THE SYNTHESIS OF POTENTIAL ANTIMALARIALS. SOME SUBSTITUTED N-PHENYLSULFONAMIDES¹

Abstract

Drugs of the sulfonamide type have recently been extensively investigated as antimalarials. As part of this general program the compounds in Table I were prepared.3As intermediates, several unreported aniline derivatives were required and their preparation is also described.These compounds were prepared by coupling an appropriate sulfonyl chloride with the required aniline derivative and hydrolyzing or reducing the product to the final compound. The method of coupling and hydrolysis employed was essentially that of Long and Burger (1), but it was found that variations in the experimental details were of great importance in obtaining satisfactory yields of the products.

Amide as Nitrogen Source： Amination and Mechanism

“…163～166 ℃ (lit. [12] 163～166 2962,2889,2853,1593,1565,1481,1436,1376,1312,1243,1160,1121,1070 (KBr) v: 3088, 3060, 2912(KBr) v: 3088, 3060, , 2854(KBr) v: 3088, 3060, , 1623(KBr) v: 3088, 3060, , 1572(KBr) v: 3088, 3060, , 1523(KBr) v: 3088, 3060, , 1481(KBr) v: 3088, 3060, , 1446(KBr) v: 3088, 3060, , 1342(KBr) v: 3088, 3060, , 1224(KBr) v: 3088, 3060, , 1190 2-吗啡啉基苯并噻唑(3l) [20] : 1 H NMR (400 MHz, DMSO-d 6 ) δ: 7.42～7.40 (m, 1H), 7.31～7.29 (m, 1H), 7.18～7.14 (m, 1H), 7.05～7.01 (m, 1H), 3.73～3.70 (m, 4H), 3.59～3.57 (m, 4H); 13 C NMR (100 MHz, CDCl 3 ) δ: 168. 9, 152.4, 130.5, 126.0, 121.6, 120.7, 119.2, 77.3, 77.0, 76.7, 66.2, 48.4; MS (ESI) m/z (%): 221.1 (M ＋ , 100).…”

N2-(2,6-Dibromo-4-nitrophenyl)-N1,N1-diethyl-2-(triisopropylsilyl)ethanamidine

“…For the preparation of compounds (III) and (IV), 3,5-dibromo-4iodonitrobenzene, (I), was prepared from 2,6-dibromo-4-nitroaniline, (II) (Senear et al, 1946). (I) (1.50 g, 3.69 mmol), CuCl (54.5 mg, 0.55 mmol) and [Pd(PPh 3 ) 2 Cl 2 ] (381 mg, 0.54 mmol) were dissolved in Et 3 N (50 ml) under argon.…”

“…During these studies, we have developed routes to a number of alkyne-containing building blocks containing mixed halo substituents to facilitate preferential alkyne-coupling at specific sites under Sonogashira conditions (Sonogashira et al, 1975;Sonogashira, 2002). A key building block is (I) (see scheme), which is prepared from 2,6-dibromo-4-nitroaniline, (II) (Senear et al 1946). In the reaction of a crude sample of (I) containing (II) with i Pr 3 SiCCH under Sonogashira conditions, we isolated a single crystal of (IV) in addition to the expected alkyne (III).…”

Structure of 2,6-dibromo-N-methyl-4-nitroaniline (DBNMNA); a new electro-optic organic crystal

“…DBNMNA (m.p. 389-390 K) was prepared by the reaction of bromine with N,N-dimethyl-4-nitroaniline in methanol at reflux (Tsuda, 1969;* Senear, Rapport, Mead, Maynard & Koepfli, 1946;Blanksma, 1902). Powder X-ray diffraction patterns, obtained using a Philips APD-3600 diffractometer in parafocus geometry using Cu Ka radiation, showed that crystals obtained from acetonitrile, ethanol and methylene chloride all have the same structure.…”