Jatinder P. Bassin

CHLOROSULFONATION OF SOME POLYNUCLEAR HETEROCYCLIC COMPOUNDS

Abstract Dibenzofuran (1), dibenzothiophen (20) and the 5,5-dioxide (29), carbazole (43) and fluorene (50) have been reacted with chlorosulfonic acid. The resultant sulfonyl chlorides (2, 12, 18, 21, 23, 27, 30, 37, 44, 46 and 51) were condensed with amines and hydrazine to afford 32 derivatives for biological screening. The orientation of chlorosulfonation has been determined by NMR spectral analysis and is compared with the chlorosulfonation of the analogous acyclic compounds. Selected compounds were tested as potential pest control agents.

CHLOROSULFONATION OF N-PHENYLMORPHOLINE, BENZOTHIAZOLE, 2-METHYL BENZOTHIAZOLE AND TRIPHENYLOXAZOLE

Abstract N-Phenylmorpholine (1) reacted with chlorosulfonic acid to give the p-sulfonyl chloride (2), which was characterized as the sulfonamides (3–5). Benzothiazole (6) was converted into the sulfonyl chloride (7) by sequential treatment with hot chlorosulfonic acid and thionyl chloride. Reaction of (7) with amines afforded the derivatives (8–10); NMR spectral analysis of the dimethylamide (8) indicated that it was a mixture of the 4- and 7-isomers. Chlorosulfonation of 2-methylbenzothiazole (11) was achieved by heating with chlorosulfonic acid with or without thionyl chloride. The chloride (12) was converted into amides (13–19). Study of the NMR spectra indicated that mixtures of the 5- and 6-isomers were formed. 2,4,5-Triphenyloxazole (20) reacted with chlorosulfonic acid to give either the mono-(21), bis (23) or bis-tris sulfonylchlorides (23, 34); these were converted into 14 sulfonamides. 2-(p-Nitrophenyl)-4,5-diphenyloxazole (41) reacted with hot chlorosulfonic acid to give the bis-sulfonyl chlori...

CYCLISATION OF DIARYL COMPOUNDS WITH CHLOROSULFONIC ACID

Abstract Biphenyl(1) and other compounds of type PhXPh (X = O(19); S(30); NH(33); CH2(40); (CH2)2(41); (CH2)3(51); C(CH3)2(55) were reacted with chlorosulfonic acid. Under forcing conditions (100–150°C), compounds 1, 19, 33, 40, 41, and 55 afforded the cyclic sulfones (2,26,27,39, 43, and 63). Cyclisation occurred most readily with diphenylethane (41) to give the 7-membered sulfone (46). On the other hand, diphenylsulfide (30) and diphenylpropane (51) failed to give cyclic products, while 2,2-diphenylpropane (55) afforded only a low yield of the cyclic compound (63) among a mixture of uncyclised products (57, 61, 62). With chlorosulfonic acid under milder conditions, the substrates afforded mono-, di, tri- and tetra-sulfonyl chlorides which have been converted into 32 sulfonamides for screening as candidate medicinals and pesticides. The spectroscopic properties of selected compounds are briefly discussed with special reference to the orientation of sulfonation.

Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives

A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1–9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10–18. These were converted to the dibromo compounds 19–27 through reaction with bromine in glacial acetic acid. Compounds 19–27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28–72. Compounds 28–72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-positive bacteria Bacillus subtilis and Staphylococcous aureus. The range of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was 25–600 µg/mL, though some of the MIC and MBC concentrations were high, indicating weak activity. Structure activity relationship studies revealed that the compounds with a hydrogen atom or an ethyl group on the nitrogen of the thiazine ring exerted antibacterial activity against Gram-positive bacteria. The results also showed that the compounds where the benzene ring of the benzoyl moiety contained a methyl group or a chlorine or bromine atom in the para position showed higher antimicrobial activity. Similar influences were identified where either a bromine or chlorine atom was in the meta position.

CHLOROSULFONATION OF αβ-UNSATURATED ARYLIDENE KETONES

Abstract 2-Thienylideneacetone (4), and the benzylidene derivatives of ethyl methyl ketone (19) and diethyl ketone (20) were reacted with excess chlorosulfonic acid to give the thienylidene 5,β-disulfonyl chloride (5) and the styrene disulfonyl chlorides (21 and 22). These were characterized by preparation of the sulfonamides (6-9, 23 and 24) required for screening as pest control agents. Benzylidene acetone (1) was condensed with aryl aldehydes to give the corresponding 1,5-diaryl-1,4-dien-3-ones (25-28), but the condensation failed with p-anisaldehyde and o-vanillin. Attempted chlorosulfonation of compounds (25 and 28) was unsuccessful and the products could not be characterised as sulfonamide derivatives. The 1H NMR spectra of selected compounds are briefly discussed.

CHLOROSULFONATION OF 5,5-DIPHENYLHYDANTOIN AND 5-ARYLIDENEBARBITURIC ACIDS

Abstract 5,5-Diphenylhydantoin (1) by heating with chlorosulfonic acid gave a bis-sulfonyl chloride (2) in which the orientation of sulfonation is apparently meta/para. The chloride (2) was converted into 8 sulfonamides (3–10). Barbituric acid has been condensed with aromatic aldehydes to yield 18 5-arylidene derivatives (11–28). The reaction of chlorosulfonic acid with 5-benzylidenebarbituric acid (11) is discussed together with the subsequent reaction of the sulfonyl chloride with amines. The chlorosulfonation of other arylidenebarbituric acids (12-14, 22, 23, 26 and 28) has also been examined.

Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives

A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The 1H- and 13C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra.

(Z)-3-Chloro-methyl-idene-5,6-dimeth-oxy-2-methyl-2,3-dihydro-1,2-benzothia-zole 1,1-dioxide.

The title compound, C11H12ClNO4S, adopts a Z configuration about the C=C double bond. The benzisothiazole system is essentially planar [maximum deviation of 0.235 (2) Å for the S atom]. In the crystal, the molecules stack parallel to each other in the b-axis direction, with interplanar spacings for the benzene and thiazole rings ranging from 3.402 (2) to 3.702 (2) Å.

Synthesis and antibacterial activity of benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide derivatives

Using a routine procedure, a number of derivatives of the benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide ring system have been synthesized from readily available starting materials. A series of chalcones were synthesized, which were subsequently reacted with chlorosulfonic acid to generate chalcone sulfonyl chlorides. The chalcone sulfonyl chlorides were then treated with bromine to generate dibromo chalcone sulfonyl chlorides. These were subsequently reacted with 1,2-diaminopropane and 2-methyl-1,2-diaminopropane in boiling ethanol resulting in compounds 2–10 and 11–19 respectively, in 12–80% yields. The products were characterized by spectral analysis and the definitive structure of compound 11 was determined by X-ray crystallography. The synthesized compounds were screened for potential antibacterial properties against Bacillus subtilis, Escherichia coli, Proteus vulgaris and Staphylococcus aureus.

Racemic 9,10-dimeth­oxy-3-methyl-6-phenyl-7,7a-dihydro­benzo[b]benzo[4,5]isothia­zolo[2,3-d][1,4]diazepine 12,12-dioxide

There are two molecules in the asymmetric unit of the title compound, C24H22N2O4S. The conformation of the seven-membered ring is twisted boat for both molecules. The molecule is chiral, but crystal symmetry generates a recemate. The crystal packing is stabilized by weak intermolecular C—H⋯O hydrogen bonds.