2-(CHLOROMETHYL)-1,3-BENZOTHIAZOLE

Carbon tetrachloride (15. 0ml, 155mmol) is added to a stirred solution of benzothiazolyl-2-methanol (2. 50g, 15. 1mmol), triphenylphosphine (4.89g, 18. 6mmol), and anhydrous toluene (50ml). The reaction is heated to reflux under nitrogen for 5h. It is then concentrated on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 100percent dichloromethane to yield (2. 36g, 85percent) of 2-chloromethyl-benzothiazole : mass spectrum (ion spray): m/z = 183.9 (M+1) : lH NMR (CDC13) : 8=8. 04-8.01 (1H, m), 7.91-7. 89 (1H, m), 7.53-7. 49 (1H, m), 7.44-7. 40 (1H, m), 4.95 (2H, s).To a solution of 2-aminobenzenethiol (1 g, 7.93 mmol) in acetic acid (15 mL), and 2-chloroacetyl chloride (1.35 g, 1.19 mmol) was added dropwise.The reaction mixture was irradiated in a microwave oven (Ethos start) for 10 min at a power of 500 W.After cooling, the mixture was poured onto crushed ice (100 mL) and basified with 5 mol/L NaOH.The solution was extracted with chloroform (3 50 mL). The combined organic layers were dried overMgSO4 and concentrated under vacuum. Purification of the residue by column chromatography onsilica gel (petroleum ether/acetone, 10:1 v:v) gave compound 4 as a yellow solid (1.90 g, 86.8percent) [27].m.p., 89–90 °C; MS (+ESI) m/z 184.02 [M + H]+.General procedure: A solution of 2-aminothiophenol 28 (5 g, 39.93 mmol) in toluene (50 ml) and 5-chloropentanoyl chloride (18) (6.81 g, 44 mmol) was added dropwise with cotinuous stirring over a 15 min period resulting in the formation of an off-white precipitate. The mixture was allowed to continue stirring at rt overnight and then partitioned between HThe mixture of 2-aminothiophenol (0.85 ml, 8 mmol) 2-chloroacetyl chloride (0.95 ml, 12 mmol) in acetic acid (15 ml) was irradiated in a microwave reactor for 10 min at 120 oC. After cooling, the mixture was poured onto crushed ice (100 ml), basified with 5N NaOH. The precipitate formed was filtered by suction filtration, washed with water and dried. (Yield, 74percent)A solution of 2-aminothiophenol (2.0 g, 16.0 mmol)in toluene (20 mL) and 2-chloroacetyl chloride was addeddropwise with continuous stirring over 15 min. The mixture was allowed tocontinue stirring at rt. The mixture was portioned between water and EA. Thecrude was purified by silica gel (PE/EA = 20/1) to give the product ascolorless oil. (1.9 g, 65percent yield)This compound was synthesized according to the previously described procedure.5 To asolution of 2-amino-thiophenol (2.0 g, 18.50 mmol, 1.0 equiv.) in xylene (20 mL), chloroacetyl chloride (2.25 mL, 27.80 mmol, 1.5 equiv.) was added under argon, followed by drop-wise addition of Et3N (7.70 mL, 55.50 mmol, 3.0 equiv.). The reaction mixture was initially stirred for 1 h at room temperature, and then overnight at 120 °C. A saturated aqueous solution of NH4Cl (100 mL) was added to the reaction mixture, which was then transferred to a separating funnel. The mixture was extracted with EtOAc (3× 50 mL), and the combined organic phases were washed with saturated brine solution (100 mL), dried over Na2SO4, and evaporated under reduced pressure. The crude product was purified by short flash column chromatography using EtOAc/n-hex = 1/4 as eluent, to obtain 1.52 g of the compound. Yield: 45percent; pale brown crystals, mp 120–124 °C (lit.5 colorless oil; mp 34 °C6);1H NMR (400 MHz, CDCl3): δ 4.95 (s, 2H, CH2), 7.43 (ddd, J = 8.0, 7.2, 1.2 Hz, 1H, Ar-H), 7.51 (ddd, J = 8.0, 7.2, 1.2 Hz, 1H, Ar-H), 7.90 (ddd, J = 8.0, 1.2, 0.8 Hz, 1H, Ar-H), 8.03(ddd, J = 8.0, 1.2, 0.8 Hz, 1H, Ar-H).General procedure: Synthesis of benzothiazole derivatives(3 a-p) was carriedout according to the procedure reported by Kenny andMashelkar (2006). Different benzaldehydes (2, 5.5 mmol)and 2-aminothiophenol (1, 5 mmol) were taken in a roundbottomflask containing 7 ml of acetic acid. The reactionmixture was refluxed for 5–6 h (Scheme 1). The reactionwas monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature anddecomposed over ice–water mixture. The solid thusobtained was collected by filtration. The crude product waspurified either by crystallization using ethanol or by columnchromatography using hexane: ethyl acetate as solvent.All the synthesized compounds were characterized byspectroscopic methods.

Molecular Weight:183.66
XLogP3:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:182.9909481
Monoisotopic Mass:182.9909481
Topological Polar Surface Area:41.1
Heavy Atom Count:11
Complexity:142
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes