Action de O- et N-nucléophiles sur les sels de phényl-3 benzopyrylium-1

3-Phenyl-1-benzopyrylium percholorates 1a, 1i react exculusively at C-2 with ethanol and isopropyl alcohol, affording mixed acetals 2a, 3a, 3i . Aqueous ammonia gives symmetrical secondary amines 4a, 4b or bis(3-phenyl-2H-1-benzopyran-2-yl)amines, while with aqueous aliphatic amines (40%) bis-acetals 5a, 5b or 2,2′-oxy-bis(3-phenyl-2H-1-benzopyrans) are characterized. In some other acidic conditions, 5a and 5b are also obtained.     

The reactions of 4-dicyanomethylene-2-phenyl-4H-1-benzopyran and some benzologs with nucleophiles

4-Dicyanomethylene-2-phenyl-4H-1-benzopyran (1) reacts with primary amines under mild conditions to give 4-imino-3-alkyl-5-alkylimino-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]-pyridine derivatives which, in turn, are hydrolyzed with acid to 4-imino-3-alkyl-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. When more vigorous conditions are employed for the reactions of 1 with primary amines, Dimroth rearrangements take place and the products are derivatives of 4-alkyl- (or aryl)amino-5-alkyl- (or aryl)imino-2-phenyl-5H-[1]benzopyrano-[3,4-c]pyridine. The latter compounds are hydrolyzed by acid to the corresponding 5-pyridone derivatives. The reaction of 1 with piperidine gives 2-phenyl-4-piperidyl-5H-[1]benzopyrano-[3,4-c]pyridin-5-one. Sodium methoxide reacts with 1 to give 3-cyano-2-methoxy-4-(2-hydroxyphenyl)-6-phenylpyridine. Two benzologs of 1 have been allowed to react with primary and secondary amines and the products are analogous to those obtained from 1 .     

The reactions of some pyraiiylideneiminium salts with amines. II

The iminium salt, N,N-dimethyl-N-[2-(2-phenyl-4H-l-benzopyran-4-ylidene)ethylidene] imin-ium perchlorate ( 3 ), reacts with secondary amines by exchanging the dimethylimino group for the added amine. Primary amines also reacted with 3 in the same manner. The bis iminium salts, N,N,N',N'-tetramethyl-N,N'-[2-(2-phenyl-4H-l-benzopyran-4-ylidene)-1,3-propanediylidene]-bis(immium perclilorate) ( 4 ) and the corresponding thiapyran derivative ( 5 ), react with ammonia to give 5-dimethylamino-2-phenyl-5H-1-benzopyrano[3,4-c]pyridine ( 10 ) and the thia analog 11 . The reactions of 4 and 5 with primary amines give 3-alkyl-5-dimethylamino-2-phenyl-5H-l-beiizopyrano[3,4-c]pyridinium perclilorate salts or the corresponding thiapyrano compounds. Compounds 4 and 5 react with secondary amines by exchanging the dimethylimino groups with the secondary amine and addition of the amine at the 2-position of the pyran or thiapyran ring.     

Synthesis of 3-substituted-4-phenyl-2-thioxo-1,2,3,4,5,6,7,8-octahydrobenzo[4,5]thieno[2,3-á]pyrimidines

The reactions between 3-benzoyl-2-isothiocyanato-4,5,6,7-tetrahydrobenzo[b]thiophene and hydrazine or primary amines have been studied. The products obtained were identified as derivatives of 4-phenyl-2-thioxo-2,3,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidine. Their easy reduction with sodium borohydride provided a useful method for the synthesis of 3-substituted-4-phenyl-2-thioxo-1,2,3,4,5,6,7,8-octahydrobenzo[4,5]thieno[2,3-d]pyrimidines. Both kind of compounds were evaluated as potential analgesic, anti-inflammatory and anti-arthritic agents.     

Reactions of some pyranylidene esters with amines

The reactions of 4-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)-2,6-diphenyl-4H-pyran ( 1 ) with primary amines gave the corresponding 1-substituted 1,4-dihydropyridine derivatives. The related benzo derivative of 1 (12) and primary amines gave 3-substituted 3,4-dihydro-2-phenyl-5H-[1]benzopyrano[3,4-c] pyridine-4,5-dione derivatives. With secondary amines, 12 gave 2-phenyl-4H,5H-pyrano[3,4-c] [1]benzopyrane-4,5-dione, and with isopropylamine, N,N-dimethylhydra-zine, and methanolic potassium hydroxide, 12 gave 4-phenacylcoumarin. Some reaction intermediates were isolated which indicate probable reaction paths. The reactions with amines were extended to a naphtho derivative of 1 (19) and to a thia homolog of 12 (24).     

Synthesis and Antimicrobial Activity of Some New 5-Arylazothiazole,Pyrazolo[1,5-a] Pyrimidine, [1,2,4]Triazolo[4,3-a]Pyrimidine,and Pyrimido[1,2-a]Benzimidazole Derivatives Containing the Thiazole Moiety

1-(2-(4,5-Dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-5-phenylpyrazol-1-yl)-4-substituted thiazol-5-yl)-2-phenyldiazene were synthesized from hydrazonoyl halides and 3-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide in ethanolic triethylamine. Also, pyrazolo[5,1-a]pyrimidines, 2,3,6-trisubstituted pyridines, and pyrazolo[3,4-d]pyridazines were obtained from sodium salt of 3-hydroxy-1-(4-methyl-2-phenylthiazol-5-yl)prop-2-en-1-one and different heterocyclic amines. All structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, and alternative synthetic route whenever possible. The newly synthesized compounds were tested towards different microorganisms.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis of 2-hetaryl-6H-pyrazolo[3,4-d]-1,2,3-triazoles

A novel efficient synthesis of 2-hetaryl-4-methyl-6-phenyl-6H-pyrazolo[3,4-d]-1,2,3-triazoles was achieved by the reaction of 5-amino-3-methyl-4-nitroso-1-phenyl-1H-pyrazole with heterocyclic amines followed by air oxidation in the presence of cupric acetate.     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. XI. Cyclizations with epoxides

4-Toluenesulfonyl isocyanate cyclized with 1,2-epoxy-3-phenoxypropane and 2,3-epoxypropyl 4-methoxyphenyl ether, respectively, to give 3-(4-toluenesulfonyl)-5-phenoxymethylene-2-oxazolidone ( I ) and 3-(4-toluenesulfonyl)-5-(4-methoxyphenoxymethylene)-2-oxazolidone ( II ). Compounds I and II were hydrolyzed in 2 M sodium hydroxide solution to the corresponding uncyclized hydroxy amides, VII and VIII. Compound I was remarkably stable toward 6 M hydrochloric acid and amines. Styrene oxide, 1,2-epoxybutane, 3-chloro-1,2-epoxypropane, and 1-methoxy-2-methylpropylene oxide reacted with the isocyanate to afford 3-(4-toluene-sulfonyl)-4-phenyl-2-oxazolidone (III), 3-(4-toluenesulfonyl)-4-ethyl-2-oxazolidone ( IV ), 3-(4-toluenesulfonyl)-5-chloromethyl-2-oxazolidone ( V ), and 3-(4-toluenesulfonyl)-4,4-dimethyl-5-methoxy-2-oxazolidone ( VI ), respectively. The yield of VI was constant over a temperature range of 25–90°.     

Studies on the syntheses of azole derivatives. Part VII. Syntheses of 1 -phenyl-Δ2-1,2,4-triazolin-5-one derivatives [studies on the syntheses of heteroeyclic compounds. CD XI]

Bromination of 3-methyl-1-phenyl-Δ²-1,2,3-lriazolin-5-one (II) and its 4-phenyl derivative III afforded the corresponding I-(p-Bromophenyl) derivatives IV and V, respectively. (Chlorination of the 4-phenyl derivative III gave I-(P-chlorophenyl) derivative VI. In addition, 3-N-subsuituted-carhamoyl-1,2,4-triazolin-5-ones(XII, XIII, and XIV) were synthesized by the Schotten-Baumann reaction of 3-carboxy-1-phenyl-Δ²-1,2,4-triazolin-5-one (XI) with various amines.     

An anomalous reaction of 7-chloro-2-hydrazono-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine with sodium acetate and 1,1′-carbonyldiimidazole

The addition of 7-chloro-2-hydrazono-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine 3 to a mixture of sodium acetate and 1,1′-carbonyldiimidazole 1 at room temperature gave, in moderate yields, carbonyl-1,1′-bis[7-chloro-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ylidene hydrazone] 7 instead of the expected 2-acetylhydrazono-7-chloro-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine 4 .     

Synthesis of pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5-ones. Cyclization reaction of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid with acetic anhydride

Treatment of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid (X) with acetic anhydride under refluxing conditions afforded 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]-pyrimido[4,5-d]pyrimidin-5-one acetate (IX). The intermediate X was prepared from 4-chloro-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (V). The reaction of V with the sodium salt of 2-amino-3-hydroxypyridine at room temperature gave 4-(2-amino-3-pyridyloxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (VI). Treatment of VI with a hot aqueous sodium hydroxide solution and subsequent acidification gave X. Involvement of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecaroboxylic acid ethyl ester (VIII) (Smiles rearrangement product) as an intermediate in the above alkaline hydrolysis reaction of VI to X was demonstrated by the isolation of VIII and its subsequent conversion into X under alkaline hydrolysis conditions. Acetylation of VIII with acetic anhydride in pyridine solution gave 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester acetate (XI), which afforded IX on fusion at 220°. This alternative synthesis of IX from XI supported the structural assignment of IX. Fusion of VI gave 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]pyrimido]4,5-d]pyrimidin-5-one (VII). The latter was also obtained when VIII was fused at 210°. Acetylation of VII with acetic anhydride afforded IX.     

Reductive ring cleavage of 1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones with raney-nickel alloy. Synthesis of N-benzoyl-3-alkylamino-3-phenylalanine amides from rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone

rel-(4R,5R)-4-Benzoylamino-5-phenyl-3-pyrazolidinone ( 1 ) was alkylated at position 1 with carbonyl compounds 2a-g . The corresponding rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone-1-azomethine imines 3a-g , were treated with sodium borohydride to give rel-(4R,5R)-1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones 4a-g . Reduction of pyrazolidinones 4a-g with Raney-nickel alloy in methanolic potassium hydroxide furnished rel-(4R,5R)-N-benzoyl-3-alkylamino-3-phenylalanine amides 5a-f .     

2-Alkyliden-1, 3-dithia-Heterocyclen aus 5-Sulfonyl-1, 2-dithiol-3-onen und Alkoholaten

Asymmetrically substituted 5-sulfonyl-1, 3-dithiafulvenes (9a–g), all of which have the same configuration (called α), are obtained by reaction of 4-chloro-5-sulfonyl-1, 2-dithiol-3-ones (3a–e) with sodium alkoxides. Side-products formed are 4-chloro-5-alkoxy-1, 2-dithiol-3-ones (5a and 5b), 3, 5-bis-alkylidene-1, 2, 4-trithiacyclopentanes (21 and 22), and (in some instances) minor amounts of compounds 33, 34, or 35. Reaction of 4-phenyl-5-methylsulfonyl-1, 2-dithiol-3-one with sodium methoxide results in the formation of 4-phenyl-5-methoxy-1, 2-dithiol-3-one (5c), the two cis-trans-isomers of 2, 4-bis-alkylidene-1, 3-dithiacyclobutane 24 and 25, and the 2, 5-bis-alkylidene-1, 2, 4, 5-tetrathiacyclohexane 26. Some conceivable reaction mechanisms are discussed, and proof is given for the structure of the major compounds. By treating 4-chloro-5-(2′-chloro-ethylthio)-1, 2-dithiol-3-one with sodium methoxide, the 2-alkylidene-1, 3-dithiolane 13 is obtained. The sulfonyl groups of the 1, 3-dithiafulvenes 9a–g described may be easily replaced by hydrogen or secondary amines, yielding compounds 14, 16 and 19, respectively. When dissolved in strong acids and reprecipitated, asymmetrically substituted 2-alkylidene-1, 3-dithia compounds may be converted into mixtures of all possible cis-trans-isomers thereof. Those isomers may be separated by fractional crystallization. Isomers 31 (called β) of 9 a--g, and 32 of 16a, b, are obtained accordingly.     

4-Functionally Substituted 3-Heterylpyrazoles: VII. 3-Aryl(heteryl)-1-phenyl-4-pyrazolecarbonyl Isothiocyanates

3-Aryl(heteryl)-1-phenyl-4-pyrazolecarbonyl isothiocyanates were synthesized by treatment of 3-aryl(heteryl)-1-phenyl-4-pyrazolecarbonyl chlorides with lead, sodium, or ammonium thiocyanate. Their reactions with amines, hydrazines, and acylhydrazines gave the corresponding thioureas and thiosemi- carbazides.     

Nucleophilic Substitution in 1,5-Benzodiazepin-2-ones

The reaction of 3-bromo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one with cyclic amines gives 3-aminoalkyl-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one. Thiazolo[4,5-b][1,5]benzodiazepine was isolated along with the substitution product when thiourea was used.     

Trifluoromethyl Sulfones and Perfluoroalkanesulfonamides of the Azole Series

2-Phenyl-4-trifluoromethylsulfonylmethyl-2H-1,2,3-triazole was synthesized from 4-bromo-methyl-2-phenyl-2H-1,2,3-triazole and sodium trifluoromethanesulfinate CF₃SO₂Na. 1(2)-Ethyl-4-nitro-1(2)H-1,2,3-triazoles and 4-nitro-2-phenyl-2H-1,2,3-triazole were reduced to the corresponding amines. Intermediate 1,2-bis(1-ethyl-1H-1,2,3-triazol-4-yl)diazene 1-oxide exists as a mixture of syn and anti isomers, the former being stabilized via formation of a strong intramolecular hydrogen bond. The reduction of 2-ethyl-4-nitro-2H-1,2,3-triazole in the presence of HCl afforded the target 4-amino-2-ethyl-2H-1,2,3-triazole and also 4-amino-5-chloro-2-ethyl-2H-1,2,3-triazole. Treatment of alkyl-substituted 4-amino-1,2,3-triazoles with trifluoromethanesulfonyl chloride and pentafluoroethanesulfonyl chloride gave N-triazolyl-substituted trifluoromethane- and pentafluoroethanesulfonamides and -imides.     

4-benzoyl-5-phenyl-1,3-oxathiol-2-one. Synthesis and reaction with N-nucleophiles

The synthesis of 4-benzoyl-5-phenyl-1,3-oxathiol-2-ones 1 and the behaviour of 1a against several amines were investigated to afford aminomercaptoethenes 2 or thiocarbamates 3 , as well as complete cleavage to sulfur, dibenzoylmethane and the corresponding urea, depending on the nature of the N-nucleophile used.     

Synthesis of benzazepines and their rearrangement to quinolines and pyrrolo(2,3-b) quinolines

BECKMANN or SCHMIDT rearrangement of ethyl trans-4-oxo-1-phenyl-2-tetralincarboxylate ( 2 ) affords ethyl trans-2,3,4,5-tetrahydro-2-oxo-5-phenyl-1H-benzo [b] azepine-4-carboxylate ( 4 ). Mild treatment of trans-2,3,4,5-tetrahydro-1-methyl-2-oxo-5-phenyl-1 H-benzo-[b] azepine-4-carboxylic acid ( 7 ) with thionyl chloride and pyridine in dimethylformamide and subsequent reaction with an amine yields the corresponding benzazepine-4-carboxamide. If he it is applied during the preparation of the acid chloride, rearrangement occurs yielding cis and trans derivatives of hydrocarbostyril. 2,3,4,5-Tetrahydro-1,4-methano-1-methyl-5-phenyl-1 H-benzo-[b] azepinium chloride ( 25 ) reacts with primary or secondary amines to cis-tetrahydroquinoline derivatives. When heated above its melting point, trans-4,5-dihydro-2-methylamino-5-phenyl-3H-benzo-[b] azepine-4-carboxylic acid ( 29 ) rearranges with elimination of water to a mixture of cis-and trans-2,3,3a,4-tetrahydro-1-methyl-2-oxo-4-phenyl-1H-pyrrolo [2,3-b] quinoline ( 32 and 31 ). The reduction of 31 was investigated. The mechanisms of the rearrangements are discussed.     

Synthesis of novel 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones via azo coupling

Abstract  

6-(Substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones were prepared from β-aryl glutaconic acid, which, on fusion with aniline, results in 4-(4-ethoxyphenyl)-1-phenylpyridine-2,6(1H,5H)-dione. This, on further treatment with phosphorus oxychloride gave 6-chloro-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinone, and further treatment with secondary amines yielded 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones. These were subjected to azo coupling with different aryldiazonium chlorides furnishing two isomers, which were separated by column chromatography. All compounds were characterized by elemental analysis, and use of IR and NMR spectral data, and were evaluated for antimicrobial activity.     

Substituierte 2-Alkoxy-5-amino- und-2,5-diamino-imidazole aus Oxazol-2-yliden-cyanamiden

Summary N-Cyano-S-methyl-isothio-ureases (1) react with -halogen ketones (2) by ring closure yielding the (3H-oxazol-2-yliden)-cyanamides3. by ring transformation, 2-Alkoxy-5-amino-1-phenyl-3H-imidazol-4-yl)-ketones (4) are formed. Primary and secondary amines react with3 to give 2-N-alkylated (2,5-Diamino-1-phenyl-3H-imidazol-4-yl)-ketones.