Reactions of 1,2,4-triazole derivatives with a “model” thiirane

Reactions of 3-mono- and 3,5-disubstituted 1,2,4-triazoles with a “model” thiirane, 8-bromo-1,3-dimethyl-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-purine-2,6-diones proceed at the positions N¹ and N² of the triazole ring and yield 7-(5-R-3-R′-1,2,4-triazol-1-yl)methyl- and/or 7-(5-R′-3-R-1,2,4-triazol-1-yl)methyl-1,3-dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]-purine-2,4-(1H,3H)-diones. 3-Methylsulfonyl-1,2,4-triazole reacted regiospecifically at the position N¹ forming 1,3-dimethyl-7-[(3-methyl-sulfonyl-1,2,4-triazole-1-yl)-methyl]-6,7-dihydro[1,3]thiazolo-[2,3-f]purine-2,4(1H,3H)-dione.     

Synthesis and microbial screening of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives

The present investigation describe the synthesis of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Quinolin-8-ol was transformed by five step synthetic procedures into 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one. Subsequently, 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one condensed with 1,3-Diphenyl-1H-pyrazole-4-carbothioic acid amide in the presence of acetonitrile to afford 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Synthesized compounds were screened for their antimicrobial activity against gram-positive and gram-negative bacteria. Most of the synthesized compounds are found to be active against tested bacterial strains and fungal strain.     

Synthesis of 4-thia analogues of isoquinoline alkaloids

Summary (±)-4-Thiacarnegin (3) was synthesized by reaction of 6,7-dimethoxy-3-methyl-2H-1,3-benzothiazinium iodide (2) with methyl magnesium iodide, thereby opening a new synthetic route to 4-substituted dihydro-2H-1,3-benzothiazines. Compound3 was also obtained by reduction of 6,7-dimethoxy-3,4-dimethyl-2H-1,3-benzothiazinium iodide (5). In a similar way, reduction of the quaternary salts9 a–c afforded the (±)-4-thia analogues of cryptostilin-I, -II and -III (10 a–c). The isomers of the former compounds (12 a–c) were also synthesized by reduction of the 4H-1,3-benzothiazinium salts11 a–c.

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Synthese von 4-Thiaanalogen von Alkaloiden mit Isochinolingerüst

Zusammenfassung Aus 6,7-Dimethoxy-3-methyl-2H-1,3-benzothiaziniumjodid (2) wurde mit Methylmagnesiumjodid (±)-Thiacarnegin (3) dargestellt. Diese Reaktion bietet ein neues Verfahren für die Synthese von 4-substituierten Dihydro-2H-1,3-benzothiazinen.3 wurde auch durch Reduktion von 6,7-Dimethoxy-3,4-dimethyl-2H-1,3-benzothiaziniumjodid (5) erhalten. Die Reduktion der quartären Ammoniumsalze9 a–c ergab ebenfalls die Cryptostillin I-, II-, III-(±)-4-thiaanalogen Verbindungen (10 a–c). Reduktion der 4H-1,3-Benzothiazinium-Salze11 a–c lieferte die entsprechenden Isomeren12 a–c der obengenannten Verbindungen.

     

Synthesis and Structure of Quaternary Salts Derived from 2-Anilino- and 2-Benzylamino-5,6-dihydro-4H-1,3-thiazine

Substituted phenacyl bromides react with 2-anilino-5,6-dihydro-4H-1,3-thiazine at the exocyclic nitrogen atom and with 2-benzylamino-5,6-dihydro-4H-1,3-thiazine at the nitrogen atom in the ring. The structure of the reaction intermediates was elucidated, and their cyclization into 1-benzyl-2-aryl-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazinium bromides was performed.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. II. Synthesis of 5-(alkyl)(phenyl)-4-acylisoxazoles and 6,7-dihydro-1,2-benzisoxazol-4(5H)-ones

The reaction of open-chain and cyclohexane sym-2-dimethylaminomethylene-1,3-diones with hydroxylamine hydrochloride in refluxing methanol gave in good to moderate yields a series of 5-(alkyl)(phenyl)-4-acylisoxazoles and 6,7-dihydro-1,2-benzisoxazol-4(5H)-ones, respectively. As 3-unsubstituted isoxazoles, all these compounds easily isomerized with sodium methoxide to the corresponding 2-cyano-1,3-diones in high yields.     

Synthesis of 2,3,10,11 -tetraalkoxy-substituted tetrahydrobenzo [a] naphtho [1,2-g] quinolizines

2 Four3,10,11-tetraalkoxy-substituted 5,6,15,15a-tetrahydro-8H-benzo[a]naphtho[1,2-g]-quinolizines were prepared by the Pictet-Spengler cyclization of the respective 1-(6,7-dialkoxy-2-naphthylmethyl)-6,7-dialkoxy-1,2,3,4-tetrahydroisoquinolines. The latter compounds were obtained by a chemical reduction of the corresponding dihydro compounds, which, in turn, were formed by a Bischler-Napieralski cyclization of the appropriate amides.     

Cycloaddition reactions of 1,3-benzothiazines—I. : Reactions of 2-phenyl-4-H and 4-phenyl-2H-1,3-benzothiazine derivatives with substituted acetyl chlorides

6,7-Dimethoxy-2-phenyl-4$\text{H}$-1,3-benzothiazine (1) and 6,7-dimethoxy-4-phenyl-2$\text{H}$-1,3-benzothiazine (2) react with substituted acetyl chlorides to give linearly, and new angularly condensed β-lactam derivatives (4,5). Heating of the latter compounds with hydrogen chloride in anhydrous ethanol leads to the formation of the corresponding 4$\text{H}$- and 2$\text{H}$-1,3-benzothiazinium chloride, respectively. The configurations of these compounds (the mutual positions of the substituents relative to the β-lactam ring) were determined by ¹H and ¹³C studies, also making use of the aromatic solvent-induced shifts.     

Synthesis of 1H,3H-imidazo[1,5-c]thiazole-5,7-[6H,7aH]-dione and 7,8-dihydro-5-H-imidazo[1,5-c][1,3]thiazine-1,3-[2H,8aH]-dione and derivatives

1H,3H-Imidazo[1,5-c]thiazole-5,7-[6H,7aH]-dione and the corresponding 7-thione derivatives as well as 7,8-dihydro-5H-imidazo[1,5-c][1,3]thiazine-1,3-[2H,8aH]-dione and the corresponding 3-thione derivatives were synthesized starting from L -cysteine and DL -homocysteine thiolactone, respectively. The second group of bicyclic compounds represents a new heterocyclic ring system. The structures of the compounds were confirmed by spectroscopic studies and elemental analyses.     

Synthesis of quinazolino-1,3-benzothiazine derivatives

The ring-closure reactions of N-(3,4-dimethoxyphenylthiomethyl)-2-nitrobenzamide derivatives 5a,b with phosphoryl chloride gave 4-(2-nitrophenyl)-2H1,3-benzothiazine derivatives 7a,b , which on reduction yielded 4-(2′-aminophenyl)-3,4-dihydro-2H-1,3-benzothiazines 8a,b. Reaction of these compounds with phosgene led to a new heterocyclic ring system, 6H,8H-quinazolino[3,4-c][1,3]benzothiazine derivatives 9a,b. The structures of the title compounds were proved via their ir and nmr (¹H, ¹³C) spectra.     

Synthesis of oxazole and furan derivatives via Rh2(OAc)4-catalyzed C≡X bond insertion of cyclic 2-diazo-1,3-diketones with nitriles and arylacetylenes

Abstract

A convenient and efficient procedure for the synthesis of 2-substituted-6,7-dihydrobenzo[d]oxazol-4(5H)-ones and 2-aryl-6,7-dihydrobenzofuran-4(5H)-ones through a Rh₂(OAc)₄-catalyzed C≡X (X?=?N, C) insertion of cyclic 2-diazo-1,3-diketones with nitriles and aromatic alkynes has been developed. This reaction uses readily available starting materials and stable cyclic 2-diazo-1,3-diketone compounds, with desired products formed in good to high yields. A tentative mechanism involving a C≡X bond insertion and 1,5-dipolar electrocyclization/ring opening and cyclization sequence for this reaction is proposed.     

Synthesis and biological study of novel 5-{(4-(6,7-dihydrothieno-[3,2-c]pyridin-5(4H)-ylsulfonyl)phenylamino)-methyl}quinolin-8-ol and its metal complexes

A novel 5-((4-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)phenylamino)methyl)quinolin-8-ol(HTPSMQol) was synthesized by optimized reaction of 4-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)aniline with 5-chloromethyl-8-hydroxy-quinoline hydrochloride(CMHQ).Also complexes of HTPSMQol were prepared by using various M(Ⅱ) metal salts.All compounds were analyzed by spectroscopic techniques and screened against various strains of microorganisms.The results showed higher antimicrobial activity of HTPSMQol compared to its metal complexes and comparable with Ciprofloxacin.     

The m/z 91 rearrangement ion in the mass spectra of some 1,4-benzodiazepines

With the aid of isotope labeling and by substituent shifts, the relatively strong m/z 91 ion in the mass spectra of 7-chloro-2-methoxy-5-phenyl-3H-1,4-benzodiazepine and related compounds was shown to contain the 5-phenyl ring and the 3-CH₂ group. Mechanisms involving the opening of the 7-membered ring and the migration of the phenyl ring from C-5 to C-3 are postulated for the formation of this ion. This rearrangement ion was also observed in the mass spectra of some 1-alkyl-7-chloro-1,3-dhydro-5-phenyl-2H-1,4-benzodiazepin-2-ones.     

Synthesis of 7-[4-alkoxy-3-methoxy(hydroxy)phenyl]-10,11-dihydrobenzo[c]acridin-8(7H,9H,12H)-ones and 4-(8-oxo-7,8,9,10,11,12-hexahydrobenzo[c]acridin-7-yl)-2-methoxy(ethoxy)phenyl esters of carboxylic acids

Reactions of azomethines (Schiff bases) prepared from vanillin and vanillal ethers and 1-naphthylamine with cyclohexane-1,3-dione in butanol afforded in 40–64% yields 7-[4-alkoxy-3-methoxy(hydroxy)phenyl]-10,11-dihydrobenzo[c]acridin-8(7H,9H,12H)-ones and 4-(8-oxo-7,8,9,10,11,12-hexahydrobenzo[C]acridin-7-yl)-2-methoxy(ethoxy)phenyl esters of carboxylic acids. The reaction products presumably formed by the rearrangement of the azomethine adduct with the cyclohexane-1,3-dione proceeding by the type of Hofmann-Martius rearrangement. The structure of compounds synthesized was confirmed by the elemental analysis, UV, IR, and ¹H NMR spectra.     

Natural product chemistry. Part 153 . Synthesis and possible anticancer activity of 8-nitronoracronycine

Since the strategy for the synthesis of 9-, 10- and 11-nitronoracronycine [3,4] could not be applied to the 8-nitronoracronycine 9 , we here report the preparation of the latter by a fusion of methyl 2-amino-6-nitrobenzoate 2 and phloroglucinol 3 . The fusion of 2 and 3 gave 1,3-dihydroxy-8-nitro-9(10H)-acridinone 6 . Subsequent methylation, demethylation and reaction with 2-chloro-2-methyl-3-butyne afforded the desired 8-nitronoracronycine 9 . Compound 9 , 1,3-dimethoxy-10-methyl-8-nitro-9(10H)-acridinone 7 and 1,3-dihydroxy-10-methyl-8-nitro-9(10H)-acridinone 8 were tested by the National Cancer Institute (NCI) for possible anticancer activity.     

Synthesis, reactions, and biological activity of 1,4-benzothiazine derivatives

Abstract  

6,7-Dimethoxy-2H-1,4-benzothiazin-3(4H)-one reacts with dimethylformamide dimethylacetal (DMF-DMA) to give the novel enaminone 2-(dimethylaminomethylene)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-one. The reaction of the latter with various active methylene compounds afforded pyrido[3,2-b][1,4]benzothiazines. Also, coupling of the enaminone with diazotized aniline derivatives gave 2-(arylhydrazono)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-ones. Spectral data indicated that the latter compounds exist predominantly in the hydrazone tautomeric form. In addition, coupling of the enaminone with diazotized heterocyclic amines afforded tetra- and pentaheterocyclic ring systems. The antitumor and antimicrobial activity of some of the synthesized compounds was screened.     

Heterocycles. 7. A facile synthesis of 6,7-dihydroxs-1,4-dithiepins

Ring expansion by dehydration of 1,3-dithian-2-ylmethanols gives 6,7-dihydro-5H-1,4-dithiepins.     

Regioselective Synthesis of Polyfluoroalkyl Substituted 6,7‐Dihydrobenzisoxazolones

Regioselective methods for synthesis of hitherto unreported both 6,7‐dihydro‐1,2‐benzisoxazol‐4(5H)‐ones and 6,7‐dihydro‐2,1‐benzisoxazol‐4(5H)‐ones with perfluoroalkyl or halogenodifluoromethyl substituents have been developed. 3‐Polyfluoroalkyl‐6,7‐dihydro‐1,2‐benzisoxazol‐4(5H)‐ones were prepared by the cyclocondensation of 2‐polyfluoroalkanoylcyclohexane‐1,3‐diones with hydroxylamine. The regioisomeric 3‐polyfluoroalkyl‐6,7‐dihydro‐2,1‐benzisoxazol‐4(5H)‐ones were synthesized by the transformation of 2‐polyfluoroalkanoylcyclohexane‐1,3‐diones into their vinylogous chlorides, followed by the interaction of obtained crude 3‐chloro‐2‐polyfluoroalkanoyl‐2‐cyclohexen‐1‐ones with sodium azide in dimethylformamide.     

Synthesis and structure determination of isomeric 7- and 8-chloro-1,5-benzodiazepine derivatives

Reaction of 4-chloro-1,2-benzenediamine with 3,3-dimercapto-1-phenyl-2-propen-1-one afforded, as expected, a mixture of 7-chloro and 8-chloro-1,3-dihydro-4-phenyl-2H-1,5-benzodiazepine-2-thione. After separation of the two components and further reaction, their structure was established by chemical degradation of 7-chloro-2-(2-diethylaminoethylthio)-4-phenyl-3H-1,5-benzodiazepine to 5-chloro-1,3-dihydro-1-methyl-2H-benzimidazol-2-one. The structure was also confirmed by single X-ray analysis of 7-chloro-2-(2-diethylaminoethylthio)-4-phenyl-3H-1,5-benzodiazepine.     

Synthesis of 1-substituted 3-nitroquinolin-4(1H)-ones

A versatile synthetic method for preparing 1-substituted 3-nitroquinolin-4(1H)-ones from corresponding 2-fluoro-α-nitroacetophenones is demonstrated by the synthesis of 6,7-difluoro derivatives 7a-c . The method involves sequential treatment of the starting nitroacetophenone with triethyl orthoformate and the appropriate amine, followed by a nucleophilic cyclization reaction under mild conditions. The C-7 fluorine atom of 7 can be displaced by cyclic amines. Substituted 6-fluoro-7-(4-methyl-1-piperazinyl)-3-nitroquinolin-4(1H)-ones 8a-c were prepared in this way.     

Three New Arylnaphthalide Lignans from the Aerial Parts of Bupleurum marginatum Wall. ex DC.

Three new arylnaphthalide lignans, 5‐(4‐hydroxy‐3‐methoxyphenyl)furo[3′,4′: 6,7]naphtho[2,3‐d]‐1,3‐dioxol‐6(8H)‐one ( 1 ), 10‐(4‐hydroxy‐3‐methoxyphenyl)furo[3′,4′: 6,7]naphtho[1,2‐d]‐1,3‐dioxol‐9(7H)‐one ( 2 ), and 10‐(3,4‐dimethoxyphenyl)‐6‐hydroxyfuro[3′,4′: 6,7]naphtho[1,2‐d]‐1,3‐dioxol‐9(7H)‐one ( 3 ), together with two known ones, chinensin ( 4 ) and isodiphyllin ( 5 ), were isolated from the aerial parts of Bupleurum marginatum Wall . ex DC. The structures of the three new lignans were established by means of NMR spectroscopic studies, including HQSC, HMBC, and ROESY.