 1175, 1069; 1H NMR
(CDCl3, 400 MHz): δ = 7.32-7.50 (m, 9H, 2Ph), 4.62 (s, 1H, CH), 3.47-3.54 (m, 4H,
2CH2), 2.59-2.62 (m, 4H, 2CH2). 13C NMR (CDCl3, 100 MHz): δ = 136.2, 134.7,
131.1, 129.1, 128.6, 122.7, 88.8, 84.3, 67.1, 59.5, 49.6; m/z 312.38 (M+1,
C19H18ClNO requires 311.11).
Chapter I
49
1-(1,3-Diphenyl-prop-2-ynyl)-pyrolidine (115m): Yellowish oil; IR (film/cm-1): νmax
= 3040, 2965, 2807, 2694, 2278, 1619, 1520, 1411, 1338, 1175, 756; 1H NMR
(CDCl3, 400 MHz): δ = 7.58-7.63 (m, 10H, 2Ph), 4.20 (s, 1H, CH), 1.83-2.44 (m, 8H,
4CH2); 13C NMR (CDCl3, 100 MHz): δ = 139.1, 131.0, 128.6, 128.2, 126.8, 123.5,
86.1, 86.0, 59.4, 58.6, 50.5, 23.6; m/z 262.03 (M+1, C19H19N requires 261.15).
1-[1-(4-Methoxyphenyl)-3-phenyl-prop-2-ynyl]-pyrolidine (115n): Yellowish oil;
IR (film/cm-1): νmax = 3076, 2961, 2811, 2646, 1522, 1490, 1348, 1145; 1H NMR
(CDCl3, 400 MHz): δ = 7.59-7.62 (m, 9H, 2Ph), 4.89 (s, 1H, CH), 3.83 (s, 3H), 1.80-
2.62 (m, 8H, 4CH2); 13C NMR (CDCl3, 100 MHz): δ =159.2, 132.2, 129.7, 128.4,
128.3, 122.6, 114.2, 86.0, 80.9, 56.9, 55.2, 23.0; m/z 292.35 (M+1, C20H21NO requires
291.16).
Chapter I
50
REFERENCES
1. S. C. Stinson, Chem. Eng. News, 1982, 60, 22.
2. W. Y. Hsu and T. D. Gierke, J. Membr. Sci., 1983, 13, 307.
3. G. A. Olah, P. S. Iyer and G. K. S. Prakash, Synthesis, 1986, 513.
4. A. Akelah and D. C. Sherrington, Chem. Rev., 1981, 81, 557.
5. G. Gebel, P. Aldebert and M. Pineri, Polymer, 1992, 34, 333.
6. A. M. Affoune, A. Yamada and M. Umeda, J. Power Sources, 2005, 148, 9.
7. Y. Liu, E. Letero and J. G. Goodwin Jr, J. Mol. Catal. A: Chem., 2006, 245,
132.
8. J. M. Aragon, J. M. R. Vegas and L. G. Jodra, Ind. Eng. Chem., 1994, 33, 592.
9. Y. Pouilloux, S. Abro, C. Vanhove and J. Barrault, J. Mol. Catal. A: Chem.,
1999, 149, 243.
10. A. Eisenberg, H. L. Veager, Perfluorinated Ionomer Membranes. ACS
Symposium Series, Vol. 180, American Chemical Society, Washington, DC,
1982, 1.
11. S. C. Yeo and A. Eisenberg, J. Appl. Polym. Sci., 1977, 21, 875.
12. G. A. Olah, J. Kaspi and J. Bukala, J. Org. Chem., 1977, 42, 4187.
13. G. A. Olah, R. Malhotra and S. C. Narang, Synthesis, 1978, 672.
14. G. A. Olah, D. Meidar and J. A. Olah, Nouv. J. Chemie., 1979, 3, 275.
15. H. G. Rajoharison, C. Roussel and J. Metzger, J. Chem. Research (S), 1981,
186.
16. G. A. Olah and A. K. Mehrotra, Synthesis, 1982, 962.
17. G. A. Olah, M. Arvanaghi and V. V. Kishnamurthy, J. Org. Chem., 1983, 48,
3359.
Chapter I
51
18. G. A. Olah, T. Yamato, P. S. Iyer and G. K. S. Prakash, J. Org. Chem., 1986,
51, 2826.
19. G. A. Olah, T. Yamato, P. S. Iyer, N. J. Trivedi, B. P. Singh and G. K. S.
Prakash, Materials Chem. Phy., 1987, 17, 21.
20. M. P. Doyle, M. S. Shanklin, H. Q. Pho and S. N. Mahapatro, J. Org. Chem.,
1988, 53, 1017.
21. T. Yamato, C. Hideshima, M. Tashiro, G. K. S. Prakash and G. A. Olah,
Catal. Lett., 1990, 6, 341.
22. G. K. S. Prakash, P. Ramaiah and R. Krishnamurti, Catal. Lett., 1991, 9, 59.
23. O. Aleksiuk and S .E. Biali, Tetrahedron Lett., 1993, 34, 4857.
24. S. Kobayashi and S. Nagayama, J. Org. Chem., 1996, 61, 2256.
25. G. A. Olah, T. Shamma and G. K. S. Prakash, Catal. Lett., 1997, 46, 1.
26. R. Kumarreswaran, B. G. Reddy and Y. D. Vankar, Tetrahedron Lett., 2001,
42, 7493.
27. S. Rani, J. L. Babu and Y. D. Vankar, Synth. Commun., 2003, 33, 4043.
28. M. A. Zolfigol, I. Mohammadpoor-Baltork, D. Habibi, B. F. Mirjalili and A.
Bamoniri, Phosphorus, Sulfur and Silicon, 2004, 179, 2189.
29. B. V. Lingaiah, G. Ezikiel, T. Yakaiah, G. V. Reddy and P. S. Rao, Synlett, 2006, 2507.
30. H. Lin, Q. Zhao, B. Xu and X. Wang, J. Mol. Catal. A: Chem., 2007, 268,
221.
31. T. Yakaiah, B. P. V. Lingaiah, G. Venkat Reddy, B. Narsaiah and P. Shanthan
Rao, Arkivoc, 2007, (XIII), 227.
32. M. J. Bhanushali, N. S. Nandurkar, M. D. Bhor and B. M. Bhanage, Cat.
Commun., 2008, 9, 425.
33. V. Polshettiwar and R. S. Varma, Tetrahedron Lett., 2008, 49, 879.
Chapter I
52
34. V. Polshettiwar and R. S. Varma, Tetrahedron Lett., 2008, 49, 2661.
35. B. Singh, S. L. Jain, P. K. Khatri and B. Sain, Green Chem., 2009, 11, 1941.
36. M. Kidwai, R. Chauhan and D. Bhatnagar, J. Sulfur Chem., 2011, 32, 37.
37. A. A. Boulton, B. A. Davis, D. A. Durden, L. E. Dyck, A. V. Juorio, X. M. Li,
I. A. Paterson and P. H. Yu, Drug Dev. Res., 1997, 42, 150.
38. N. Shachat and J. J. Bagnell, J. Org. Chem., 1963, 28, 991.
39. M. Chandrasekharam, O. M. Singh, H. Ila and H. Juqjappa, Synth. Commun.,
1998, 16, 3073.
40. J. H. Ahn, M. J. Joung, and N. M. Yoon, J. Org. Chem. 1999, 64, 488.
41. C. Wei and C.-J. Li, J. Am. Chem. Soc., 2002, 124, 5638.
42. N. Gommermann, C. Koradin, K. Polborn and P. Knochel, Angew. Chem. Int.
Ed., 2003, 42, 5763.
43. D. A. Black and B. A. Arndtsen, Org. Lett., 2004, 6, 1107.
44. J. S. Yadav, B. V. S. Reddy, M. Sreenivas and K. Sathaiah, Tetrahedron Lett.,
2005, 46, 8905.
45. C. -H. Ding, D. -D. Chen, Z. -B. Luo, L. -X. Dai and X. -L. Hou, Synlett,
2006, 1272.
46. D. Castagnolo, F. Dessi, M. Radi and M. Botta, Tetrahedron: Asymm. 2007,
18, 1345.
47. M. Kidwai, V. Bansal, A. Kumar and S. Mozumdar, Green Chem., 2007, 9,
742.
48. X. -Y. Chen, X. -L. Qiu and F. -L. Qing, Tetrahedron, 2008, 64, 2301.
49. C. Mukhopadhyay and S. Rana, Catal. Commun., 2009, 11, 285.
50. S. Samai, G. C. Nandi and M. S. Singh, Tetrahedron Lett., 2010, 55, 5555.
Chapter I
53
51. T. Zeng, L. Yang, R. Hudson, G. Song, A. R. Moores and C. -J. Li, Org. Lett.,
2011, 13, 442.
52. D. Prajapati, R. Sarma, D. Bhuyan and W. Hub, Synlett, 2011, 627.
53. L. Abahmane, J. M. Kçhler, G. A. Grob, Chem. Eur. J., 2011, 17, 3005.
54. V. Grinsteins, A. Prikulis, B. Grinberga, H. Uzijs, M. Pakalna and G. Aukone,
Latv. PSR Zinatnu Akademijas Vestis, Kim. Serija, 1976, 3, 299., Chem.
Abstr., 1976, 85, 177223.
55. Z. J. Vejdelek, J. Holubek, M. Bartosova and M. Protiva, Collect. Czech.
Chem. Commun., 1977, 42, 3094.; Chem. Abstr., 1978, 88, 120836.
56. D. J. McNamara, M. E. Berman, D. W. Fry and M. L. Werbel, J. Med. Chem.,
1990, 33, 2045.
57. M. W. Moon, C. G. Chidester, R. F. Heier, J. K. Morris, R. J. Collins, R. R.
Russell, J. W. Francis, G. P. Sage and V. H. Sethy, J. Med. Chem., 1991, 34,
2314.
58. G. Cristalli, R. Volpini, S. Vittori, E. Camaioni, A. Monopoli, A. Conti, S.
Dionisotti, C. Zocchi and E. Ongini, J. Med. Chem., 1994, 37, 1720.
59. N. Pitt and D. Gani, Tetrahedron Lett., 1999, 40, 3811.
60. D. Clark and D. A. Travis, Bioorg. Med. Chem., 2001, 9, 2857.
61. D. A. Burnett, M. A. Caplen, E. M. Browne, H. Zhau, S. W. Altmann, H. R.
Davis and J. W. Clader, Bioorg. Med. Chem. Lett., 2002, 12, 315.; Chem.
Abstr., 2002, 137, 20238.
62. W. Maruyama, M. Weinstock, M. B. H. Youdim, M. Nagai and M. Naoi,
Neurosci. Lett., 2003, 341, 233.
Chapter I
54
63. S. K. Srivastava, M. Jaggi, A. T. Singh, A. Madan, N. Rani, M. Vishnoi, S. K.
Agarwal, R. Mukherjee and A.C. Burman, Bioorg. Med. Chem. Lett., 2007,
17, 6660.; Chem. Abstr., 2007, 148, 100524.
64. M. Kitabatake, J. Nagai, K. Abe, Y. Tsuchiya, K. Ogawa, T. Yokoyama, K.
Mohri, K. Taguchi and Y. Horiguchi, Eur. J. Med. Chem., 2009, 44, 4034.
65. O. Weinreb, T. Amit, O. Bar-Am and M. B. H. Youdim, Prog. Neurobiology,
2010, 92, 330.
66. A. Domling and I. Ugi, Angew. Chem. Intl. Ed., 2000, 39, 3168.
67. S. C. Pan and B. List, Synlett, 2007, 318.
68. G. V. M. Sharma, K. L. Reddy, P. S. Lakshmi and P. R. Krishna, Synthesis,
2006, 55.
69. S. V. Ryabukhin, A. S. Plaskon, E. N. Ostapchuk, D. M. Volochnyuk and A.
A. Tolmachev, Synthesis, 2007, 417.
70. J. Song, H. -W. Shih and L. Deng, Org. Lett., 2007, 9, 603.
71. I. Ugi and C. Steinbruckner, Chem. Ber., 1961, 94, 734.
72. N. Herron and W. E. Farneth, Adv. Mater., 1996, 8, 959.
73. X. Song and A. Sayari, Catal. Rev., 1996, 38, 329.
74. J. H. Clark (Ed.), Catalysis of Organic Reactions by Supported Reagents,
VCH Publishers, NY, USA, 1994, 35.
75. R.A. Sheldon, H.V. Bekkum, Catalysis Through Heterogeneous Catalysis,
Wiley-VCH Publishers, Weinheim, Germany, 2002.
76. A. Corma, Chem. Rev., 1995, 95, 559.
77. I. V. Kozhevnikov, Catal. Rev., 1995, 37, 311.
Chapter I
55
78. (a) D. E. Lopez, J. G. Goodwin Jr. and D. A. Bruce, J. Catal., 2007, 245, 381;
(b) M. Abid, M. Savolainen, S. Landge, J. Hu, G. K. S. Prakash, G. A. Olah
and B. Torok, J. Fluorine Chem., 2007, 128, 587.
79. (a) M. A. Stanescu and R. S. Varma, Tetrahedron Lett., 2002, 43, 7307; (b) M.
A. Zolfigol, I. M. Baltork, D. Habibi, B. F. Mirjalili and A. Bamoniri,
Tetrahedron Lett., 2003, 44, 8165.
80. M. A. Zolfigol, D. Habibi, B. F. Mirjalili and A. Bamoniri, Tetrahedron Lett.,
2003, 44, 3345.
81. (a) For multicomponent reactions, see: Multicomponent Reactions, J. Zhu and
H. Bienayme, Eds., Wiely: Weinheim, 2005, 1; (b) A. Alizadeh Karsalary, M.
R. Mohammadizadeh, A. R. Hasaninejad, A. A. Mohammadi and A. R.
Karimi, J. Iran. Chem. Soc., 2010, 7, 45; (c) B. F. Mirjalilia, A. Bamoniri, M.
A. Karimi Zarchi and H. Emtiazi, J. Iran. Chem. Soc., 2010, 7, 95; (d) F.
Matloubi Moghaddam, H. Saeidian, Z. Mirjafary and A. Sadeghi, J. Iran.
Chem. Soc., 2009, 6, 317; (e) M. Bararjanian, S. Balalaie, B. Movassagh and
A. M. Amani, J. Iran. Chem. Soc., 2009, 6, 436.
82. (a) A. Bisai and V. K. Singh, Org. Lett., 2006, 8, 2405; (b) X. Xu and X. Li,
Org. Lett., 2009, 11, 1027; (c) L. Zani, S. Alesi, P. G. Cozzi and C. Bolm, J.
Org. Chem., 2006, 71, 1558.
83. (a) J. S. Yadav, B. V. S. Reddy, A. V. H. Gopal and K. S. Patil, Tetrahedron
Lett., 2009, 50, 3493; (b) M. L. Kantam, S. Laha , J. Yadav and S. Bhargava,
Tetrahedron Lett., 2008, 49, 3083.
84. (a) D. F. Harvey and D. M. Sigano, J. Org. Chem., 1996, 61, 2268; (b) A.
Furstner, H. Szillat and F. Stelzer, J. Am. Chem. Soc., 2000, 122, 6785; (c) Y.
Yamamoto, H. Hayashi, T. Saigoku and H. Nishiyama, J. Am. Chem. Soc.,
Chapter I
56
2005, 127, 10804; (d) E. -S. Lee, H. -S. Yeom, J. -H. Hwang and S. Shin, Eur.
J. Org. Chem., 2007, 3503; (e) B. Yan and Y. Liu, Org. Lett., 2007, 9, 4323.
85. M. Miura, M. Enna, K. Okuro and M. Nomura, J. Org. Chem., 1995, 60, 4999.
86. (a) M. Konishi, H. Ohkuma, T. Tsuno, T. Oki, G. D. VanDuyne and J. Clardy,
J. Am. Chem. Soc., 1990, 112, 3715; (b) G. Dyker, Angew. Chem. Int. Ed.,
1999, 38, 1698.
87. T. Murai, Y. Mutoh, Y. Ohta and M. Murakami, J. Am. Chem. Soc., 2004,
126, 5968.
88. (a) W. Yan, R. Wang, Z. Xu, J. Xu, L. Lin, Z. Shen and Y. Zhou, J. Mol.
Catal. A: Chem., 2006, 255, 81; (b) Y. Zhang, A. M. Santos, E. Herdtweck, J.
Mink and F. E. Kuhn, New. J. Chem., 2005, 29, 366; (c) C. Wei, Z. Li and C. -
J. Li, Org. Lett., 2003, 5, 4473.
89. (a) M. L. Kantam, B. V. Prakash, C. Reddy, V. Reddy and B. Sreedhar,
Synlett, 2005, 2329; (b) C. Wei and C. -J. Li, J. Am. Chem. Soc., 2003, 125,
9584.
90. V. K. -Y. Lo, Y. Liu, M. -K. Wong and C. -M. Che, Org. Lett., 2006, 8, 1529.
91. (a) L. Shi, Y. -Q. Tu, M. Wang, F. -M. Zhang and C. -A. Fan, Org. Lett. 2004,
6, 1001; (b) S. Orlandi, F. Colombo and M. Benaglia, Synthesis, 2005, 1689;
(c) N. Gommermann and P. Knochel, Chem. Eur. J., 2006, 12, 4380.
92. C. Fischer, E. M. Carreira, Org. Lett., 2001, 3, 4319.
93. L. Pin-Hua and W. Lei, Chin. J. Chem., 2005, 23, 1076.
94. V. K. -Y. Lo, K. K. -Y. Kung, M. -K. Wong and C. -M. Che, J. Organo.
Chem., 2009, 694, 583.
95. Z. Li, C. Wei, L. Chen, R. S. Varma and C. -J. Li, Tetrahedron Lett., 2004, 45,
2443.
Chapter I
57
96. B. M. Choudary, C. Sridhar, M. L. Kantam and B. Sreedhar, Tetrahedron
Lett., 2004, 45, 7319.
97. (a) N. E. Leadbeater, H. M. Torenius and H. Tye, Mol. Diver. 2003, 7, 135; (b)
B. Sreedhar, P. S. Reddy, B. V. Prakash and A. Ravindra, Tetrahedron Lett.,
2005, 46, 7019.
98. S. B. Park and H. Alper, Chem. Commun., 2005, 1315.
99. V. V. Kouznetsov and L. Y. Vargas Mendez, Synthesis, 2008, 491.
100. M. Kidwai, N. K. Mishra, V. Bansal, A. Kumar and S. Mozumdar,
Tetrahedron Lett., 2007, 48, 8883.
101. (a) M. Kidwai, A. Jahan and D. Bhatnagar, J. Sulfur Chem., 2010, 31, 161; (b)
M. Kidwai, A. Jahan and D. Bhatnagar, J. Chem. Sci., 2010, 122, 607; (c) M.
Kidwai, A. Jahan, J. Braz. Chem. Soc., 2010, 21, 2175; (d) M. Kidwai, N. K.
Mishra, D. Bhatnagar and A. Jahan, Green Chem. Lett. Rev., 2011, 4, 109; (e)
M. Kidwai, N. K. Mishra, S. Bhardwaj, A. Jahan, A. Kumar and S.
Mozumdar, Chem. Cat. Chem., 2010, 2, 1312.