Metal Phthalocyanines with Undecyloxybenzoic Acid Residues,and Their Mesomorphic Properties

Acylation of 4-amino-5-nitro-, 5-amino-4-bromo-, 5-amino-4-phenoxy-, 4-hydroxy-5-nitro-, 3- and 4-hydroxyphtalonitriles with p-undecyloxybenzoyl chloride gave the corresponding acyl derivatives which were used to prepare copper and cobalt phthalocyanines. Physicochemical properties of the resulting products were studied. The synthesized metal complexes all exhibit mesomorphic properties.     

Naphth[1,2-d]oxazole intermediates in the preparation of 3-hydroxy-4-(1-alkyl-3-methyl-5-hydroxy-4-pyrazolyl)-azo-1-naphthalenesulfonamide dyes

Acylation of 4-amino-3-hydroxy-1-naphthalenesulfonic acid ( 3 ) with benzoyl chloride in pyridine gave pyridinium 3-hydroxy-4-(N-benzoylamino)-1-naphthalenesulfonate ( 12 ) which was converted by thionyl chloride followed by diethylamine into N,N-diethyl-2-phenylnaphth[1,2-d]oxazole-5-sulfonamide ( 14 ). The naphthoxazole moiety was hydrolyzed with potassium hydroxide and the resulting N,N-diethyl-4-amino-3-hydroxy-1-naphthalenesulfonamide ( 11 ) coupled with 1-alkyl-3-methyl-5-pyrazolones. The 2-phenylnaphth[1,2-d]oxazole intermediates and various by-products were investigated.     

Electron transfer reactions. Reaction of tetracyclone,tetraphenylfuran and related substrates with potassium

The reaction of tetracyclone (1) with potassium in THF gave a mixture of benzoic acid (4), tetraphenylfuran (5) and cis-1,2-dibenzoylstilbene (6). The reaction of 1 with potassium in oxygen-saturated THF gave a mixture of 2-hydroxy-2,4,5-triphenyl-3(2H)furanone (3), 4, 5 and 6, whereas the reaction of 1 with potassium superoxide gave a moderate yield of 3,4,5,6-tetraphenyl-2-pyrartone (7), besides 3, 4, 5, and 6. The reaction of tetraphenylfuran (5) itself with potassium in THF gave a mixture of 6, 1,2,3,4-tetraphenylbutan-1-one (9), 2,3-diphenyl-1-indenone (10) and 2,3-epoxy-4-hydroxy-2,3,4-tnphenyltetralone-l (11), whereas practically no reaction occurred on treatment of 5 with potassium superoxide. Treatment of 10 with potassium in THF, however, gave a mixture of 4, dibenzo[a,c]-13-fluorenone (13), 2,3-diphenyl-2-hydroxyl-1-indanone (14) and 2,3-diphenylbenzofuran (15). A similar mixture of products consisting of 4, 13, 14 and 15 was obtained when the reaction of 10 with potassium was carried out in oxygen-saturated THF or when 10 was treated with potassium superoxide. Treatment of 2,3-diphenyl-2,3-epoxy-1-indanone (16) with potassium on the other hand, gave 10 in excellent yield. Cyclic voltammetric studies have been carried out to measure the reduction potentials of 1, 5, 10 and 16 in the generation of their radical anions. The radical anions of 1, 5, 10 and 16 were also generated pulse radiolytically in methanol and their spectra showed absorption maxima in the region 320–380 nm.     

Microbiological transformation of bicyclic monoterpenes by Absidia orchidis (Vuill.) Hagem. 2. Hydroxylation of fenchone and isofenchone. 18. Section on reactions with microorganisms

(+)-Fenchone ( 3a ) was transformed to 6-exo-hydroxy-fenchone (6β-hydroxy-1, 3, 3-trimethyl-nor-bornan-2-one) ( 1a ) and to 5-exo-hydroxy-fenchone 5β-hydroxy-1, 3, 3-trimethyl-nor-bornan-2-one ( 4a ) by the mycelium of Absidia orchidis (Vuill.) Hagem. The structure of the two products was proven by a detailed analysis of the NMR. spectra of the corresponding acetyl derivatives 2a and 5a respectively, and by CrO₃-oxidation. 1a yielded the β-diketone 6a , and 4a the diketone 8a. Whereas 8a was stable to alkali 6a was cleaved to the cyclopentane carboxylic acids 7 and 9 . — Incubation of (—)-fenchone ( 3b ) yielded the enantiomeric hydroxylation products 1b and 4b in the same ratio. - (—)-Isofenchone ( 11a ) was transformed by Absidia orchidis into the two epimers 6-endo-hydroxy-isofenchone (6β-hydroxy-1, 5, 5-trimethyl-nor-bornan-2-one) ( 12a ) and 6-exo-hydroxy-isofenchone (6β-hydroxy-1, 5, 5-trimethyl-nor-bornan-2-one) ( 10a. ) CrO₃-oxidation of both 10a and 12a gave the same β-diketone 6a. - (+)-Isofenchone gave the corresponding enantiomeric hydroxy derivatives 10b and 12b on incubation with Absidia orchidis.     

Synthesis of thiopyrano[2,3-d] pyrimidines and thieno[2,3-d]pyrimidines

The reaction of 4-chloro-5-cyano-2-methylthiopyrimidine (I) with ethyl mercaptosuccinate (II) in refluxing ethanol containing sodium carbonate has afforded diethyl 3-amino-2-(methyl-thio)-7H-thiopyrano[2,3-d]pyrimidine-6,7-dicarboxylate (IV). Displacement of the methylthio group in IV with hydrazine gave the corresponding hydrazino derivative which underwent Schiff base formation with benzaldehyde or 2,6-dichlorobenzaldehyde. Treatment of IV in refluxing acetic anhydride afforded the corresponding diacetylated amino derivative. Partial saponification of IV with sodium hydroxide gave 5-amino-2-(methylthio)-7H-thiopyrano-[2,3-d]pyrimidine 6,7-dicarboxylic acid 6 ethyl ester (VIII). The reaction of 4-amino-6-chloro-5-cyano-2-phenylpyrirnidine (XI) with II resulted in the formation of ethyl 4-amino-6-(ethoxy-carbonyl)-5,6-dihydro-5-amino-2-phenylthieno[2,3-d]pyrimidine-6-acetate (XIII) which when subjected to hydrolysis gave ethyl 4,5-diamino-2-phenylthieno[2,3-d]pyrimidine-6-acetate isolated as the hydrochloride (XIV). Diazotization of IV with sodium nitrite in acetic acid unexpectedly afforded diethyl 5-(acetyloxy)-6,7-dihydro-6-hydroxy-2-(methylthio)-5H-thio-pyrano[2,3-d]pyrimidine-6,7-diearboxylate (XV). Several structural ambiguities were resolved by ir and pmr spectra.     

The synthesis of 3-deazapyrimidine nucleosides related to uridine and cytidine and their derivatives

Condensation of 2,4-bis(trimethylsilyloxy)pyridine ( 1 ) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide ( 2 ) gave 4-hydroxy-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 3 ). Deblocking of 3 gave 4-hydroxy-1-β-D-ribofuranosyl-2-pyridone (3′-deazauridine) ( 4 ). Treatment of 4 with acetone and acid gave 2′,3′-O-isopropylidene-3-deazauridine ( 6 ). Reaction of 4 with diphenylcarbonate gave 2-hydroxy-1-β-D-arabinofuranosyl-4-pyridone-O₂←2′-cyclonucleoside ( 7 ) which established the point of gylcosidation and configuration of 4 . Base-catalyzed hydrolysis of 7 gave 4-hydroxy-1-β-D-arabinofuranosyl-2-pyridone (3-deazauracil arabinoside) ( 12 ). Fusion of 1 with 3,5-di-O-p-toluyl-2-deoxy-D-erythro-pentofuranosyl chloride ( 5 ) gave the blocked anomeric deoxynucleosides 8 and 10 which were saponified to give 4-hydroxy-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazauridine) ( 11 ) and its α anomer ( 9 ). Condensation of 4-acetamido-2-methoxypridine ( 13 ) with 2 gave 4-acetamido-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 14 ) which was treated with alcoholic ammonia to yield 4-acetamido-1-β-D-ribofuranosyl-2-pyridone ( 15 ) or with methanolic sodium methoxide to yield 4-amino-1-β-D-ribofuranosyl-2-pyridone (3-deazacytidine) ( 16 ). Condensation of 13 and 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride ( 17 ) gave the blocked nucleoside 22 which was treated with base and then hydrogenolyzed to give 4-amino-1-β-D-arabinofuranosyl-2-pyridone (3-deazacytosine arabinoside) ( 23 ). Fusion of 13 with 5 gave the blocked anomeric deoxynucleosides 18 and 20 which were deblocked with methanolic sodium methoxide to yield 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazacytidine) ( 21 ) and its a anomer 19 . The 2′-deoxy-erythro-pentofuranosides of both 3-deazauracil and 3-deazacytosine failed to obey Hudson's isorotation rule but did follow the “quartet”-“triplet” anomeric proton splitting pattern in the ¹H nmr spectra.     

Reaction of 2,6-dibutylaminohepta-2,5-dien-4-one with malononitrile

Malononitrile reacted with the title compound to give 6-amino-5-cyano-2-(3,3-dicyano-2-methylallylidene-4-methyl-2H-pyran (3). Treatment of 3 with hot 80% sulfuric acid yielded 4,7-dimethyl-56-hydroxy-2(1H)quinolone. With concentrated aqueous sodium hydroxide, 3 gave 5-amino-3,6-dicyano-4,7-dimethyl-2(1H)quinolone and 5-amino-6-carbamoyl-3-cyano-4,7-dimethyl-2(1H)quinolone. The reaction of 3 with hydrochloric in acetic acid gave a mixture of 6-amino-3,7-dicyano-2,8-dimethyl-4-quinolizone and 3-cyano-4-methyl-6-(3,3-dicyano-2-methylallyl)-2-pyrone. Compound 3 also reacted with methylamine, butylamine and piperidine to give 8-amino-5-cyano-4-methyl-2-pyridone, 6-bulylamino-5-cyano-4-methyl-2-pyridone and 5-eyano-4-methyl-6-piperidino-2-pyridone respectively.     

The synthesis of a pyrido[3,4-d]pyrimidine analog of pteroic acid

A multistep synthesis of ethyl 5-amino-2-methyIpyridine-4-carboxylate (5a) starting from ethyl acetopyruvate and nitroacetamide is described. The condensation of 5a with benzoylcyanamide gave 2-amino-3-benzoyl-6-methylpyrido[3,4-d]pyrimidin-4(3H) one (10), which could be hydrolyzed in alkali to give 2-amino-4-hydroxy-6-methylpyrido[3,4-d]pyrimidine (9). Free radical bromination of 10 in bromotrichloromethane gave a mixture of the bromo- and chloromethyl- derivatives (11). Fusion of 11 with ethyl p-aminobenzoate, followed by alkaline hydrolysis gave the corresponding pteroic acid analog (12).     

Reaction of 5-amino-1-phenylpyrazole-4-carbonitriles with dimethyl acetylenedicarboxylate. Synthesis and structural determination of trimethyl 4,8-dioxo-1-phenyl-4,5,5a,8-tetrahydro-1H-pyrazolo[3,4-e]indolizine-5,5a,6-tricarboxylate derivatives

The reaction of 5-amino-1-phenylpyrazole-4-carbonitriles 1a-c with dimethyl acetylenedicarboxylate in the presence of potassium carbonate in dimethyl sulfoxide gave trimethyl 4,5,5a,8-tetrahydro-1-phenyl-4,8-dioxo-1H-pyrazolo[3,4-e]indolizine-5,5a,6-tricarboxylate derivatives 3a-c from the basic solution. The products were formed by a double Michael reaction of 1 with dimethyl acetylenedicarboxylate followed by cyclization to the cyano group. The structure of product 3a was established by X-ray crystallography.     

Synthesis of 6-substituted pyrimidines by the wittig reaction. II . Via 2-acetamido-4-hydroxy-5-phenylbutylpyrimidine-6-carboxaldehyde

Wittig condensations of both stabilized and unstabilized ylides were successfully achieved with 2-acetamido-4-hydroxy-5-phenylbutylpyrimidine-6-carboxaldehyde (XI); functionalized Wittig reagents derived from dichloroacetone, ethyl 4-iodobutyrate, 4-bromobutyronitrile, phenylpropyl bromide, 3-bromopropylphthalimide, p - nitrobenzyl bromide, and p-nitrocinnamyl bromide were used. The resultant 6-substituted pyrimidines could be further transformed by reduction of the 6-side-chain double bond. Successful Wittig reactions were achieved with XI where the corresponding 2-amino-4-hydroxy-5-phenylbutylpyrimidine-6-carboxaldehyde (X) with its less electrophilic aldehyde group failed to give isolable yields of condensation products.     

The Synthesis of 3,5-Diamino-1,2,4-oxadiazoles. 1st Communication

Reaction of the 1-substituted-3-cyano-isothioureas 6 with hydroxylamine gave mixtures of the 5-amino-3-substituted-amino-1,2,4-oxadiazoles 1 and the isomeric 3-amino-5-substituted-amino-1,2,4-oxadiazoles 8 in which 1 usually predominated. The structural assignment of these products is discussed. In a second method, the 2-hydroxy-1-methyl-1-phenyl-guanidine 15 was converted to the corresponding 3-disubstituted-amino-5-trichloromethyl-1,2,4-oxadiazole 16 , a precursor to the 5-amino derivatives 17 by nucleophilic displacement of the trichloromethyl group.     

2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤的合成

报道了2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤(1)的合成, 通过对起始原料2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧甲基丁基)嘌呤(2)水解脱去乙酰基, 得到2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤(3). 化合物3与三甲胺乙醇溶液在混合溶剂[V(THF)∶V(DMF)＝3∶1]中反应得到相应的氯化铵盐4, 然后与KF在DMF溶剂中反应, 得到化合物1. 产品经UV-vis, IR, ¹H NMR, ¹⁹F NMR和MS表征. 考察了反应温度、氟化试剂等因素对氟化反应的影响, 为6位含氟的嘌呤核苷类化合物的合成提供了一种直接、简易的新方法.     

Pyrazolo[3,4-b]pyridines. I. Xanthine and isoguanine analogs derived from 1-methylpyrazolo[3,4-b]pyridine

The synthesis of 4,6-dihydroxy-l-methylpyrazolo[3,4-b Jpyridine ( 2 ) and 4-amino-6-hydroxy-1-methylpyrazolo[3,4-b] pyridine ( 3 ) as analogs of xanthine and isoguanine has been accomplished from ethyl 5-amino-1-methylpyrazole-4-carboxylate ( 4 ) and 5-amino-1-methylpyrazole-4-carbo-nitrile ( 6 ), respectively.     

Die Acylierung von 5-Amino-1 H-1, 2, 4-triazolen. Eine 13C-NMR.-Studie

The Acylation of 5-Amino-1 H-1,2,4-triazoles. A ¹³C-NMR. Study The acylation of 3-substituted-5-amino-1 H-1,2,4-triazoles (1) with methyl chloroformate or dimethylcarbamoyl chloride yielded mainly 1-acyl-5-amino-1,2,4-triazoles ( 2 and 3 ). Acylation of 3-methyl-, 3-methoxy- and 3-methylthio-5-amino-1 H-1,2,4-triazole ( 1b , 1c and 1d ) with methyl chloroformate gave up to 10% of the 1-acyl-3-amino-1,2,4-triazoles. For the unsubstituted 5-amino-1,2,4-triazole (1a) , a (1:1)-mixture of the 3- and 5-isomers 2a and 4 was obtained in dioxane in the presence of triethylamine. No 4-acylated product was detected in contrast to earlier reports. The structures of the reaction products were determined with the aid of proton coupled ¹³C-NMR. spectra using the corresponding N-methyl-1,2,4-triazoles as reference compounds.     

PHOSPHONOMETHYLATION OF AMINOALKANOLS PREPARATION OF 4-(PHOSPHONOMETHYL)-2-HYDROXY-2-OXO-1,4,2-OXAZAPHOSPHORINANES1

Abstract

Treatment of aminoalkanols 1 with phosphorous acid and formaldehyde in presence of conc. hydrochloric acid gave mixtures of [(2-hydroxy alkyl)imino] dimethylene diphosphonic acids 3 and 4-(phosphonomethyl)-2-hydroxy-2-oxo-1,4,2-oxazaphosphorinanes 2 from which 2 were isolated as crystalline solids. Similar treatment of 2-amino-2-methyl-1,3-propanediol 8 gave a complex mixture from which dimethylene diphosphonic acid of 5-amino-5-methyl-1,3-dioxane 9 was isolated. 2-Aminoethanethiol, when subjected to phosphonomethylation. gave an unexpected novel quarternary nitrogen product 11. N-Alkylaminoalkanols 4 on phosphonomethylation gave 3:1 mixtures of [N-alkyl-N-(2-hydroxyalkyl)amino] methane phosphonic acid 6 and N-alkyl-2-hydroxy-2-oxo-1,4,2-oxazaphosphorinane 5. Treatment of the crude mixtures of 5 and 6 with aqueous sodium hydroxide gave disodium salts of [N-alkyl-N-(2-hydroxyalkyl)amino] methanephosphonic acid 7. The ratio of the cyclic to the open chain structures obtained as well as the formation of any unexpected novel products is dependent on the structure of the aminoalkanol that is phosphonomethylated. The ¹H, ¹³C and ³¹P spectra are reported for all new compounds.     

Derivatives of 2,3-Dihydrocyclopenta[d] pyrido[1,2-a] pyrimidin-10(1H)one

The annulation of 2-amino-3-hydroxy-, 2-amino-3-carboxy-, and 2-amino-3-methylpyridine with ethyl cyelopenlanone-2-earboxylate led to the 5-hydroxy-, 2 , 5-carboxy-, 3, and 5-methyl-, 4 , derivatives of the 2,3-dihydrocycloperita[d]pyrido[1,2-a]pyrimidin-10(1H) one heterocycle. Alkylation of 2 with α-bromotolue, ne gave the 5-benzyloxy derivative.     

Synthesis and structure of some substituted 2-amino-4-aryl-7-propargyloxy-4H-chromene-3-carbonitriles

A series of 2-amino-7-hydroxy-4H-chromene-3-carbonitriles 4a–l were synthesized through three-component reaction using sodium carbonate as a catalyst. The reaction was carried out in 96% ethanol-water medium (1:20 ratio in volume). Propargyl ether compounds 5a–l of these chromene-3-carbonitriles were successfully synthesized from corresponding hydroxyl chromene derivatives by reaction with propargyl bromide. Two different procedures were applied in this process: the procedure that used potassium carbonate in dried acetone and the procedure that used sodium hydride in dried DMF. The latter gave the ethers 5a–l in higher yields. The single-crystal X-ray structure of propargyl ether 5g has been recorded.     

Synthesis of 4-chloro-7-ethoxy-2(3H)-benzoxazolone-6-carboxylic acid

As a part of metabolic studies of mosapride ( 1 ), a potential gastroprokinetic agent, the synthesis of 4-chloro-7-ethoxy-2(3H)-benzoxazolone-6-carboxylic acid ( 7 ) as a derivative of 4-amino-5-chloro-2-ethoxy-3-hydroxybenzoic acid ( 6 ), which has served a benzoic acid part of the metabolites 4 and 5 , is described. Treatment of methyl 3-amino-4-substituted amino-5-chloro-2-ethoxybenzoate derivatives 11a-c with sodium nitrate in acidic medium gave the benzotriazole derivatives 13x,y instead of the objective 3-hydroxy counterpart. The synthesis of 7 started from o-vanillin acetate ( 15 ) and proceeded through the intermediates 2-hydroxy-3-methoxy-4-nitrobenzaldehyde ( 18 ), methyl 4-amino-2,3-dihydroxybenzoate ( 23 ), and methyl 7-hydroxy-2(3H)-benzoxazolone-6-carboxylate ( 30 ). Compound 30 was alternatively prepared from 23 via methyl 4-ethoxycarbonylamino-2-ethoxycarbonyloxy-3-hydroxybenzoate ( 29 ), which is the product resulting from the migration of the ethoxycarbonyl group of methyl 4-amino-2,3-diethoxycar-bonyloxybenzoate ( 27 ).     

Fused s-triazino heterocycles. XVIII. 1,3,4,7,11c-Pentaazabenz[de]anthracene and 1,3,4,6,7,11c-hexaazabenz[de]anthracene. Two new ring systems

The reaction of 2-amino-4-chloro-6-methylpyrimidine ( 3a ) with trimethylacetyl chloride gave 4-chloro-6-methyl-2-trimethylacetamidopyrimidine ( 5 ). This latter compound with excess anthranilonitrile gave in one step 2-t-butyl-5-methyl-1,3,4,7,11c-pentaazabenz[de]anthracene ( 6a ). To prepare 2-t-butyl-5-dimethylamino-1,3,4,6,7,11c-hexaazabenz[de]anthracene ( 6b ) it was found necessary to first react 2-amino-4-chloro-6-dimethylamino -5 -triazine ( 3b ) with anthranilonitrile to yield the intermediate product 2-amino-4(2-cyanoanilino)-6-dimethylamino-s-triazine ( 4 ). Reaction of the latter with trimethylacetyl chloride gave 6b .     

9-Hydroxy-2-methyl-4H-pyrido[1,2-α] pyrimidin-4-one and its derivatives

2-Amino-3-(o-bromobenzyloxy)pyridine ( 1 ) and ethyl acetoacetate gave 9-(o-bromobenzyl-oxy)-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 2 ) in 2% yield. When 1 and methyl β-amino-crotonate ( 3 ) were reacted, benzyl ether cleavage occurred and the products were 9-hydroxy-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 4 ) and its ammonium salt ( 5 ). These observations led to an alternative synthesis in which 2-amino-3-pyridinol ( 6 ) and either 3 or methyl acetoacetate, ( 8 ) in diethylbenzene at 185° gave 4 in 86 and 87% yields, respectively, and the anion of 4 and o-bromobenzyl bromide gave 2 in 61% yield. Even in diethylbenzene at 185°, 1 and 8 gave only trace amounts of 2 . Thus, o-bromobenzylation of the 3-hydroxyl group in 6 markedly decreased the reactivity of the amino group in 6 toward reactions with acetoacetic esters.