Synthesis and Antimicrobial Evaluation of Bisthiazolidinones Built Around Aliphatic Chains

 

Mohamad Yusuf* and Payal Jain

Department of Chemistry, Punjabi University, Patiala-147002, Punjab, India.

*Corresponding Author E-mail: yusuf_sah04@yahoo.co.in

ABSTRACT:

The bisthiazolidinones 3a-3k built around the aliphatic chains ranging from two to twelve carbon units have been synthesized in good yields by refluxing bis-Schiff’s bases 2a-2k with ethyl bromoacetate in dioxane medium. The compounds 2a-2k were obtained from the reaction of bisaldehydes 1a-1k with thiosemicabazide in dry EtOH. The length of the internal spacer did not have any significant effect upon the formation and antimicrobial behavior of the bisthiazolidinones 3a-3k. The structures of the new intermediates 2f, 2h and 2j and final compounds 3a-3k have been determined from the rigorous analysis of their IR, ¹H-NMR, ¹³C-NMR, Mass (ESI) and elemental analysis.

 

 

 

1. INTRODUCTION:

The development of heterocyclic systems of pharmaceutical importance have been of enormous interest to synthetic organic chemist in the past decades. The five membered ring system with more than one heteroatom has been studied previously for many interesting pharmacological properties like anti-inflammatory¹, anti-tubercular², anticancer³, antitumor⁴ and anti-HIV⁵. The Schiff’s bases are also known to possess tranquilizing, muscle relaxant, phychoanalepic, hypnotic, ulcerogenic, antidepressant, antibacterial, antifungal, analgesic and anti-inflammatory properties^6-13. The presence of thiazolidinone moiety in the structure of several naturally occurring molecules is responsible for their important antibiotic, immuno suppressive and antitumor activities^14-17. Bisthiazolidinones are the compounds which are formed by joining two thaizolidinone moieties together through the carbon chains of varying lengths and structures. Some bisheterocycles compounds with suitable alkyl spacer have been studied for some significant activities preferably antitumor¹⁸ and antimicrobial¹⁹. These aspects of the five membered heterocyclic/bisheterocyclic have prompted us to investigate the synthesis and antimicrobial analysis of some bisthiazolidinone 3a-3k. The major interest in this study was to investigate the effect of the internal spacer length upon the synthetic and biological behaviour of final products.

 

2. RESULTS AND DISCUSSION:

The synthesis of bisthiazolidinones 3a-3k was initially started from the O-alkylation of  4-hydroxy-benzaldeyhde in the presence of KOH/EtOH/DMF to give bisaldehydes 1a-1k^21,22 which were further refluxed with thiosemicarbazide in dry EtOH to give bis-Schiff’s bases 2a-2k in good yields. The later compounds were further refluxed for appropriate hours with ethyl bromoacetate by using 1,4-dioxan as a solvent medium to yield bisthiazolidinones 3a-3k. (Scheme-1).

 

The structures of new intermediates 2f, 2h and 2j and bisthiazolidinones 3a-3k were obtained from their spectroscopic data (IR, ¹H and ¹³C-NMR and Mass) and elemental analysis. The physical and spectroscopic data of bis-Schiff’s base 2a-2e, 2g and 2j was in agreement as reported in our earlier study²⁰.

 

The I.R. spectra of 2f, 2h and 2j showed bands at 3310-3180 cm^-1 due to NH stretching and there was no absorption in the C=O group region which indicates that C=O group has undergone transformation during the condensation reaction. Further ¹H-NMR spectra of these compounds (2f, 2h and 2j) produced prominent signals at δ 8.00-7.93 (H-1), 7.61-7.55 (4H, d, J_o=8.8 Hz, H-2’,6’) and 6.89-6.85 (4H, d, J_o=8.8 Hz, H-3’, 5’). The D₂O exchangeable resonance placed at δ 11.27–11.24 and 7.70-7.36 could be assigned to 3-NH and 5-NH₂ group protons. The ¹³C-NMR spectra of 2f, 2h and 2j provided azomethyne carbon (C-1) and thiocarbonyl carbon (C-4) at δ 149-147 and 175-172 respectively. The aromatic ring carbons were also found resonating at the expected position (see experimental).

 

Scheme-1

 

The IR spectra of 3a-3k exhibited major absorption bands at 1620-1610 (C=N), 1172-1162 (C-N) and 1697-1635 cm^-1 (C=O) group. In the ¹H-NMR spectra, the thiazole ring protons (H-4’’) of compounds 3a-3k appeared as singlet in the range 3.98-3.72 ppm. The appearance of sharp singlet at δ 8.09-7.96 could be very well ascribed to azomethyne proton (H-1) and the two doublets in the aromatic region at δ 7.83-7.65 (4H, J_o=8.8 Hz) and 6.97-6.89 (4H, J_o=8.8 Hz) could be denoted by H-2’, 6’ and H-3’, 5’ respectively. The sharp singlet in the range of δ 9.89-9.78 could be resulted by 1’’-NH protons. The signals belonging to (OCH₂) and {(CH₂)_n} group were found placed at δ 4.08-3.88 and 1.99-1.15 respectively with appropriate multiplicity. Regarding the ¹³C-NMR spectra, the peaks at δ 33-29, 163-160 and 173-160 may be assigned to thiazole ring carbons (C-4’’, C-5’’ and 2’’) respectively. The mass spectra and elemental analysis of these compounds also confirmed their structures (see experimental).

 

3. ANTIMICROBIAL ACTIVITY:

The antibacterial activity of compounds 3a-3k were evaluated by disc diffusion method using nutrient broth medium. The bacterial strains used for the activity were Escherichia Coli (MTCC 390), Staphylococcus aureus (MTCC 435), Klubssila pneumoniae (MTCC 3384) and Pseudomonas aeruginosa (MTCC 130). Amoxicillin was taken as the standard drug and DMSO was used as a blank. The culture strains of bacteria were maintained on nutrient agar slant at 37^oC. The antibacterial activity was evaluated using nutrient agar plate seeded with 0.2 ml of respective bacterial culture strain. The compound dissolved in DMSO were poured on the sterile paper disc (5 mm) at conc. 100 μg/ml were used. The above said disc was kept on the surface of solid media which was already inoculated with the bacteria. The plates were incubated for 24 h at 37^oC. The zone of inhibition of compounds in mm was measured and results are shown in Table 1. All the tested compounds showed moderate to low activity against the above said bacteria.

Table 1 Zone of Inhibition (in mm).

Compound No.	E. Coli	Staphylococcus aureus	Klubssila pneumoniae	Pseudomonas
3a	---	7	6	---
3b	----	10	8	9
3c	6	12	7	----
3d	10	----	11	----
3e	9	8	12	----
3f	---	13	----	11
3g	11	-----	10	----
3h	---	12	8	6
Amoxicillin	18	20	17	25

 

 

4. CONCLUSION:

It may be concluded that present study describes an efficient method for the synthesis of some bisthiazolidinones built around the aliphatic carbon chains of varying length under the normal conditions. The antimicrobial behaviour of the bisthiazolidinones is found to be independent of internal spacer length.

 

5. EXPERIMENTAL:

Melting points reported are uncorrected. IR spectra were scanned in KBr pellets on a Perkin Elmer RXIFT Infrared spectrophotometer. ¹H-NMR spectra were recorded on a 400 MHz Bruker spectrometer using TMS as the internal standard. The mass spectra have been scanned on the Waters Micromass Q-T of Micro (ESI) spectrometer. TLC plates were coated with silica gel suspended in MeOH-CHCl₃ and iodine vapours were used as visualizing agent. Bisaldehydes 1a-1k^20-22 and bis-Schiff’s bases 2a-2e, 2g and 2i ²⁰ were prepared according to the reported methods.

 

5.1.1 Synthesis of 1,7-bis-[2-benzylidene-hydrazinecarbothioamide-4’-oxy]heptane 2f:

The bisaldehyde 1f (1.0 g, 0.0029 mol) and thiosemicarbazide (0.536 g, 0.0059 mol) was refluxed for 4 hrs under acidic alcoholic conditions (5ml acid in 20 ml EtOH). The reaction mixture thus obtained was cooled in an ice bath, a solid was separated out. The resulting solid was filtered under suction and crystallized from EtOH to give pure bisthiosemicarbazone 2f.

 

2f: Yellow solid; Yield 61 %; m.p.: 153-155⁰C. IR (KBr) cm^-1 3345 and 3280 (NH₂), 3310 (NH), 2945, 2885 (methylene C-H), 1607 (C=N), 1240, 1027 (C-O); ¹H-NMR (400 MHz, DMSO-d₆):  δ 11.24 (2H, s, 3-NH), 7.98 (2H, s, H-1), 7.55 (4H, d, J_o=8.8 Hz, H-2’, 6’), 7.70 (2H, brs, NH-α), 7.45 (2H, brs, NH-β), 6.87 (4H, d,  J_o=8.9 Hz,   H-3’, 5’), 4.00 (4H, t, J_vic=6.4 Hz, OCH₂CH₂CH₂CH₂), 1.95 (4H, quintet, J_vic=6.3 Hz, OCH₂CH₂CH₂CH₂), 1.52 (4H, m, OCH₂CH₂CH₂CH₂), 1.28 (2H, m, OCH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 175.80 (C-4), 157.59 (C-4’), 149.07 (C-1), 139.60 (C-1’), 130.40 (C-2’, 6’), 115.13 (C-3’, 5’), 68.45 (OCH₂CH₂CH₂CH₂), 28.38 (OCH₂CH₂CH₂CH₂), 28.00 (OCH₂CH₂CH₂CH₂), 25.01 (OCH₂CH₂CH₂CH₂); MS(ESI): m/z (M+1)⁺ 487. Anal. Calc. for C₂₃O₂N₆S₂H₃₀: Calc. C, 56.79 %; H, 6.17 %; N, 17.28 %; Found: C, 56.83 %; H, 6.15%; N, 17.25 %.

 

5.1.2 Synthesis of 1,9-bis-[2-benzylidene-hydrazinecarbothioamide-4’-oxy]nonane 2h:

The bisthiosemicarbazone 2h was synthesized from the reaction of bisaldehyde 1h (1.0 g, 0.0027 mol) with thiosemicarbazide (0.504 g, 0.0054 mol) under the similar conditions as used above for 2f.

 

2h: Yellow solid; Yield 59 %; m.p.: 170-172⁰C. IR (KBr) cm^-1 3361 and 3265 (NH₂), 3260 (NH), 2948, 2881 (methylene C-H), 1602 (C=N), 1248, 1031 (C-O); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.25 (2H, s, 3-NH), 8.00 (2H, s, H-1), 7.60 (4H, d,  J_o=8.7 Hz, H-2’, 6’), 7.65 (2H, brs, NH-α), 7.36 (2H, brs, NH-β), 6.85 (4H, d, J_o=8.7 Hz, H-3’, 5’), 3.98 (4H, t, J_vic=6.4 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.93 (4H, quintet, J_vic=6.4 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.65 (4H, m, OCH₂CH₂CH₂CH₂CH₂), 1.33 (4H, m, OCH₂CH₂CH₂CH₂CH₂), 1.25 (2H, m, OCH₂CH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆):      δ 174.25 (C-4), 154.64 (C-4’), 147.95 (C-1), 139.85 (C-1’), 132.29 (C-2’, 6’), 117.00 (C-3’, 5’), 67.84 (OCH₂CH₂CH₂CH₂CH₂), 28.63 OCH₂CH₂CH₂CH₂CH₂), 28.25 (OCH₂CH₂CH₂CH₂CH₂), 28.12 (OCH₂CH₂CH₂CH₂CH₂), 24.10 (OCH₂CH₂CH₂CH₂CH₂); MS(ESI): m/z (M+K)⁺ 553. Anal.Calc. for C₂₅O₂N₆S₂H₃₄: Calc. C, 58.36 %; H, 6.61 %; N, 16.34 %; Found: C, 58.33 %; H, 6.59 %; N, 16.36 %.

 

5.1.3 Synthesis of 1,11-bis-[2-benzylidene-hydrazinecarbothioamide-4’-oxy]undecane 2j:

The bisthiosemicarbazone 2j was synthesized from the reaction of bisaldehyde 1j (1.0 g, 0.0026 mol) with thiosemicarbazide (0.478 g, 0.0050 mol) under the same conditions as described above for 2f.

 

2j: Yellow solid; Yield 64 %; m.p.: 198-200⁰C. IR (KBr) cm^-1 3355 and 3277 (NH₂), 3180 (NH), 2953, 2889 (methylene C-H), 1605 (C=N), 1231, 1042 (C-O); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.27 (2H, s, 3-NH), 7.93 (2H, s, H-1), 7.61 (4H, d, J_o=8.8 Hz, H-2’, 6’), 7.57 (2H, brs, NH-α), 7.39 (2H, brs, NH-β), 6.89 (4H, d, J_o=8.9 Hz,    H-3’, 5’), 3.99 (4H, t, J_vic=6.3 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.74 (4H, quintet, J_vic=6.3 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.42 (4H, m, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.31 (4H, m, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.29 (6H, m, OCH₂CH₂CH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 172.80 (C-4), 155.20 (C-4’), 148.10 (C-1), 140.15 (C-1’), 132.25 (C-2’, 6’), 115.12 (C-3’, 5’), 67.64 (OCH₂CH₂CH₂CH₂CH₂CH₂), 28.70 OCH₂CH₂CH₂CH₂CH₂CH₂), 28.42 (OCH₂CH₂CH₂CH₂CH₂CH₂), 28.13 (OCH₂CH₂CH₂CH₂CH₂CH₂), 26.70 (OCH₂CH₂CH₂CH₂CH₂CH₂), 25.35 (OCH₂CH₂CH₂CH₂CH₂CH₂); MS(ESI): m/z (M+1)⁺543. Anal.Calc. for C₂₇O₂N₆S₂H₃₈: Calc. C, 59.77 %; H, 7.01 %; N, 15.49%; Found: C, 59.75 %; H, 7.04  %; N, 15.51 %.

 

5.2.1. Synthesis of 1,2-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one] ethane 3a:

A mixture of bisthiosemicarbazone 2a (1.0 g, 0.0026 mol) and ethyl bromoacetate (0.57 ml, 0.0052 mol) was refluxed for 14 hrs in the dioxane. The progress of reaction was monitored by TLC. The resulting reaction mixture was concentrated to half its volume under reduced pressure. The solid product thus obtained was filtered under suction and finally crystallized from MeOH to yield pure bisthiazolidinone 3a.

 

3a: Brown solid; Yield 60 %; m.p.:330-332 ⁰C. IR (KBr) cm^-1 2923, 2852 (methylene C-H), 1697 (C=O), 1610 (C=N), 1250, 1026 (C-O), 1170 (C-N), 721 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.86 (2H, s, H-1’’), 8.09 (2H, s, H-1), 7.78 (4H, d, J_o=8.8 Hz , H-2’, 6’), 6.93 (4H, d, J_o=8.8 Hz, H-3’, 5’), 4.05 (4H, s, J_vic=6.1 Hz, OCH₂); 3.76 (4H, s, H-4’’); ¹³C-NMR (DMSO-d₆): δ 173.00 (C-5’’), 163.05 (C-2’’), 159.8 (C-4’), 149.5 (C-1), 129.8 (C-2’,6’), 125.4 (C-1’), 114.5 (C-3’,5’), 67.80 (OCH₂), 32.5 (C-4’’); MS(ESI): m/z (M+1)⁺ 497. Anal. Calc. for C₂₂O₄N₆S₂H₂₀: Calc. C, 53.22 %; H, 4.03 %; N, 16.93 %; Found: C, 53.40 %; H, 4.00 %; N, 16.95 %.

 

5.2.2. Synthesis of 1,3-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one]  propane 3b:

The compound 3b was prepared by refluxing bisthiosemicarbazone 2b (1.0 g, 0.0025 mol) with ethyl bromoacetate (0.55 ml, 0.0050 mol) under the similar conditions as described above for 3a.

 

3b: Brown solid; Yield 67 %; m.p.: 210-212 ⁰C. IR (KBr) cm^-1 2939, 2862 (methylene C-H), 1639 (C=O), 1613 (C=N), 1245, 1031 (C-O), 1166 (C-N), 734 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.84 (2H, s, H-1’’), 8.06 (2H, s, H-1), 7.73 (4H, d, J_o=8.7 Hz , H-2’, 6’), 6.95 (4H, d, J_o=8.7 Hz, H-3’, 5’), 4.01 (4H, t, J_vic=6.4 Hz, OCH₂CH₂), 1.99 (4H, quintet, J_vic=6.4 Hz, OCH₂CH₂); 3.74 (4H, s, H-4’’); ¹³C-NMR (DMSO-d₆): δ 173.80 (C-5’’), 161.50 (C-2’’), 158.23 (C-4’), 149.0 (C-1), 130.25 (C-1’), 126.25 (C-2’,6’), 114.80 (C-3’,5’), 66.89 (OCH₂CH₂), 33.20 (C-4’’), 28.66 (OCH₂CH₂); MS(ESI): m/z (M+Na)⁺ 533. Anal. Calc. for C₂₃O₄N₆S₂H₂₂: Calc. C, 54.11 %; H, 4.31 %; N, 16.47 %; Found: C, 54.09 %; H, 4.34 %; N, 16.50 %.

 

5.2.3. Synthesis of 1,4-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one] butane 3c:

The compound 3c was synthesized by refluxing bisthiosemicarbazone 2c (1.0 g, 0.0024 mol) with ethyl bromoacetate (0.53 ml, 0.0048 mol) under the similar conditions as described above for 3a.

3c: Yellow solid; Yield 70 %; m.p.: 240-242 ⁰C. IR (KBr) cm^-1  2936, 2863 (methylene C-H),  1635 (C=O),  1615 (C=N), 1246, 1041 (C-O), 1164 (C-N), 731 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.87 (2H, s, H-1’’), 8.03 (2H, s, H-1), 7.75 (4H, d, J_o=8.8 Hz, H-2’, 6’), 6.96 (4H, d, J_o=8.8 Hz, H-3’, 5’), 3.99 (4H, t, J_vic=6.2 Hz, OCH₂CH₂), 1.98 (4H, quintet, J_vic=6.2 Hz, OCH₂CH₂); 3.73 (4H, s, H-4’’); ¹³C-NMR (DMSO-d₆): δ 171.11 (C-5’’), 161.44 (C-2’’), 158.99 (C-4’), 148.09 (C-1), 132.70 (C-1’), 126.05 (C-2’,6’), 114.69 (C-3’,5’), 66.13 (OCH₂CH₂), 35.10 (C-4’’), 26.82 (OCH₂CH₂); MS(ESI): m/z (M+K)⁺ 563. Anal. Calc. for C₂₄O₄N₆S₂H₂₄: Calc. C, 54.96 %; H, 4.58 %; N, 16.03%; Found: C, 54.93 %; H, 4.55 %; N, 16.00 %.

 

5.2.4 Synthesis of 1,5-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one]  pentane 3d:

The compound 3d was obtained by refluxing bisthiosemicarbazone 2d (1.0 g, 0.0023 mol) with ethyl bromoacetate (0.51 ml, 0.0046 mol) under the similar conditions as used earlier for 3a.

 

3d: Yellow solid; Yield 68 %; m.p.: 250-252 ⁰C. IR (KBr) cm^-1 2932, 2852 (methylene C-H), 1638 (C=O), 1612 (C=N), 1242, 1011 (C-O), 1167 (C-N), 733 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ  9.86 (2H, s, H-1’’), 8.05 (2H, s, H-1), 7.72 (4H, d, J_o=8.6 Hz , H-2’, 6’), 6.94 (4H, d, J_o=8.6 Hz, H-3’, 5’), 4.08 (4H, t, J_vic=6.1 Hz, OCH₂CH₂CH₂), 1.96 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂CH₂), 3.88 (4H, s, H-4’’), 1.92 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 171.15 (C-5’’), 160.80 (C-2’’), 158.87 (C-4’), 148.27 (C-1), 132.21 (C-1’), 127.20 (C-2’,6’), 114.35 (C-3’,5’), 67.29 (OCH₂CH₂CH₂), 35.23 (C-4’’), 27.01 (OCH₂CH₂CH₂), 22.75 (OCH₂CH₂CH₂); MS(ESI): m/z (M)⁺ 538. Anal. Calc. for C₂₅O₄N₆S₂H₂₆: Calc. C, 55.76 %; H, 4.83 %; N, 15.61%; Found: C, 55.78 %; H, 4.81 %; N, 15.64 %.

 

5.2.5 Synthesis of 1,6-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one] hexane 3e:

The compound 3e was obtained by refluxing bisthiosemicarbazone 2e (1.0 g, 0.0022 mol) with ethyl bromoacetate (0.48 ml, 0.0044 mol) under the same conditions as used for 3a.

 

3e: Yellow solid; Yield 72 %; m.p.: 258-260 ⁰C. IR (KBr) cm^-1 2929, 2854 (methylene C-H), 1680 (C=O), 1616 (C=N), 1243, 1027 (C-O), 1169 (C-N), 722 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.82 (2H, s, H-1’’), 8.07 (2H, s, H-1), 7.76 (4H, d, J_o=8.9 Hz , H-2’, 6’), 6.92 (4H, d, J_o=8.9 Hz, H-3’, 5’), 4.04 (4H, t, J_vic=6.2 Hz, OCH₂CH₂CH₂), 1.71 (4H, quintet, J_vic=6.2 Hz, OCH₂CH₂CH₂), 3.72 (4H, s, H-4’’), 1.62 (4H, quintet, J_vic=6.2 Hz, OCH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 170.61 (C-5’’), 160.28 (C-2’’), 158.58 (C-4’), 148.01 (C-1), 132.05 (C-1’), 127.08 (C-2’,6’), 113.60 (C-3’,5’), 66.78 (OCH₂CH₂CH₂), 34.13 (C-4’’), 28.07 (OCH₂CH₂CH₂), 24.10 (OCH₂CH₂CH₂); MS(ESI): m/z (M+Na)⁺ 575. Anal. Calc. for C₂₆O₄N₆S₂H₂₈: Calc. C, 56.52 %; H, 5.07 %; N, 15.21%; Found: C, 56.50 %; H, 5.10 %; N, 15.24 %.

5.2.6 Synthesis of 1,7-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one]  heptane 3f:

The compound 3f was synthesized by refluxing bisthiosemicarbazone 2f (1.0 g, 0.0021 mol) with ethyl bromoacetate (0.46 ml, 0.0042 mol) under the same conditions as described earlier for 3a.

 

3f: Brown solid; Yield 62 %; m.p.: 280-282 ⁰C. IR (KBr) cm^-1 2928, 2855 (methylene C-H), 1677 (C=O), 1614 (C=N), 1232, 1031 (C-O), 1165 (C-N), 725 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.81 (2H, s, H-1’’), 7.99 (2H, s, H-1), 7.68 (4H, d, J_o=8.9 Hz, H-2’, 6’), 6.95 (4H, d, J_o=8.9 Hz, H-3’, 5’), 4.00 (4H, t, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂), 1.77 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂), 3.93 (4H, s, H-4’’), 1.68 (4H, m, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂), 1.63 (2H, m, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 170.56 (C-5’’), 160.11 (C-2’’), 156.78 (C-4’), 148.00 (C-1), 132.01 (C-1’), 127.12 (C-2’,6’), 113.40 (C-3’,5’), 66.69 (OCH₂CH₂CH₂CH₂), 34.21 (C-4’’), 28.15 (OCH₂CH₂CH₂CH₂), 27.21 (OCH₂CH₂CH₂CH₂), 25.90 (OCH₂CH₂CH₂CH₂); MS(ESI): m/z (M+1)⁺ 567. Anal. Calc. for C₂₇O₄N₆S₂H₃₀: Calc. C, 57.24 %; H, 5.30 %; N, 14.84%; Found: C, 57.26 %; H, 5.27 %; N, 14.81 %.

 

5.2.7 Synthesis of 1,8-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one]  octane 3g:

The compound 3g was prepared by refluxing bisthiosemicarbazone 2g (1.0 g, 0.0020 mol) with ethyl bromoacetate (0.44 ml, 0.0040 mol) under the similar conditions as described earlier for 3a.

 

3g: Brownish Yellow solid; Yield 80 %; m.p.: 220-222 ⁰C. IR (KBr) cm^-1 2924, 2853 (methylene C-H), 1662 (C=O), 1618 (C=N), 1237, 1032 (C-O), 1168 (C-N), 719 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.89 (2H, s, H-1’’), 7.98 (2H, s, H-1), 7.65 (4H, d, J_o=8.9 Hz, H-2’, 6’), 6.97 (4H, d, J_o=8.9 Hz, H-3’, 5’), 3.97 (4H, t, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂), 1.74 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂), 3.75 (4H, s, H-4’’), 1.50 (4H, m, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂), 1.40 (4H, m, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 168.00 (C-5’’), 162.87 (C-2’’), 154.40 (C-4’), 149.20 (C-1), 128.11 (C-1’), 121.30 (C-2’,6’), 109.68 (C-3’,5’), 67.70 (OCH₂CH₂CH₂CH₂), 31.91 (C-4’’), 27.35 (OCH₂CH₂CH₂CH₂), 27.00 (OCH₂CH₂CH₂CH₂), 25.79 (OCH₂CH₂CH₂CH₂); MS(ESI): m/z (M)⁺ 580. Anal. Calc. for C₂₈O₄N₆S₂H₃₂: Calc. C, 57.93 %; H, 5.51 %; N, 14.48%; Found: C, 57.95 %; H, 5.50 %; N, 14.51 %.

 

5.2.8 Synthesis of 1,9-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one] nonane 3h:

The compound 3h was synthesized by refluxing bisthiosemicarbazone 2h (1.0 g, 0.0019 mol) with ethyl bromoacetate (0.42 ml, 0.0038 mol) under the similar conditions as used for 3a.

 

3h: Brown solid; Yield 64 %; m.p.: 318-320 ⁰C. IR (KBr) cm^-1 2937, 2859 (methylene C-H),  1673 (C=O), 1611 (C=N), 1249, 1039 (C-O), 1171 (C-N), 730 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.82 (2H, s, H-1’’), 8.01 (2H, s, H-1), 7.70 (4H, d, J_o=8.6 Hz , H-2’, 6’), 6.89 (4H, d, J_o=8.6 Hz, H-3’, 5’), 3.93 (4H, t, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.83 (4H, quintet, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 3.98 (4H, s, H-4’’), 1.89 (4H, quintet, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.74 (4H, m, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.25 (2H, m, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 168.18 (C-5’’), 162.65 (C-2’’), 154.12 (C-4’), 149.03 (C-1), 128.79 (C-1’), 121.10 (C-2’,6’), 109.48 (C-3’,5’), 67.65 (OCH₂CH₂CH₂CH₂CH₂), 31.32 (C-4’’), 28.30 (OCH₂CH₂CH₂CH₂CH₂), 27.15 (OCH₂CH₂CH₂CH₂CH₂), 26.89 (OCH₂CH₂CH₂CH₂CH₂), 25.11 (OCH₂CH₂CH₂CH₂CH₂); MS(ESI): m/z (M+K)⁺ 633. Anal. Calc. for C₂₉O₄N₆S₂H₃₄: Calc. C, 58.58 %; H, 5.72 %; N, 14.14 %; Found: C, 58.60 %; H, 5.68 %; N, 14.15 %.

 

5.2.9 Synthesis of 1,10-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one] decane 3i:

The compound 3i was synthesized by refluxing bisthiosemicarbazone 2i (1.0 g, 0.0018 mol) with ethyl bromoacetate (0.39 ml, 0.0036 mol) under the similar conditions as used for 3a.

 

3i: Brown solid; Yield 75 %; m.p.: 340-342 ⁰C. IR (KBr) cm^-1 2930, 2855 (methylene C-H),  1670 (C=O), 1620 (C=N), 1240, 1042 (C-O), 1162 (C-N), 723 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.80 (2H, s, H-1’’), 8.02 (2H, s, H-1), 7.66 (4H, d, J_o=8.6 Hz , H-2’, 6’), 6.90 (4H, d, J_o=8.6 Hz, H-3’, 5’), 3.88 (4H, t, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.76 (4H, quintet, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 3.90 (4H, s, H-4’’), 1.69 (4H, quintet, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.54 (4H, m, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂), 1.29 (4H, m, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 167.29 (C-5’’), 161.84 (C-2’’), 155.03 (C-4’), 147.89 (C-1), 128.01 (C-1’), 119.71 (C-2’,6’), 109.71 (C-3’, 5’), 67.10 (OCH₂CH₂CH₂CH₂CH₂), 29.31 (C-4’’), 28.75 (OCH₂CH₂CH₂CH₂CH₂), 28.56 (OCH₂CH₂CH₂CH₂CH₂), 28.00 (OCH₂CH₂CH₂CH₂CH₂), 24.77 (OCH₂CH₂CH₂CH₂CH₂); MS(ESI): m/z (M+1)⁺ 609. Anal. Calc. for C₃₀O₄N₆S₂H₃₆: Calc. C, 59.21 %; H, 5.92 %; N, 13.81 %; Found: C, 59.18 %; H, 5.88 %; N, 13.78 %.

 

5.2.10 Synthesis of 1,11-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one]  undecane 3j:

The compound 3j was obtained by refluxing bisthiosemicarbazone 2j (1.0 g, 0.0017 mol) with ethyl bromoacetate (0.37 ml, 0.0034 mol) under the same conditions as described for 3a.

 

3j: Brown solid; Yield 58 %; m.p.:222-224 ⁰C. IR (KBr) cm^-1 2938, 2858 (methylene C-H),  1650 (C=O),  1612 (C=N), 1225, 1033 (C-O), 1168 (C-N), 728 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.83 (2H, s, H-1’’), 7.96 (2H, s, H-1), 7.77 (4H, d, J_o=8.8 Hz , H-2’, 6’), 6.91 (4H, d, J_o=8.8 Hz, H-3’, 5’), 4.03 (4H, t, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.82 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂ CH₂CH₂CH₂CH₂), 3.95 (4H, s, H-4’’), 1.75 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.67 (4H, m, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂); 1.17 (6H, m, OCH₂CH₂CH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 167.49 (C-5’’), 161.82 (C-2’’), 155.81 (C-4’), 147.19 (C-1), 128.13 (C-1’), 119.67 (C-2’, 6’), 110.11 (C-3’, 5’), 67.12 (OCH₂CH₂CH₂CH₂CH₂CH₂), 29.13 (C-4’’), 28.78 (OCH₂CH₂CH₂CH₂CH₂CH₂), 28.66 (OCH₂CH₂CH₂CH₂CH₂CH₂), 28.10 (OCH₂CH₂CH₂CH₂CH₂CH₂), 27.68 (OCH₂CH₂CH₂CH₂CH₂CH₂), 24.50 (OCH₂CH₂CH₂CH₂CH₂CH₂); MS(ESI): m/z (M+Na)⁺ 645. Anal. Calc. for C₃₁O₄N₆S₂H₃₈: Calc. C, 59.80 %; H, 6.10 %; N, 13.50 %; Found: C, 59.77 %; H, 6.13 %; N, 13.52 %.

 

5.2.11 Synthesis of 1,12-bis-[4-benzylidene-hydrazinylidene-1,3-thiazolidin-4-one]  dodecane 3k:

The compound 3k was synthesised by refluxing bisthiosemicarbazone 2k (1.0 g, 0.0016 mol) with ethyl bromoacetate (0.35 ml, 0.0032 mol) under the similar conditions as used for 3a.

 

3k: Brown solid; Yield 65 %; m.p.:115-117 ⁰C. IR (KBr) cm^-1  2940, 2860 (methylene C-H),  1667 (C=O), 1617 (C=N), 1230, 1043 (C-O), 1172 (C-N), 720 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 9.78 (2H, s, H-1’’), 8.04 (2H, s, H-1), 7.83 (4H, d, J_o=8.8 Hz , H-2’, 6’), 6.95 (4H, d, J_o=8.8 Hz, H-3’, 5’), 3.89 (4H, t, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.90 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂ CH₂CH₂CH₂CH₂), 3.80 (4H, s, H-4’’), 1.80 (4H, quintet, J_vic=6.1 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂), 1.73 (4H, m, J_vic=6.2 Hz, OCH₂CH₂CH₂CH₂CH₂CH₂); 1.15 (8H, m, OCH₂CH₂CH₂CH₂CH₂CH₂); ¹³C-NMR (DMSO-d₆): δ 166.12 (C-5’’), 160.80 (C-2’’), 154.13 (C-4’), 146.20 (C-1), 128.04 (C-1’), 122.05 (C-2’, 6’), 110.48 (C-3’, 5’), 68.01 (OCH₂CH₂CH₂CH₂CH₂CH₂), 29.01 (C-4’’), 28.40 (OCH₂CH₂CH₂CH₂CH₂CH₂), 28.25 (OCH₂CH₂CH₂CH₂CH₂CH₂), 27.87 (OCH₂CH₂CH₂CH₂CH₂CH₂), 27.40 (OCH₂CH₂CH₂CH₂CH₂CH₂), 24.89 (OCH₂CH₂CH₂CH₂CH₂CH₂); MS(ESI): m/z (M+Na)⁺ 659. Anal. Calc. for C₃₂O₄N₆S₂H₄₀: Calc. C, 60.37 %; H, 6.28 %; N, 13.20 %; Found: C, 60.31 %; H, 6.30 %; N, 13.25 %.

 

6. ACKNOWLEDGEMENT:

Authors are highly thankful to DST (SERC, Fast Track Scheme no. SR/FT/CS-041/2010), New Delhi for providing the financial support for this research work.

 

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Received on 22.04.2011        Modified on 20.05.2011

Accepted on 09.06.2011        © AJRC All right reserved

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