Antituberculous compounds. V. 2-Sulfanilamido-5-alkyl-1,3,4-oxadiazoles and -thiadiazoles and related isothiosemicarbazones and isothioureas was written by Brooks, J. D.;Charlton, P. T.;Macey, P. E.;Peak, D. A.;Short, W. F.. And the article was included in Journal of the Chemical Society in 1950.Application In Synthesis of 6-Butoxybenzo[d]thiazol-2-amine The following contents are mentioned in the article:
This work arose out of the observation that 2-sulfanilamido-5-methyl-1,3,4-oxadiazole (I), although virtually inactive against organisms normally sensitive to sulfonamides, exhibited a highly sp. activity in vitro against Mycobacterium tuberculosis. N4-Acyl derivatives of I were prepared from the acid anhydride in C6H6 (hexanoyl, m. 203°) or with the acid chloride in C5H5N (dodecanoyl, m. 124°; stearoyl, m. 128-9°). I(2.5g.)in 15 cc. H2O and 4cc. concentrated HCl, treated with 3.3 g. iodine monochloride in 3 cc. concentrated HCl, gives 3 g. 2-(3,5-diiodosulfanilamido)-5-methyl-1,3,4-oxadiazole, m. 228-9°. 1-Acylthiosemicarbazones were prepared with the appropriate acid anhydride at 80° and finally at 110-20°; 10 g. of the crude product and 3 mols. PbO, heated 15-30 hrs. in 150-200 cc. EtOH, give the 5-alkyl derivatives of 2-amino-1,3,4-oxadiazole: 5-Am, m. 151° (N-sulfanilyl derivative, m. 148-9°; N4-Ac derivative, m. 186°); 5-hendecyl, m. 150-1° (N-sulfanilyl derivative, m. 105-7°); 5-heptadecyl, m. 143° (N-sulfanilyl derivative, m. 91-3°). 2-(p-Tolylsulfonamido)-5-methyl-1,3,4-oxadiazole, m. 152°. 1-Hexanoylthiosemicarbazide (22 g.) and 30 g. PhSO3H, heated 15 min. on the steam bath and the aqueous solution basified with NH4OH, give 17 g. 2-amino-5-amyl-1,3,4-thiadiazole, m. 195°; 2-sulfanilamido analog, m. 182° (N4-Ac derivative, m. 201-2°). In view of the unfavorable in vivo properties of the above compounds, a series of 3-alkylisothiosemicarbazones (II) and 2-alkylisothioureas was prepared p-BuOC6H4NCS (III) (4.25 g.) in 6 cc. absolute EtOH, treated with 1.2 cc. 90% N2H4.H2O in 1 cc. EtOH and the crude product refluxed 3 hrs. with 2.2 g. BzH in 60 cc. EtOH, gives 4.5 g. benzaldehyde 4-p-butoxyphenylthiosemicarbazone, pale yellow, m. 164-5°. The II were prepared from the corresponding thiosemicarbazones by alkylation with EtONa and the appropriate alkyl halide in EtOH. Acetone 3-ethylisothiosemicarbazone (IV) HCl salt m. 153-4°; 3.2 g. IV and 2.1 g. NaHCO3 in 25 cc. 50% EtOH, treated with 5.13 g. p-AcNHC6H4SO2Cl, give 0.67 g. of the 4-(N-acetylsulfanilyl) derivative (V), m. 183-4°; 0.17 g. V and 1 cc. 2.5 N NaOH, heated 1 hr. at 100°, give 0.14 g. of the 4-sulfanilyl derivative, m. 186-7°. Benzaldehyde 3-butylisothiosemicarbazone HCl salt, m. 185-6°; 3-octyl homolog HCl salt, m. 176°; 3-hexadecyl homolog HCl salt, m. 162-3°; 3-(2-diethylaminoethyl) analog di-HCl salt, m. 192°. Benzaldehyde 4-phenyl-3-ethylisothiosemicarbazone (VA), pale yellow m. 78°; the 3-(2-diethylaminoethyl) analog forms a reineckate, m., 166-7° (decomposition). 4-(p-Butoxyphenyl) analog of VA, m. 90°. p-1-Pyrrolidylbenzaldehyde 3-ethylisothiosemicarbazone HCl salt, reddish brown, m. 245° (decomposition). p-Dimethylaminobenzaldehyde 3-ethylisothiosemicarbazone di-HCl salt, yellow, m. 219-20° (decomposition); boiling EtOH gives the mono-HCl salt, red, m. 230-2°. 2-Nitrobenzaldehyde analog HCl salt m. 169.5-70.5°. The S-alkylisothioureas were prepared from the appropriate thiourea and alkyl halides in boiling EtOH: N-phenyl-S-ethyl (VI) (picrate, yellow, m. 199.5°); S-Bu homolog (picrate, yellow, m. 144°); S-octyl homolog (picrate, yellow, m. 130.5°). N-p-Butoxyphenyl analog of VI (picrate, yellow, m. 162-3°); S-Bu homolog, (HI salt, m. 109-10°); S-octyl homolog (HBr salt, m. 96-6.5°). The activities of the thiadiazoles and the thiosemicarbazones are entirely unrelated. The low activity of the S-alkylisothioureas in the serum precluded in vivo activity. 2-Mercaptobenzimidazole and EtI, refluxed 2 hrs. in EtOH, give the 2-ethylmercapto analog m. 173.5-4.5°. p-BuOC6H4NH2 (8.25 g.) and 9.5 g. NH4NCS in 50 cc. 95% AcOH, treated with 10 g. Br in 13 cc. AcOH and kept overnight, give 2.2 g. 2-amino-6-butoxybenzothiazole, m. 119°. 2-Chloro-6-nitrobenzothiazole (10 g.) in 250 cc. BuOH, refluxed 20 hrs. with 1.07 g. Na in 50 cc. BuOH, give 4.15 g. 6-nitro-2-butoxybenzothiazole (VII), m. 60°; 10 g. VII, added in portions to 32 g. SnCl2.2H2O in 40 cc. concentrated HCl at 70-80° and finally refluxed 30 min., gives 2.5 g. x-chloro-6-amino-2-butoxybenzothiazole-2HCl, m. 268° (decomposition). In the preparation of 2-mercapto-4-phenyl-6-methylpyrimidine (VIII), the fraction insoluble in EtOH, dilute HCl, or NaOH is bis(4-phenyl-6-methyl-2-pyrimidyl) disulfide, yellow, m. 185.5-6°; it results on oxidation of VIII in dilute NaOH with aqueous iodine. The appropriate S-alkylisothiourea-HX in 1 equivalent 2.5 N NaOH, treated with 1 mol. crude Et sodioformylpropionate, gives a 4-hydroxy-2-alkylmercapto-5-methylpyrimidine; with PCl5 and POCl3 (refluxed 45 min.) they give the 4-Cl compounds; these give the 4-NH2 compounds when heated 6-8 hrs. with 8-10 parts (by weight) 10% EtOH-NH3 at 135-50°. The following pyrimidines are reported: 2-methylmercapto-4-phenyl-6-methyl, b1 154-60°; 4-hydroxy-2-butylmercapto-5-methyl, m. 105-6°; 2-octylmercapto analog, m. 88-9°; 4-chloro-2-methylmercapto-6-methyl, b15 132°, m. 20-3°; 4-chloro-2-butylmercapto-5-methyl, b1 124-6°; octylmercapto homolog, b2 144-8°; 4-amino-2-methylmercapto-5-methyl, m. 130-1°; butylmercapto homolog, m. 85-6°; octylmercapto homolog, m. 85-6°. In no case were the compounds active at a dilution greater than 1:1000 in the presence of serum. This study involved multiple reactions and reactants, such as 6-Butoxybenzo[d]thiazol-2-amine (cas: 14372-65-7Application In Synthesis of 6-Butoxybenzo[d]thiazol-2-amine).
6-Butoxybenzo[d]thiazol-2-amine (cas: 14372-65-7) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1).Various laboratory methods exist for the organic synthesis of thiazoles. For example, 2,4-dimethylthiazole is synthesized from thioacetamide and chloroacetone.Application In Synthesis of 6-Butoxybenzo[d]thiazol-2-amine
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica