Note. Synthesis of some new 2-(benzylsulfonylethylsulfonylmethyl)oxazolines. thiazolines

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1 Indian Journal of Chemistry Vol. 51B, ctober 2012, pp Note ynthesis of some new 2-(benzylsulfonylethylsulfonylmethyl)oxazolines and thiazolines V Padmavathi*, C Premakumari, B C Venkatesh, T Bhanu Prakash & A Padmaja Department of Chemistry, ri Venkateswara University, Tirupati , India vkpuram2001@yahoo.com eceived 19 April 2011; accepted (revised) 3 August 2012 A new class of five-membered heterocycles oxazolines and thiazolines have been prepared by multistep, one-pot and microwave irradiation methodologies. The microwave method provides an excellent approach for the safe, rapid, inexpensive and simple synthesis of oxazolines and thiazolines. Keywords: xazolines, thiazolines, samarium(iii) chloride, microwave irradiation The development of five-membered heterocycles adopting simple, facile and efficient methodologies from readily available reagents is one of the major challenges in organic syntheses. Amongst fivemembered heterocycles, 2-oxazolines and 2- thiazolines have attracted a wide range of interest from synthetic and medicinal chemists over the last two decades. xazoline and thiazoline rings are important constituents of bioactive natural products and pharmaceuticals 1 3. everal 2-oxazolines have been used as therapeutic agents. Because of their structural relationship to procaine, 2-oxazoline derivatives might be expected to have local anaesthetic properties 4. In synthesis, 2-oxazolines and 2-thiazolines have been used as building blocks 5-7, protecting groups for β-amino alcohols 8, and as auxiliaries and ligands 9 16 in a number of applications. Moreover, oxazole derivatives have prime importance as azadiene components for Diel s-alder reactions 17,18. A variety of methods have been reported for the synthesis of oxazolines viz., cyclodehydration of amido alcohols 19,20, condensation of imidate- hydrochlorides 21, carboxylic acids 22,23, orthoesters 24,25, imino ether hydrochlorides 26, and nitriles 27,28 with amino alcohols. However, the modified Appel reaction conditions provide a one pot methodology for oxazolines from acids and amino alcohols 29. imilarly, syntheses of thiazolines are reported by the coupling of imidate esters with 2- aminothiols 30,31, cyclodehydration of hydroxy thioamides and heterocyclic interconversions from oxazolines or oxazolidines 39. They can also rely on the formation of an intermediate amide from carboxylic acid and aminoalcohols and its conversion into the corresponding thioamide (obtained by thionation using P 2 5 (ef 40) or Lawesson s reagent 41,42 ), followed by cyclization to thiazoline. esults and Discussion The present communication deals with the synthesis of oxazolines and thiazolines by traditional four-step three intermediate routes, one pot methodology exploiting lanthanide alkoxides and microwave irradiation. The synthetic intermediate benzylsulfonylethylsulfonylacetic acid 6 was prepared as follows. The reaction of benzylthiol with 2-chloroethanol followed by chlorination and oxidation provided 2-chloroethyl benzyl sulfone 4 (ef 43). Treatment of compound 4 with mercaptoacetic acid gave benzylsulfonylethylmercaptoacetic acid 5 which on subsequent oxidation produced 6. Esterification of the latter compound resulted in benzylsulfonylethyl-sulfonylacetic acid methyl ester 7 (cheme I). The reaction of 7 with 2-aminoethanol furnished N- (2-hydroxyethyl) (benzylsulfonylethylsulfonyl)- acetamide 8. Chlorination of 8 with thionyl chloride afforded N-(2-chloroethyl)-2-(benzylsulfonylethylsulfonyl)acetamide 9. Base induced cyclization of 9 with NaH produced 2-(benzylsulfonylethylsulfonylmethyl)oxazoline 10. imilar reaction of 7 with 2- aminoethanethiol gave -(2-aminoethyl)-2-(benzylsulfonylethylsulfonyl)ethanethioate 11 which in the presence of NaH in THF resulted in 2-(benzylsulfonylethylsulfonylmethyl)thiazoline 12 (Method A: cheme II). The compounds 10 and 12 were also prepared by one pot methodology exploiting samarium chemistry. Direct treatment of 7 with 2-aminoethanol in the presence of n-butyllithium complexed with 5-10% molar equivalent of anhydrous samarium chloride suspension in toluene gave 10. Adopting similar methodology, the compound 12 was prepared by the

2 NTE H Cl H 10% NaH 2 H Cl 2 Pyridine 3 Cl H 2 2 AcH 4 Cl H CH NaH, MeH H H 2 2 AcH 5 6 cheme I (a) H (b) CH 3 (c) Cl H 6 H 2 4 MeH 7 Me H + NaMe MeH H N H 8 Cl 2, MeH H, NaMe MeH NH 2 11 NaH, THF Cl N H 9 12 N NaH, THF 10 N cheme II (a) H (b) CH 3 (c) Cl reaction of 7 with 2-aminoethanethiol in the presence of samarium chloride and n-butyllithium (Method B: cheme III). Microwave irradiation provides an alternative to conventional heating as it utilizes the ability of ligands or solids to transfer electromagnetic energy into heat. The time saved by using microwaves is potentially important in traditional organic synthesis. To establish the general validity for the development of oxazolines and thiazolines, one-pot microwave

3 1496 INDIAN J. CHEM., EC B, CTBE H, m(iii)cl 3 H, m(iii)cl 3 7 n-buli, Toluene n-buli, Toluene cheme III H M.W. 6 H H M.W. 12 cheme IV assisted synthesis was carried out. The irradiation of benzylsulfonylethylsulfonylacetic acid 6 and 2- aminoethanol at 540 W for 3 min gave the compound 10. imilarly, the microwave irradiation of compound 6 with 2-aminoethanethiol at 560 W for 4 min resulted in 12. The products 10 and 12 were isolated by solvent extraction and purified by column chromatography to afford pure compounds (Method C: cheme IV). Experimental ection Melting points were determined in open capillaries on a Mel-Temp apparatus and are uncorrected. The homogeneity of the compounds was checked by TLC (silica gel H, BDH, ethyl acetate-hexane, 0.5:2). The I spectra were recorded on a Thermo Nicolet I 200 FT-I spectrometer as KBr pellets and the wave numbers were given in cm -1. The 1 H NM spectra were recorded in CDCl 3 / DM-d 6 on a Jeol JNM λ- 400 MHz machine. The 13 C NM spectra were recorded in CDCl 3 / DM-d 6 on a Jeol JNM spectrometer operating at 100 MHz. All chemical shifts are reported in δ (ppm) using TM as an internal standard. The microanalyses were performed on Perkin-Elmer 240C elemental analyzer. The microwave irradiation was carried out by using scientific microwave system CATA-2 operating at power levels from 140 W to 700 W. Built-in magnetic stirring (Teflon-coated stirring bar) was used in all operations. The temperature was measured by flexible probe throughout the reaction. Method A General method for the preparation of benzylsulfonylethylmercaptoacetic acid, 5 To a solution of sodium hydroxide (0.01 mol) in methanol (3 ml) mercaptoacetic acid (0.005 mol) was added slowly. After complete addition 2-chloroethyl benzyl sulfone 4 (0.005 mol) was added portionwise. The reaction mixture was refluxed for 3-4 hr, cooled and poured into crushed ice containing conc. HCl. The separated solid was filtered and dried. The resultant compound was purified by recrystallization from water. Benzylsulfonylethylmercaptoacetic acid, 5a: White solid, yield 67%, m.p C. I (KBr): 1150, 1328 ( 2 ), 1710 (C=), 3328 (H) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 3.42 (t, 2H, J = 4.6 Hz, -), 3.73 (t, 2H, J = 4.6 Hz, 2 - ), 3.82 (s, 2H, -C), 4.38 (s, 2H, Ar- ), (m, 5H, Ar-H), (bs, 1H, H); 13 C NM (100 MHz, CDCl 3 ): δ 45.2 ( -), 47.4 ( 2 - ), 56.5 ( - C), 57.8 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). 4-Methylbenzylsulfonylethylmercaptoacetic acid, 5b: White solid, yield 65%, m.p C. I (KBr): 1148, 1324 ( 2 ), 1708 (C=), 3325 (H) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 3.40 (t, 2H, J = 4.5 Hz, -), 3.71 (t, 2H, J = 4.5 Hz, 2 - ), 3.75 (s, 2H, -C), 4.34 (s, 2H, Ar- ), (m, 4H, Ar- H), (bs, 1H, H); 13 C NM (100 MHz, CDCl 3 ): δ 45.0 ( -), 47.2 ( 2 - ) 56.3 ( -C), 57.5 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). 4-Chlorobenzylsulfonylethylmercaptoacetic acid, 5c: White solid, yield 72%, m.p C. I (KBr): 1156, 1336 ( 2 ), 1718 (C=), 3335 (H) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 3.48 (t, 2H, J = 4.7 Hz, -), 3.65 (t, 2H, J = 4.7 Hz, 2 - ), 3.85 (s, 2H, -C), 4.41 (s, 2H, Ar- ), (m, 4H, Ar- H), (bs, 1H, H); 13 C NM (100 MHz, CDCl 3 ): δ 45.6 ( -), 47.8 ( 2 - ) 56.9 ( -C), 58.2 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C).

4 NTE 1497 General method for the preparation of benzylsulfonylethylsulfonylacetic acid, 6 An ice-cold solution of benzylsulfonylethylmercaptoacetic acid 5 (0.005 mol) in glacial acetic acid (3 ml) was treated with 30% hydrogen peroxide (1.3 ml) in portions. The contents were allowed to attain laboratory temperature and then refluxed for 1-2 hr. The reaction mixture was cooled and acetic acid was removed in vacuo. The residual portion was poured onto crushed ice and the product obtained was collected by filtration. It was washed with cold water and dried. The crude compound was purified by recrystallization from water. Benzylsulfonylethylsulfonylacetic acid, 6a: White solid, yield 65%, m.p C. I (KBr): 1152, 1335 ( 2 ), 1713 (C=), 3331 (H) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 3.48 (t, 2H, J = 4.5 Hz, - 2 ), 3.78 (t, 2H, J = 4.5 Hz, 2 - ), 3.91 (s, 2H, - C), 4.45 (s, 2H, Ar- ), (m, 5H, Ar-H), (bs, 1H, H); 13 C NM (100 MHz, CDCl 3 ): δ 45.4 ( 2 - ), 47.9 ( - 2 ), 57.5 ( -C), 58.8 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). 4-Methylbenzylsulfonylethylsulfonylacetic acid, 6b: White solid, yield 67%, m.p C. I (KBr): 1149, 1351 ( 2 ), 1710 (C=), 3338 (H) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 2.29 (s, 3H, Ar-CH 3 ), 3.50 (t, 2H, J = 4.6 Hz, - 2 ), 3.75 (t, 2H, J = 4.6 Hz, 2 - ), 3.89 (s, 2H, -C), 4.48 (s, 2H, Ar- ), (m, 4H, Ar-H), (bs, 1H, H); 13 C NM (100 MHz, CDCl 3 ): δ 22.1 (ArCH 3 ), 45.1 ( 2 - ), 47.7 ( - 2 ), 57.4 ( -C), 58.9 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). 4-Chlorobenzylsulfonylethylsulfonylacetic acid, 6c: White solid, yield 70%, m.p C. I (KBr): 1155, 1357 ( 2 ), 1715(C=), 3341 (H) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 3.51 (t, 2H, J = 4.7 Hz, - 2 ), 3.79 (t, 2H, J = 4.7 Hz, 2 - ), 3.90 (s, 2H, -C), 4.50 (s, 2H, Ar- ), (m, 4H, Ar-H), (bs, 1H, H); 13 C NM (100 MHz, CDCl 3 ): δ 45.9 ( 2 - ), 47.5 ( - 2 ), 57.0 ( -C), 58.4 (Ar- ), (Ar-C), (Ar- C), (Ar-C), (Ar-C), (C). General method for the preparation of benzylsulfonylethylsulfonylacetic acid methyl esters, 7 A solution of benzylsulfonylethylsulfonylacetic acid 6 (0.01 mol) in methanol (10 ml) and conc. H 2 4 (1 ml) was refluxed on steam bath for 8-10 hr. The contents of the flask were cooled and poured onto crushed ice. The crude product was purified by recrystallization from methanol to get 7. Benzylsulfonylethylsulfonylacetic acid methyl ester, 7a: White solid, yield 67%, m.p C. I (KBr): 1150, 1330 ( 2 ), 1740 (C=) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 3.54 (t, 2H, J = 4.8 Hz, - 2 ), 3.69 (t, 2H, J = 4.8 Hz, 2 - ), 3.83 (s, 3H, -CH 3 ), 4.02 (s, 2H, -C), 4.68 (s, 2H, Ar- ), (m, 5H, Ar-H); 13 C NM (100 MHz, CDCl 3 ): δ 46.4 ( 2 - ), 47.2 ( - 2 ), 54.0 (- CH 3 ), 57.8 ( -C), 61.3 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). 4-Methylbenzylsulfonylethylsulfonylacetic acid methyl ester, 7b: White solid, yield 68%, m.p C. I (KBr): 1142, 1320 ( 2 ), 1730 (C=) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 2.31 (s, 3H, Ar-CH 3 ), 3.56 (t, 2H, J = 5.1 Hz, - 2 ), 3.71 (t, 2H, J = 5.1 Hz, 2 -), 3.87 (s, 3H, -CH 3 ), 4.09 (s, 2H, - C), 4.61 (s, 2H, Ar- ), (m, 4H, Ar-H); 13 C NM (100 MHz, CDCl 3 ): δ 21.8 (Ar-CH 3 ), 46.0 ( 2 - ), 47.5 ( - 2 ), 54.2 (-CH 3 ), 58.0 ( -C), 61.0 (Ar- ), (Ar-C), (Ar- C), (Ar-C), (Ar-C), (C). 4-Chlorobenzylsulfonylethylsulfonylacetic acid methyl ester, 7c: White solid, yield 70%, m.p C. I (KBr): 1138, 1310 ( 2 ), 1725 (C=) cm -1 ; 1 H NM (400 MHz, CDCl 3 ): δ 3.52 (t, 2H, J = 4.9 Hz, - 2 ), 3.68 (t, 2H, J = 4.9 Hz, 2 - ), 3.85 (s, 3H, -CH 3 ), 4.06 (s, 2H, -C), 4.65 (s, 2H, Ar- ), (m, 4H, Ar-H); 13 C NM (100 MHz, CDCl 3 ): δ 46.8 ( 2 - ), 47.8 ( - 2 ), 54.8 (-CH 3 ), 58.5 ( -C), 61.8 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar- C), (C). General method for the preparation of N-(2- hydroxyethyl)-2-(benzylsulfonylethylsulfonyl)- acetamides, 8 A mixture of benzylsulfonylethylsulfonylacetic acid methyl ester 7 (0.01 mol), 2-aminoethanol (0.01 mol), methanol (5 ml) and NaMe (0.01 mol) was refluxed for 7-10 hr. The solution was concentrated, cooled and poured onto crushed ice. The solid separated was filtered, dried and recrystallized from methanol to give 8. N-(2-Hydroxyethyl)-2-(benzylsulfonylethylsulfonyl)acetamide, 8a: White solid, yield 68%, m.p C. I (KBr): 1130, 1302 ( 2 ), 1640 (C=), 3325 (NH), 3380 (H) cm -1 ; 1 H NM (400 MHz, DMd 6 ): δ 3.45 (t, 2H, J = 5.3 Hz, NH- ), 3.56 (t, 2H,

5 1498 INDIAN J. CHEM., EC B, CTBE 2012 J = 5.3 Hz, -H), 3.63 (t, 2H, J = 4.9 Hz, - 2 ), 3.75 (t, 2H, J = 4.9 Hz, 2 - ), 4.24 (s, 2H, -C), 4.69 (s, 2H, Ar- ), 4.76 (br,1h, H), (m, 5H, Ar-H), 8.40 (br, 1H, NH); 13 C NM (100 MHz, DM-d 6 ): δ 41.9 (NH- ), 47.1 ( 2 - ), 47.6 ( - 2 ), 58.1 ( -C), 59.4 ( -H), 66.0 (Ar- ), (Ar-C), (Ar- C), (Ar-C), (Ar-C), (C). N-(2-Hydroxyethyl)-2-(4-methylbenzylsulfonylethylsulfonyl)acetamide, 8b: White solid, yield 71%, m.p C. I (KBr): 1127, 1310 ( 2 ), 1630 (C=), 3330 (NH), 3376 (H) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 2.33 (s, 3H, Ar-CH 3 ), 3.42 (t, 2H, J = 5.0 Hz, NH- ), 3.59 (t, 2H, J = 5.0 Hz, - H), 3.64 (t, 2H, J = 4.6 Hz, - 2, ), 3.77 (t, 2H, J = 4.6 Hz, 2 -, ), 4.22 (s, 2H, -C), 4.58 (s, 2H, Ar- ), 4.74 (br, 1H, H), (m, 4H, Ar-H), 8.42 (br, 1H, NH); 13 C NM (100 MHz, DM-d 6 ): δ 23.4 (Ar-CH 3 ), 41.6 (NH- ), 47.2 ( 2 - ), 47.8 ( - 2 ), 58.0 ( -C), 59.7 ( -H), 66.4 (Ar- ), (Ar-C), (Ar- C), (Ar-C), (Ar-C), (C). N-(2-Hydroxyethyl)-2-(4-chlorobenzylsulfonylethylsulfonyl)acetamide, 8c: White solid, yield 66%, m.p C. I (KBr): 1123, 1314 ( 2 ), 1635 (C=), 3315 (NH), 3369 (H) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 3.49 (t, 2H, J = 5.1 Hz, NH- ), 3.55 (t, 2H, J = 5.1 Hz, -H), 3.61 (t, 2H, J = 4.7 Hz, - 2 ), 3.73 (t, 2H, J = 4.7 Hz, 2 - ), 4.22 (s, 2H, -C), 4.55 (s, 2H, Ar- ), 4.71 (br, 1H, H), (m, 4H, Ar-H), 8.39 (br,1h, NH); 13 C NM (100 MHz, DM-d 6 ): δ 41.8 (NH- ), 47.0 ( 2 - ), 48.2 ( - 2 ), 58.2 ( -C), 59.3 ( -H), 66.6 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). General method for the preparation of N-(2-chloroethyl)-2-(benzylsulfonylethylsulfonyl)- acetamides, 9 The compound N-(2-hydroxyethyl)-2-(benzylsulfonylethylsulfonyl) acetamide 8 (0.01 mol), thionyl chloride (0.015 mol) and methanol (10 ml) were refluxed for hr. It was cooled and poured onto crushed ice. The solid separated was filtered, dried and purified by recrystallization from methanol to give 9. N-(2-Chloroethyl)-2-(benzylsulfonylethylsulfonyl)- acetamide, 9a: White solid, yield 63%, m.p C. I (KBr): 1140, 1312 ( 2 ), 1670 (C=), 3320 (NH) cm -1 ; 1 H NM (400 MHz, DM-d 6 ) δ 3.44 (t, 2H, J = 5.0 Hz, NH- ), 3.50 (t, 2H, J = 5.0 Hz, -Cl), 3.54 (t, 2H, J = 4.3 Hz, - 2 ), 3.67 (t, 2H, J = 4.3 Hz, 2 - ), 4.12 (s, 2H, -C), 4.62 (s, 2H, Ar- ), (m, 5H, Ar-H), 8.30 (br, 1H, NH); 13 C NM (100 MHz, DM-d 6 ): δ 44.7 (NH- ), 46.0 ( 2 - ), 47.2 ( - 2 ), 49.3 ( -Cl), 57.8 ( - C), 61.9 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). N-(2-Chloroethyl)-2-(4-methylbenzylsulfonylethylsulfonyl)acetamide, 9b: White solid, yield 65%, m.p C. I (KBr): 1134, 1310 ( 2 ), 1675 (C=), 3310 (NH) cm -1 ; 1 H NM (400 MHz, DM-d 6 ) δ 2.30 (s, 3H, Ar-CH 3 ), 3.41 (t, 2H, J = 4.8 Hz, NH- ), 3.46 (t, 2H, J = 4.8 Hz, -Cl), 3.53 (t, 2H, J = 4.5 Hz, - 2 ), 3.62 (t, 2H, J = 4.5 Hz, 2 - ), 4.09 (s, 2H, -C), 4.58 (s, 2H, Ar- ), (m, 4H, Ar-H), 8.25 (br, 1H, NH); 13 C NM (100 MHz, DM-d 6 ): δ 20.8 (Ar-CH 3 ), 44.5 (NH- ), 46.2 ( 2 - ), 47.0 ( - 2 ), 48.5 ( -Cl), 57.6 ( -C), 61.7 (Ar- ), (Ar- C), (Ar-C), (Ar-C), (Ar-C), (CNH). N-(2-Chloroethyl)-2-(4-chlorobenzylsulfonylethylsulfonyl)acetamide, 9c: White solid, yield 69%, m.p C. I (KBr): 1132, 1303 ( 2 ), 1660 (C=), 3330 (NH) cm -1 ; 1 H NM (400 MHz, DMd 6 ): δ 3.40 (t, 2H, J = 5.1 Hz, NH-, ), 3.44 (t, 2H, J = 5.1 Hz, -Cl), 3.52 (t, 2H, J = 4.3 Hz, - 2 ), 3.64 (t, 2H, J = 4.3 Hz, 2 - ), 4.10 (s, 2H, - C), 4.60 (s, 2H, Ar- ), (m, 4H, Ar-H), 8.27 (br, 1H, NH); 13 C NM (100 MHz, DM-d 6 ): δ 44.2 (NH- ), 46.8 ( 2 - ), 47.5 ( - 2 ), 49.1 ( -Cl), 57.4 ( -C), 62.2 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (CNH). General method for the preparation of 2-(benzylsulfonylethylsulfonylmethyl)oxazolines, 10 To a solution of N-(2-chloroethyl)-2-(benzylsulfonylethylsulfonyl)acetamide 9 (0.001 mol) in tetrahydrofuran (3 ml), a catalytic amount of sodium hydride was added and refluxed for 4-7 hr. The reaction mixture was allowed to attain T and poured onto crushed ice. The solid obtained was filtered, dried and purified by recrystallization from methanol to give (Benzylsulfonylethylsulfonylmethyl)oxazoline, 10a: White solid, yield 68%, m.p C. I (KBr): 1132, 1325 ( 2 ), 1580 (C=N) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 2.76 (t, 2H, J = 5.6 Hz, C 4 -

6 NTE 1499 H), 3.57 (t, 2H, J = 5.6 Hz, C 5 -H), 3.64 (t, 2H, J = 5.0 Hz, - 2 ), 3.69 (t, 2H, J = 5.0 Hz, 2 - ), 3.79 (s, 2H, -C=), 4.65 (s, 2H, Ar- ), (m, 5H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 45.1 ( 2 - ), 47.0 ( - 2 ), 53.2 (C-4), 55.0 ( -C=), 59.6 (Ar- ), 66.3 (C-5), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C- 2). Anal. Calcd for C 13 H 17 N 5 2 : C, 47.11; H, 5.16; N, Found: C, 47.20; H, 5.21; N, 4.28%. 2-(4-Methylbenzylsulfonylethylsulfonylmethyl)- oxazoline, 10b: White solid, yield 67%, m.p C. I (KBr): 1130, 1318 ( 2 ), 1575 (C=N) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 2.34 (s, 3H, Ar- CH 3 ), 2.81 (t, 2H, J = 5.3 Hz, C 4 -H), 3.49 (t, 2H, J = 5.3 Hz, C 5 -H), 3.61 (t, 2H, J = 5.1 Hz, - 2 ), 3.65 (t, 2H, J = 5.1 Hz, 2 -,), 3.74 (s, 2H, -C=), 4.68 (s, 2H, Ar- ), (m, 4H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 22.4 (Ar-CH 3 ), 45.3 ( 2 - ), 46.9 ( - 2 ), 52.7 (C-4), 55.3 ( - C=), 60.1 (Ar- ), 65.6 (C-5), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C-2). Anal. Calcd for C 14 H 19 N 5 2 : C, 48.67; H, 5.54; N, Found: C, 48.67; H, 5.59; N, 4.11%. 2-(4-Chlorobenzylsulfonylethylsulfonylmethyl)- oxazoline, 10c: White solid, yield 69%, m.p C. I (KBr): 1134, 1312 ( 2 ), 1570 (C=N) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 2.76 (t, 2H, J = 5.5 Hz, C 4 -H), 3.51 (t, 2H, J = 5.5 Hz, C 5 -H), 3.62 (t, 2H, J = 5.3 Hz, - 2 ), 3.68 (t, 2H, J = 5.3 Hz, 2 - ), 3.74 (s, 2H, -C=), 4.62 (s, 2H, Ar- ), (m, 4H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 44.9 ( 2 - ), 47.2 ( - 2 ), 52.9 (C-4), 55.8 ( -C=), 59.8 (Ar- ), 66.0 (C-5), (Ar-C), (Ar-C), (Ar-C), (Ar- C), (C-2). Anal. Calcd for C 13 H 16 ClN 5 2 : C, 42.67; H, 4.40; N, Found: C, 42.71; H, 4.46; N, 3.87%. General method for the preparation of -(2- aminoethyl)-2-(benzylsulfonylethylsulfonyl)ethanethioates, 11 A mixture of benzylsulfonylethylsulfonylacetic acid methyl ester 7 (0.001 mol), 2-aminoethanethiol ( mol), methanol (5 ml) and NaMe (0.001 mol) was refluxed for 3-5 hr. The solution was cooled and poured onto crushed ice. The solid separated was filtered, dried and purified by recrystallization from methanol to give 11. -(2-Aminoethyl)-2-(benzylsulfonylethylsulfonyl)ethanethioate, 11a: White solid, yield 64%, m.p C. I (KBr): 1123, 1340 ( 2 ), 1655 (C=), 3322, 3330 ( ) cm -1 ; 1 H NM (400 MHz, DMd 6 ): δ 3.23 (t, 2H, J = 5.2 Hz, - ), 3.42 (t, 2H, J = 5.2 Hz, - ), 3.61 (t, 2H, J = 4.5 Hz, - 2 ), 3.70 (t, 2H, J = 4.5 Hz, 2 - ), 4.15 (s, 2H, -C), 4.60 (s, 2H, Ar- ), 5.48 (s, 2H, ), (m, 5H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 48.1 ( - ), 50.8 (- ), 52.4 ( 2 - ), 53.5 ( - 2 ), 61.5 (Ar- ), 63.2 ( -C), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). -(2-Aminoethyl)-2-(4-methylbenzylsulfonylethylsulfonyl)ethanethioate, 11b: White solid, yield 67%, m.p C. I (KBr): 1126, 1339 ( 2 ), 1650 (C=), 3328, 3338 ( ) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 2.26 (s, 3H, Ar-CH 3 ), 3.26 (t, 2H, J = 5.3 Hz, - ), 3.44 (t, 2H, J = 5.3 Hz, - ), 3.57 (t, 2H, J = 4.6 Hz, - 2 ), 3.73 (t, 2H, J = 4.6 Hz, 2 - ), 4.12 (s, 2H, -C), 4.59 (s, 2H, Ar- ), 5.40 (s, 2H, ), (m, 4H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 22.8 (Ar- CH 3 ), 48.3 ( - ), 49.9 (- ), 52.2 ( 2 - ), 53.2 ( - 2 ), 61.9 (Ar- ), 62.9 ( - C), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). -(2-Aminoethyl)-2-(4-chlorobenzylsulfonylethylsulfonyl)ethanethioate, 11c: White solid, yield 63%, m.p C. I (KBr): 1130, 1333 ( 2 ), 1645 (C=), 3325, 3334 ( ) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 3.27 (t, 2H, J = 5.2 Hz, - ), 3.45 (t, 2H, J = 5.2 Hz, -, ), 3.62 (t, 2H, J = 4.5 Hz, 2 ), 3.68 (t, 2H, J = 4.5 Hz, 2 - ), 4.20 (s, 2H, -C), 4.55 (s, 2H, Ar- ), 5.53 (s, 2H, ), (m, 4H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 48.5 ( - ), 50.4 (- ), 52.7 ( 2 - ), 53.0 ( - 2 ), 62.2 (Ar- ), 63.0 ( -C), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C). General method for the preparation of 2- (benzylsulfonylethylsulfonylmethyl)thiazolines, 12 To a solution of -(2-aminoethyl)-2-(benzylsulfonylethylsulfonyl)ethanethioate 11 (0.002 mol) in tetrahydrofuran (6 ml), a catalytic amount of sodium hydride was added and refluxed for 7-10 hr. The reaction mixture was concentrated, cooled and poured onto crushed ice. The solid obtained was filtered, dried and purified by recrystallization from methanol to give (Benzylsulfonylethylsulfonylmethyl)thiazoline, 12a: White solid, yield 68%, m.p C. I

7 1500 INDIAN J. CHEM., EC B, CTBE 2012 (KBr): 1140, 1325 ( 2 ), 1550 (C=N) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 2.82 (t, 2H, J = 5.6 Hz, C 5 -H); 3.25 (t, 2H, J = 5.6 Hz, C 4 -H), 3.67 (t, 2H, J = 5.2 Hz, - 2 ), 3.70 (t, 2H, J = 5.2 Hz, 2 - ), 3.77 (s, 2H, -C=), 4.61 (s, 2H, Ar- ), (m, 5H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 36.2 (C-5), 45.3 ( 2 - ), 46.4 ( - 2 ), 57.2 (C-4), 58.6 ( -C=), 62.0 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C-2). Anal. Calcd for C 13 H 17 N 4 3 : C, 44.93; H, 4.93; N, Found: C, 45.05; H, 4.97; N, 4.09%. 2-(4-Methylbenzylsulfonylethylsulfonylmethyl)- thiazoline, 12b: White solid, yield 66%, m.p C. I (KBr): 1138, 1320 ( 2 ), 1555 (C=N) cm -1 ; 1 H NM (400 MHz, DM-d 6 ): δ 2.38 (s, 3H, Ar- CH 3 ), 2.80 (t, 2H, J = 5.7 Hz, C 5- H), 3.29 (t, 2H, J = 5.7 Hz, C 4 -H), 3.64 (t, 2H, J = 5.3Hz, - 2 ), 3.68 (t, 2H, J = 5.3 Hz, 2 - ), 3.74 (s, 2H, -C=), 4.58 (s, 2H, Ar- ), (m, 4H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 22.3 (Ar-CH 3 ), 36.5 (C-5), 45.7 ( 2 - ), 46.5 ( - 2 ), 57.0 (C-4), 57.5 ( -C=), 61.8 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C-2). Anal. Calcd for C 14 H 19 N 4 3 : C, 46.51; H, 5.29; N, Found: C, 46.43; H, 5.34; N, 3.93%. 2-(4-Chlorobenzylsulfonylethylsulfonylmethyl)- thiazoline, 12c: White solid, yield 65%, m.p C. I (KBr): 1135, 1345 ( 2 ), 1560 (C=N) cm -1 ; 1 H NM (400 MHz, DM-d 6 ) δ 2.78 (t, 2H, J = 5.8 Hz, C 5 -H), 3.31 (t, 2H, J = 5.8 Hz, C 4 -H), 3.62 (t, 2H, J = 5.4 Hz, - 2 ), 3.72 (t, 2H, J = 5.4 Hz, 2 - ), 3.76 (s, 2H, -C=), 4.55 (s, 2H, Ar- ), (m, 4H, Ar-H); 13 C NM (100 MHz, DM-d 6 ): δ 36.7 (C-5), 45.5 ( 2 - ), 46.8 ( - 2 ), 57.5 (C- 4), 59.2 ( -C=), 62.6 (Ar- ), (Ar-C), (Ar-C), (Ar-C), (Ar-C), (C-2). Anal. Calcd for C 13 H 16 ClN 4 3 : C, 40.88; H, 4.22; N, Found: C, 40.95; H, 4.26; N, 3.71%. Method B General method for preparation of 2-(benzylsulfonylethylsulfonylmethyl)oxazolines 10/2-(benzylsulfonylethylsulfonylmethyl)thiazolines 12 by using samarium(iii) chloride To a flask charged with anhydrous samarium (III) chloride ( mol) and dry toluene (10 ml), 2- aminoethanol (0.002 mol) / 2-aminoethanethiol (0.002 mol) was added followed by n-butyllithium ( mol) at 0 C. The reaction mixture was stirred at 0 C for 30 min and heated to reflux. Then, benzylsulfonylethylsulfonylacetic acid methyl ester 7 (0.001 mol) was added to the contents and reflux continued for an additional period of 6-9 hr. The suspension was cooled to T and filtered. The filtrate was extracted with chloroform, washed with water followed by brine solution. The solvent was removed in vacuo. The solid obtained was purified by column chromatography (silica gel, ethyl acetate:hexane-1:3), to give 10a in 72% yield / 10b in 71% yield / 10c in 73% yield / 12a in 69% yield / 12b in 71% yield / 12c in 68% yield as white solid. Method C General method for preparation of 2-(benzylsulfonylethylsulfonylmethyl)oxazolines 10/2-(benzylsulfonylethylsulfonylmethyl)thiazolines 12 under microwave irradiation 2-(Benzylsulfonylethylsulfonylmethyl)oxazoline, 10 The compound benzylsulfonylethylsulfonylacetic acid 6 (0.01 mol) and 2-aminoethanol (0.01 mol) were placed in a Pyrex flask in such a way as to occupy only 10% of the overall volume. The mixture was irradiated using the multimode at 540 W for 3 min and monitored by TLC. When all the starting material had disappeared, the irradiation was terminated and the mixture was brought to T. To this dichloromethane was added and filtered. The resultant compound obtained by evaporation of the solvent was purified by column chromatography (silica gel, ethyl acetate:hexane 1:2.5) to give 10a in 92% yield / 10b in 91% yield / 10c in 90% yield as white solid (Table I). 2-(Benzylsulfonylethylsulfonylmethyl)thiazoline, 12 The compound benzylsulfonylethylsulfonylacetic acid 6 (0.01 mol) and 2-aminoethanethiol (0.01 mol) were placed in a Pyrex flask in such a way as to occupy only 10% of the overall volume. The mixture was irradiated at 560 W for 4 min and monitored by TLC. When all the starting material had disappeared, the irradiation was terminated and the mixture was allowed to cool to T. The dichloromethane was added to the resulting mixture and filtered. The compound obtained after evaporation of the solvent was purified by column chromatography (silica gel, ethyl acetate:hexane 1:2.5) to give 12a in 93% yield / 12b in 89% yield / 12c in 90% yield as white solid (Table I).

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