3-Substituted thiophenes. III. Antihistaminics of the N-3-thenylethylenediamine series was written by Campaigne, E.;LeSuer, William M.. And the article was included in Journal of the American Chemical Society in 1949.Reference of 36157-41-2 This article mentions the following:
2-Chloro-3-methylthiophene (I) (66 g.) in 150 ml. CCl4, treated with 88.5 g. (CH2CO)2NBr (II) and 1 g. Bz2O2 and refluxed 8 hrs., gives 75% 2-chloro-3-thenyl bromide, b1 88°, n22D 1.6119; the hexamethylenetetramine salt (m. 165°, 84%) on distillation with steam yields 25% 2-chloro-3-thenaldehyde, b1-2 100-2°, m. 25°, n20D 1.5908 (2,4-dinitrophenylhydrazone, orange, m. 214°); oxidation with Ag2O in ether gives 75% 2-chloro-3-thenoic acid, m. 163°. 2-Bromo-3-methylthiophene with II yields 65% 2-bromo-3-thenyl bromide, b7 113°, n20D 1.6241; the hexamethylenetetramine salt (m. 171-2°, 75%) on steam distillation yields 15% 2-bromo-3-thenaldehyde, m. 34° (2,4-dinitrophenylhydrazone, orange, m. 230.5°); 2-bromo-3-thenoic acid m. 178-9°, 78%. 3-Methylthiophene (296 g.), added (3 hrs.) to 810 g. SO2Cl2 (total refluxing 5 hrs.), gives 8% I and 63% 2,5-di-Cl derivative (III), b11 65°, n20D 1.5560. III and II give 69% 2,5-dichloro-3-thenyl bromide, b4 104.5-6°, n20D 1.6177; the hexamethylenetetramine salt [m. 178-80° (decomposition), 90%] yields a crude aldehyde, which gives 11.4% 2,5-dichloro-3-thenoic acid, m. 146.5-7.5°. NaNH2 (3.12 g.) in 50 ml. PhMe, treated dropwise with 12 g. 2-(dimethylaminoethylamino)pyridine, refluxed 2 hrs., treated dropwise at 50° with 21 g. 3-thenyl bromide, refluxed 2 hrs., poured into 150 ml. H2O, the PhMe layer extracted with 5% HCl, and the HCl layer saturated with K2CO3 and extracted with ether, gives 31.4% 2-[3-thenyl-(2-dimethylaminoethyl)amino]pyridine (IV), yellow, m. 169-72°, n20D 1.5915. (Halo-3-thenyl) derivatives of IV: 2-Cl b1 156-8°, n20D 1.5950, 28%; 2-Br b1 177-9°, n20D 1.6590, 20%; 2,5-di-Cl b1 179-81°, n20D 1.5968, 38%. IV (106 g.) in 500 ml. iso-PrOH and 34 ml. concentrated HCl give 86% of the HCl salt, m. 169.5-70°. In the experiment, the researchers used many compounds, for example, 2,5-Dichlorothiophene-3-carboxylic acid (cas: 36157-41-2Reference of 36157-41-2).
2,5-Dichlorothiophene-3-carboxylic acid (cas: 36157-41-2) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Reference of 36157-41-2
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics