Tetrahedron Letters 52 (2011) 3818–3820

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Tetrahedron Letters

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Efficient synthesis of naphthodiazacrown ethers

Pallavi Singh, Rajiv K. Verma, Maya Shankar Singh ⇑Department of Chemistry (Centre of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi 221005, India

a r t i c l e i n f o a b s t r a c t

Article history:Received 15 March 2011Revised 12 May 2011Accepted 13 May 2011Available online 19 May 2011

Keywords:Naphthodiazacrown ethers2-Hydroxynaphthalene-1-carbaldehydeDihaloelectrophilesa,x-DiaminesMacrocyclization

0040-4039/$ - see front matter � 2011 Elsevier Ltd. Adoi:10.1016/j.tetlet.2011.05.057

⇑ Corresponding author. Fax: +91 542 2368127.E-mail address: mssinghbhu@yahoo.co.in (M.S. Sin

A benign and efficient synthesis of naphthodiazacrown ethers has been described. Reaction of simpledialdehyde precursor with a,x-diamines followed by sodium borohydride reduction leads to 16–27membered naphthodiazacrown ethers in 80–90% yields.

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CHN

CHO

Y NH2H2N

Y

HC

O O

N

DMF

CHO

O O

NaBH4

DMF

K2CO3Br Br

CH2HN

Y

H2C

O O

NH

CHO

OH

+ nn

n=2, A (70%); n=3, B (80%)

nn

Several types of macrocyclic ethers have been designed andcharacterized since the creation of the concept of crown ethersby Pedersen,1 and a series of azacrown ethers have been prepared.2

The field of the macrocyclic chemistry is developing very rapidlybecause of its various applications3,4 including importance in thearea of coordination chemistry5 and its use as urea kinase inhibi-tors.6 Macrocyclic ligands are known to bind metal ions selectively,and are thus employed as carriers in metal selective extraction,phase transfer catalyses, membrane transport and other relatedprocesses.7 Although the interaction of metal ions with the poly-ether crown macrocycles has now been studied in considerabledepth, related studies involving mixed nitrogen–oxygen-donormacrocycles are also receiving increasing attention.8–10 Crownethers incorporating naphthalene residue as part of the macrocycleare interesting metal complexing reagents. The latter macrocyclesmight be expected to span the coordination behavior of the crownpolyethers and the other well-studied group of macrocyclic li-gands, which incorporate only nitrogen donor atoms. In recentyears chiral macrocycles have been reported as host moleculesfor asymmetric catalysis.11,12 Recently, hydroxyazobenzocrownethers as chromoionophores have been reported.13 Furthermore,large crown ethers effectively form interlocked structures like:pseudorotaxanes,14 rotaxanes,15 polyrotaxanes,16 and catenanes.17

Recent years have seen considerable progress in the chemistry ofnaphthodiazacrown ethers related to the development of a newstrategy for their synthesis.

An important challenge in synthesizing macrocyclic systemshaving cavities of various sizes is to tailor reaction conditions to

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gh).

individual substrates. Azo compounds can exist in two isomericforms (Z and E) that make the system even more interesting forphysico-chemical study especially, if the azo group forms part ofa macrocyclic system. Recently, macrocycles having azobenzenechromophores have been synthesized, and their inclusion, gelation,and photochromic properties are studied.8b With this in mind, andin continuation to our methodology for the synthesis of heterocy-cles,18 we decided to investigate the cyclization in one syntheticstep to obtain a range of previously unknown achiral oxazamacro-cycles using aromatic dialdehyde and a,x-diamines. The study ofthe behavior of these compounds as ionophores is ongoing in ourgroup.

The synthetic route to the naphthodiazacrown ethers via aro-matic dialdehydes A and B are shown in Scheme 1. The reactionof 2 equiv of 2-hydroxynaphthalene-1-carbaldehyde with 1 equivof 1,4-dibromobutane and 1,5-dibromopentane afforded O,O’-

EtOH9-16 1-8

Scheme 1. Synthesis of naphthodiazacrown ethers.

Table 1Synthesis of compounds 1–16

Entry Y n Yielda (%)

1 (CH2)2 2 782 (CH2)2 3 753 (CH2)3 2 824 (CH2)3 3 705 (CH2)4 2 826 (CH2)4 3 857 (CH2)3O(CH2)4O(CH2)3 2 808 (CH2)3O(CH2)4O(CH2)3 3 789 (CH2)2 2 8710 (CH2)2 3 8411 (CH2)3 2 8612 (CH2)3 3 8413 (CH2)4 2 8814 (CH2)4 3 9015 (CH2)3O(CH2)4O(CH2)3 2 8716 (CH2)3O(CH2)4O(CH2)3 3 88

a Isolated pure yields.

P. Singh et al. / Tetrahedron Letters 52 (2011) 3818–3820 3819

(1,4-butanediyl)bis-1-formyl-naphthol A and O,O’-(1,5-penta-nediyl)-bis-1-formylnaphthol B, respectively. The structures of Aand B were established from their analytical and spectral (IR, 1H,13C NMR, mass) studies.20

Dialdehydes19,20 A and B on treatment with various aliphatica,x-diamines in hot DMF afforded the macrocyclic diimines 1–8(Table 1).21 The IR spectra of diimines display intense absorptionbands in the region 1630–1640 cm�1 assigned to imine (C@N)bond, and no peak assignable to unreacted amine or carbonylgroups was observed. The 1H NMR spectra of 4 and 8 consist of amultiplet in the region 2.04–2.09 ppm and a triplet at 3.51 ppmfor CH2 and CH2–O–CH2 protons, respectively. A sharp singlet dis-played at 9.00 ppm in compounds 1–8 assigned to azomethine(CH@N) proton. The 13C NMR spectra are in good agreement withsuggested structures of all the synthesized compounds. The signalsin the region 67.4–68.6 ppm were assigned to methylene groupsattached to oxygen atom and signals in the region 56.0–58.2 ppmwere assigned to the signals of methylene groups attached to nitro-gen atoms. Further, reduction of macrocyclic diimines (1–8) wascarried out with excess of NaBH4 in ethanol to afford the desiredmacrocycles 9–16 in excellent yields (Scheme 1, Table 1).22

The 1H and 13C NMR data for compounds 9–16 were consistentwith the proposed structures. It is worth noting that compounds9–16 in their NMR spectra show disappearance of azomethinepeak at 9.00 ppm and appearance of new methylene protons at-tached to naphthalene ring at 4.27 ppm and NH proton at4.23 ppm (D2O exchangeable), suggesting reduction of azomethinegroup. The compounds 9–16 are stabilized by hydrogen bonds in-side the cavity.

In conclusion, we have developed a simple approach for thesynthesis of naphthodiazacrown ethers in high yields from readilyaccessible 2-hydroxynaphthalene-1-carbaldehyde, dihaloalkanes,and a,x-diamines. This approach opens up the way for the synthe-sis of new promising groups of complexing agents and metal ionextractants. We are currently pursuing libraries of macrocyclesbased on this strategy.

Acknowledgments

This work was carried out under financial support from Councilof Scientific and Industrial Research (Grant 01(2260)/08/EMR-II)and Department of Science and Technology (Grant SR/S1/OC-66/2009), New Delhi. P. S. is grateful to UGC for Research Fellowshipand R. K. V. is grateful to Council of Scientific and Industrial Re-search (CSIR), New Delhi for senior research fellowship.

References and notes

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20. General procedure for the synthesis of compounds A and B: To a stirredsuspension of K2CO3 (1.38 g, 10 mmol) in DMF (5 mL) was added a solutionof 2-hydroxynaphthalene-1-carbaldehyde (1.72 g, 10 mmol) in DMF (10 mL)under nitrogen atmosphere. The reaction mixture was further stirred for 2 h.1,4-Dibromo butane (0.6 mL, 5 mmol) or 1,5-dibromopentane (0.7 mL,5 mmol) was added drop-wise to the reaction vessel and the content wasstirred for 12 h. After completion of the reaction (monitored by TLC), thereaction mixture was poured onto crushed ice. A light yellow precipitate wasobtained, which was filtered and washed with water. The crude product waspurified by column chromatography over silica gel using ethyl acetate/n-hexane (1:19) as eluent to give the corresponding dialdehyde in good yield.O,O’-(1,4-butanediyl)bis-1-formylnaphthol (A): yield 2.78 g (70%). mp 198–200 �C. 1H NMR (300 MHz, CDCl3): d = 2.17 (t, J = 6.6 Hz, 4H, CH2CH2), 4.35 (t,J = 6.0 Hz, 4H, OCH2), 7.31–9.26 (m, 12H, ArH), 10.94 (s, 2H, CHO). 13C NMR

3820 P. Singh et al. / Tetrahedron Letters 52 (2011) 3818–3820

(75 MHz, CDCl3): d = 29.1 69.3, 113.4, 116.8, 124.8, 124.9, 128.2, 129.8, 131.3,137.6, 163.5, 191.9. IR (KBr): m = 2938, 1245, 2875, 1668 cm�1. MS (m/z) = 399(M++1). Anal. Calcd for C26H22O4: C, 78.38; H, 5.56. Found: C, 78.64; H, 5.84.O,O’-(1,5- pentanediyl)bis-1-formylnaphthol (B): Yield 3.29 g (80%). mp188–190 �C. 1H NMR (300 MHz, CDCl3): d = 1.79 (s, 2H, CH2), 2.04 (t, J = 6.0 Hz, 4H,CH2), 4.31 (t, J = 9.0 Hz, 4H, OCH2), 7.30–9.28 (m, 12H, ArH), 10.94 (s, 2H, CHO).13C NMR (75 MHz, CDCl3): d = 22.8, 29.1, 69.3, 113.4, 116.8, 124.8, 124.9, 128.2,129.8, 131.5, 137.6, 163.5, 191.9. IR (KBr): m = 3056, 2945, 1670, 1270,1248 cm�1. MS (m/z): 413 (M++1). Anal. Calcd for C27H24O4: C, 78.62; H, 5.86.Found: C, 78.23; H, 6.12.

21. General procedure for the preparation of compounds 1–8: A suspension ofappropriate dialdehyde A or B (1 mmol) in DMF (20 mL) was stirred withheating for 10 min. Thereafter, a,x-diamine (1 mmol) in DMF (5 mL) wasadded very slowly over a period of 10 min at room temperature. The mixturewas stirred for additional 10–12 h at room temperature. After completion ofthe reaction (monitored by TLC), the reaction mixture was poured ontocrushed ice and precipitate obtained was filtered and washed with water to getthe desired product in good yield.

22. General procedure for the preparation of compounds 9–16: In a 50 mL round-bottomed flask, a solution of appropriate diimine (1 mmol) in ethanol (20 mL)was refluxed for 1 h. To this solution, excess of NaBH4 (5 mmol) was added andthe reaction mixture was further refluxed for 4 h. After completion of thereaction (monitored by TLC), the reaction mixture was filtered and volume wasreduced to its half by evaporating the ethanol. Addition of water (40 mL)resulted precipitation, which was filtered and washed with water to get thepure desired product in good yield (Table 1). Data of some selected compounds:

Compound 3: 1H NMR (300 MHz, CDCl3): d = 2.12–2.16 (m, 4H, CH2), 2.41–2.50 (m, 2H, CH2), 3.80 (t, J = 6.0 Hz, 4H, NCH2), 4.29 (t, J = 6.6 Hz, 4H, OCH2),7.38–9.08 (m, 12H, ArH), 9.12 (s, 2H, CH@N). 13C NMR (75 MHz, CDCl3):d = 26.6, 29.9, 58.2, 68.4, 113.3, 118.0, 123.9, 125.5, 127.9, 128.0, 129.1, 132.0,132.2, 157.1, 159.7. IR (KBr): m = 2924, 1631, 1248 cm�1. MS (m/z): 437 (M++1).Anal. Calcd for C29H28N2O2(436.55): C, 79.79; H, 6.46; N, 6.41. Found: C, 80.01;H, 6.12; N, 6.73. Compound 4: 1H NMR (300 MHz, CDCl3): d = 1.95–1.99 (m, 6H,CH2), 2.40–2.56 (m, 2H, CH2), 3.87 (t, J = 5.1 Hz, 4H, NCH2), 4.25 (t, J = 6.6 Hz,4H, OCH2), 7.28–9.03 (m, 12H, ArH), 9.06 (s, 2H, CH@N). 13C NMR (75 MHz,CDCl3): d = 24.0, 29.2, 30.8, 58.5, 69.1, 113.1, 117.9, 123.8, 125.3, 127.7, 127.9,129.0, 131.8, 132.0, 156.7, 159.4. IR (KBr): m = 2931, 1640, 1252, 1089. VS (m/z): 451 (M++1). Anal. Calcd for C30H30N2O2 (450.58): C, 79.97; H, 6.71; N, 6.21.Found: C, 80.36; H, 6.34; N, 6.01. Compound 11: 1H NMR (300 MHz, CDCl3):d = 1.93–2.05 (m, 2H, CH2), 2.18–2.24 (m, 4H, OCH2CH2), 2.91 (t, J = 6.6 Hz, 4H,NCH2), 4.24 (s, 2H, NH), 4.25–4.27 (m, 8H, OCH2 & CH2), 7.35–8.07 (m, 12H,ArH). 13C NMR (75 MHz, CDCl3): d = 26.9, 29.7, 43.3, 47.9, 68.2, 113.4, 121.0,122.9, 123.3, 126.8, 128.4, 129.0, 129.1, 133.2, 154.4. IR (KBr): m = 2924, 1613,1248 cm�1. MS (m/z): 441 (M++1). Anal. Calcd for C29H32N2O2 (440.59): C,79.06; H, 7.32; N, 6.36. Found: C, 79.42; H, 7.43; N, 6.65. Compound 16: 1H NMR(300 MHz, CDCl3): d = 1.92–1.98 (m, 6H, CH2), 2.04–2.08 (m, 8H, CH2), 3.43–3.51 (m, 8H, CH2–O–CH2), 3.87 (t, J = 6.0 Hz, 4H, NCH2), 4.22 (t, J = 6.0 Hz, 4H,NCH2), 4.25 (s, 4H, CH2), 4.71 (s, 2H, NH), 7.30–9.09 (m, 12H, ArH). 13C NMR(75 MHz, CDCl3): d = 22.9, 26.8, 29.2, 30.4, 43.4, 59.3, 67.5, 69.1, 70.7, 113.9,124.0, 125.5, 126.5, 126.9, 127.8, 128.0, 129.2, 132.0, 157.1, 153.6. IR (KBr):m = 2931, 1620, 1248, 1059 cm�1. MS (m/z): 441 (M++1). Anal. Calcd forC37H48N2O4 (584.7): C, 75.99; H, 8.27; N, 4.79. Found: C, 76.12; H, 8.41; N, 4.55.