A one-pot synthesis of methyl 6-chlorosulfonyl-3-methyl-1,2-benzoxathiin-8-carboxylate 2,2- dioxide (9), characterized as its 6-(4-methylpiperazin-1-yl)sulfonyl derivative 10, is achieved via direct reaction of methyl 3-allylsalicylate (1) with chlorosulfonic acid at −7°C. The latter reagent converts methyl 2-methyl-2,3-dihydrobenzofuran-7-carboxylate (3) into the respective 5-chlorosulfonyl derivative 7 (identified as its 5-(4-methylpiperazin-1-yl)sulfonyl derivative 8), while contrary to literature reports, the aromatic δ -sultones 9, 10 (anticipated to be produced from 3) were not detected.
A series of N-(2-chloro-7-cyclopropyl-4,7-dihydro-4-oxothieno[2,3-b]pyridine-5-carbonyl)-L-α-amino esters (5 ) have been prepared via the respective thieno[2,3-b]pyridinyl-5-carbonyl chloride (4). The CD spectra of the L-aliphatic (5a -d ) and L-aromatic (5e-g) a-amino acid derivatives display, in organic solvents, sign inversion of the measured Cotton effect (CE) bands. This chiroptical behaviour is probably associated with differences in conformational isomerism of either set. MS and NMR spectral data of the title compounds are presented.
X-ray crystal structure data for the substituted 5-(2,3-dihydro-7-benzofuryl)-2-methylpyrazolo[ 4,3-d]pyrimidin-7-one (3) reveal that the two bicyclic heteroaryl systems show no coplanarity along their joint C (5) - C (11) axis with an interplanar angle of 9.6°. Nonetheless, the spatial interatomic distance for O(17)-N(6), determined as 2.73 A, allows the formation of a relatively weak intramolecular hydrogen bond between the pyrimidinone N(6)-H and the O(17) lone pair of the dihydrobenzofuryl moiety.
Cyclocondensation reaction of ethyl 7,8-diamino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline- 3-carboxylate (2) or the -3-carboxylic acid 3 with sym-1,2- diketones produced the corresponding ethyl 2,3-disubstituted pyrido[2,3- f ]quinoxaline-8-carboxylates (4a - h) or the -8-carboxylic acids 5a - h, respectively. The structures for these new heterocycles are supported by analytical and spectral (IR, MS, NMR) data. Compounds 5a - c, g, h exhibit moderate activity against an assortment of bacterial species.
γ -Aminobutyric acid (GABA) adds onto nitrile imine 1,3-dipolar species (generated in situ from their N-arylhydrazonoyl chloride precursors 1a-c ) to deliver the corresponding acyclic amidrazone adducts 10a-c. In the presence of 1,1’-carbonyldiimidazole, the latter adducts undergo cyclocondensation involving the activated carboxyl and the amidrazone-CH2NH groups to afford the respective N-[1-(arylhydrazono)-2-oxopropan-1-yl] pyrrolidin-2-ones (11a-c). The constitution of 10 and 11 is evidenced from analytical and spectral (IR , MS and NMR) data.
X-ray crystal structure data for the title compound dihydrobenzofuryl-pyrazolo[4,3-d]pyrimidin- 7-one (2) reveal that the two bicyclic heteroaryl systems are virtually coplanar along their joint C (5)-C(11) axis with an interplanar angle of 1.13°. This planar conformation is held by an intramolecular hydrogen bond between the pyrimidinone N(6)-H and the O(17) lone pair of the dihydrobenzofuryl moiety. The spatial interatomic distance for O(17)-N(6), determined as 2.04 Å, favours this H-bridge.
Direct interaction of salicylaldehyde oxyanion with ethyl 7-chloro-8-nitro-4-oxoquinoline-3- carboxylate (2) delivered the respective 7-(2-formyl-phenoxy)-8-nitro-4-oxoquinoline-3-carboxylic ester 3. Reductive cyclization of 3 furnished the corresponding 4-oxo-[1,4]benzoxazepino[2,3- h]quinoline-3-carboxylic ester 5. Acid-catalyzed hydrolysis of the esters 3/5 produced the respective acids 4/6. Structural assignments for the new compounds 3 - 6 are supported by microanalytical and spectral (IR, HRMS, NMR) data and confirmed by X-ray structure determination for compound 5. Interestingly, compound 6 exhibited good antifungal activity against C. albicans.
A series of 3-(alkylthio)-6-chlorothieno[2,3-e][1,4,2]dithiazine 1,1-dioxides (7a - e) were prepared via interaction of deprotonated 2,5-dichlorothiophene-3-sulfonamide with carbon disulfide under reflux, followed by alkylation with alkyl halides. Employment of dimethyl sulfate afforded the isomeric 2-methyl-3-thione derivative 8 together with the expected 3-(methylthio) derivative 7a in a molar ratio of 1 : 4. Treatment of 7a or 10 with ethylamine, aniline or p-chloroaniline produced the corresponding N-ethyl- (or N-phenyl)-6-chlorothieno[2,3-e][1,4,2]dithiazine-3-amine 1,1-dioxides 3a - c. Likewise, interaction of 7a with methylhydrazine (or phenylhydrazine) gave the respective 3-(1-methylhydrazinyl or 2-phenylhydrazinyl) 1,1-dioxides 9a, b. Desulfonation of 6-chloro-3-(methylthio)thieno[ 2,3-e][1,4,2]dithiazine 1,1-dioxide (7a) with sulfuryl chloride produced 3,6-dichlorothieno[2,3- e][1,4,2]dithiazine 1,1-dioxide (10). The latter compound was used as a substrate for the preparation of N-alkyl- (or aryl)-6-chlorothieno[2,3-e][1,4,2]dithiazin-3-amine 1,1-dioxides 3a - c representing a new approach for the synthesis of similar derivatives. Compounds 7a - e showed modest to low antibacterial activity against E. coli and S. aureus.
Methyl 3-aminothiophene-2-carboxylate reacts readily, in the presence of triethylamine, with hydrazonoyl chlorides (7a - c) to afford good yields of the corresponding N-arylamidrazones (8a - c). The latter acyclic adducts undergo, in the presence of t-BuOK/t-BuOH, cyclocondensation accompanied by elimination of the acetyl group present in 8, to deliver the respective thieno-1,3,4-triazepin- 5-ones 10a - c.