Reaction of 5-(3,4-dimethoxyphenyl)pyrazine-2,3-dicarbonitrile with alcohol in the presence of base

5-(3,4-Dimethoxyphenyl)pyrazine-2,3-dicarbonitrile reacts with methanol to give addition products, 3-methoxyiminopyrazine-2-carbonitrile and 2-methoxyiminopyrazine-3-carbonitrile derivatives, and/or substitution products, 3-methoxypyrazine-2-carbonitrile and 2-methoxypyrazine-3-carbonitrile derivatives. The selectivity between the addition and substitution depends on solvent polarity, base, and reaction time. The experimental results are accounted for by the equilibrium between the starting dinitrile and the addition products, methoxyiminopyrazine.     

Photochemistry of host-guest complexes. VIII. The photoreaction of pyrazinedicarbonitrile derivatives having a crown ether moiety in the presence of an ω-diethylamino-1-alkanaminium salt

Irradiation of 5-[(benzo-18-crown-6)-4′-yl]pyrazine-2,3-dicarbonitrile and 5-(3,4-dimethoxyphenyl)pyrazine-2,3-dicarbonitrile in the presence of ω-diethylamino-l-alkanaminium ion caused the reductive decyanation to give pyrazinemonocarbonitrile derivatives. The reaction is initiated by a single electron transfer from the tertiary amino group of the diamine. The complex formation between the crown ether moiety and the ω- diethylamino-l-alkanaminium ion enhances the photoreaction.     

The syntheses of pteridin-2-one derivatives from diaminomaleonitrile (DAMN)

1,3-Dimethyl-4-iminopteridin-2-one, 1,3-dimethylpteridine-2,4-dione, 1-methylpteridine-2,4-dione, 4-alkoxy-1-methylpteridin-2-one, and 4-alkylamino-1-methylpteridin-2-one were synthesized from diaminomaleonitrile (DAMN) through pyrazine-2,3-dicarbonitrile. The synthetic procedures consist of the condensation of DAMN with glyoxal, the nucleophilic substitution of pyrazine-2,3-dicarbonitrile with methylamine, the reaction of 3-methylaminopyrazine-2-carbonitrile with electrophiles such as methyl isocyanate and methyl chloroformate in the presence of sodium hydride, and the transformation of 3-(methoxycarbonylmethyl)aminopyrazine-2-carbonitrile into the pteridine derivatives.     

Synthesis of pteridine derivatives related to folic acid and methanopterin from pyrazine-2,3-dicarbonitrile

Pteridine derivatives related to folic acid and methanopterin were synthesized by two methods. The first synthesis is initiated by the radical substitution of 5-methylpyrazine-2,3-dicarbonitrile (3) with the (N-acylanilino)alkyl radical to give 6-methyl-5-(N-acylanilino)alkylpyrazine-2,3-dicarbonitrile (9) and was followed by the substitution of the 2-carbonitrile with methylamine and further conversion to 1-methyl-2-amino-6-(N-acylanilino)-alkyl-7-methylpteridin-4(1H)-imine 11 by the action of guanidine. The second method is initiated by radical hydroxymethylation of 5-methylpyrazine-2,3-dicarbonitrile (3) to give 5-hydroxy-methyl-6-methylpyrazine-2,3-dicarbonitrile (15), followed by oxidation of the hydroxymethyl group, N-phenylimination, and the substitution of the 2-carbonitrile with methylamine to give 6-methyl-2-methyl-arnino-5-(N-phenylimino)methenylpyrazine-3-carbonitrile (18). The reduction of the imino group and the final cyclization with guanidine gives 2-amino-6-anilinomethyl-1,7-dimethylpteridin-4(1H)-imine (20).     

Synthesis of pyrazine-2,3-dicarbonitrile and 1,2,4-triazine-5（4H）-one derivatives from furan-2,3-diones

The reaction of furan-2,3-diones with S-methylisothiosemicarbazide hydroiodide yielded novel 1,2,4- triazine-5（4H）-ones, and reaction of furan-2,3-diones with diaminomaleonitrile led to the formation of pyrazine-2,3-dicarbonitrile derivatives, and the hydrolysis of these products led to the formation of more new pyrazine-2,3-dicarbonitrile derivatives. These compounds are potential herbicides and pesticides.     

The substitution reaction of pyrazine-2,3-dicarbonitrile derivatives with ammonia,amines, water and alcohols

5-Arylpyrazine-2,3-dicarbonitriles 1 and 2 give 2-alkylamino-5-arylpyrazine-3-carbonitriles 3 and 5 and 3-alkylamiono-5-arylpyrazine-2-carbonitriles 4 and 6 by the substitution reaction with amines but give only 3-aminopyrazine-2-carbonitrile derivative on the reaction with ammonia. The reaction of 5-arylpyrazine-2,3-dicarbonitriles ( 1 and 2 ) with alcohols in the presence of a base gives 2-alkoxypyrazine-3-carbonitrile derivatives 9 and 13 and 3-alkoxypyrazine-2-carbonitrile derivatives 10 and 14 . The reaction of water gives two pyrazinonecarbonitrile derivatives 11 and 12 . In these reactions the aryl groups on the pyrazine ring are 3,4-dimethoxyphenyl and benzo-15-crown-5.     

Synthesis and unusual chemical reactivity of certain novel 4,5-disubstituted 7-benzylpyrrolo[2,3-d][1,2,3]triazines.

The fact that only two pyrrolo[2,3-d][1,2,3]triazines heterocycles had been reported in the literature prompted us to initiate studies designed to provide additional members of this ring system. Initial attempts to prepare additional derivatives of the 7-unsubstituted pyrrolo[2,3-d][1,2,3]triazin-4-ones were limited by their low chemical reactivity. Subsequently, 7-benzyl-5-carboxamidopyrrolo[2,3-d][1,2,3]triazin-4-one (16) was prepared from diethyl 2-nitropyrrole-3,4,-dicarboxylate via an alkylation, ammonolysis, reduction and intramolecular diazocoupling sequence. Conversion of 16 into 7-benzyl-4-(1,2,4-triazol-1-yl)pyrrolo[2,3-d][1,2,3]triazine-5-carbonitrile (17) was accomplished, and nucleophilic displacements of the 4-triazol-1-yl group were studied. Treatment of 17 with NH3/CH3CN gave a mixture of 4-amino-7-benzylpyrrolo[2,3-d][1,2,3]triazine-5-carbonitrile (19) and 2-amino-1-benzylpyrrole-3,4-dicarbonitrile (21). A mechanism to account for the formation of this mixture is described along with studies on the effect that ammonia concentration and a TFA catalyst have on the product ratio. Compound 19 was converted into the 5-carboxamide and 5-thioamide derivatives of 19.     

Reaction of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with benzyltriethylammonium chloride

3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine was reacted with BnEt₃NCl (10?mol%) to give perchloro-9-thia-1,5,8,10-tetraazaspiro[5.5]undeca-1,4,7,10-tetraene (up to 18% yield), 4,5,6-trichloropyrimidine-2-carbonitrile (up to 44% yield) and four minor side products: 2,7-dichlorothiazolo[5,4-d]pyrimidine-5-carbonitrile, 2-(4-chloro-6H-thiazolo[5,4-c][1,2,6]thia-diazin-6-ylidene)malononitrile, 4,8-dichloropyrrolo[2′,1′:2,3]imidazo[4,5-c][1,2,6]thiadiazine-6,7-dicarbonitrile and 4,7-dichloro-[1,2,6]thiadiazino[3,4-b]thiazolo[5,4-e][1,4]diazepin-9(10H)-one. Single crystal X-ray studies support the structures of the minor products. Tentative rationale for the formation of these minor products and the synthesis of 8-bromo-4-chloropyrrolo[2′,1′:2,3]imidazo[4,5-c][1,2,6]thiadiazine-6,7-dicarbonitrile are presented.     

A convenient synthesis of 5-substituted-7-β-D-arabinofuranosylpyrrolo[2,3-d]pyrimidines structurally related to the antibiotics toyocamycin and sangivamycin

4-Amino-7-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carbonitrile ( 6a ), prepared from 2-ethoxymethyleneamino-5-bromopyrrole-3,4-dicarbonitrile ( 4 ), was debenzylated with boron trichloride to give ara-toyocamycin ( 6b ). Further functional group transformation of 6b provided a route to 4-amino-7-β-D-arabinofuranosylpyrrolo[2,3-d]pyrimidine-5-thiocarboxamide (ara-thiosangivamycin, 7a ), and the corresponding 5-carboxamidoxime 8a and 5-carboxamidine 8b derivatives. Phosphorylation of unprotected 7a with phosphorus oxychloride gave ara-thiosangivamycin 5′-monophosphate ( 7b ). 2′-O-Acetyl-ara-thiosangivamycin ( 10b ) was prepared as a prodrug by acetylation of 9a , followed by deprotection of the t-butyldimethylsilyl groups under acidic conditions without acyl migration.     

o-Quinonoid heterocycles: synthesis and crystal structure of 2,3-dicyano-5,7-bismethylthieno[3,4-b]pyrazine

2,3-Dicyano-5,7-bismethylthieno[3,4-b]pyrazine (5), has been obtained as a minor product from reactions of S-nucleophiles with 5,6-di(1-bromoethyl)pyrazine-2,3-dicarbonitrile (3), or from a condensation of 4-hydroxy-2,5-dimethyl-2,3-dihydrothiophen-3-one (4) with diaminomaleonitrile. The molecular structure of compound 5 has been confirmed by X-ray diffraction. A partial separation of charge causes a donor-acceptor type arrangement of the planar molecules in uniform parallel stacks with an interplanar spacing of 3.334(2) A at 100 K.     

An easy route for the synthesis of pyrazine-2,3-dicarbonitrile 5,6-bis-substituted derivatives using a palladium catalyst

An easy synthetic method for the preparation of pyrazine-2,3-dicarbonitrile 5,6-bis-substituted derivatives using Pd-catalyzed cross coupling reaction (Sonogashira, Suzuki, Heck) is described. The reaction conditions allow preparing symmetrical and unsymmetrical bis-substituted products in moderate to high yields, as precursors for the preparation of highly substituted symmetrical and non-symmetrical aza-phthalocyanines with well-defined spectral properties.     

Reaction of pyrazine-2,3-dicarbonitrile and 1,3-dimethyllumazine with alkyl radicals

Pyrazine-2,3-dicarbonitrile ( 1 ) reacts with alkyl radicals to give mono- 3 and di-alkylated pyrazine-2,3-dicarbonitriles 4 . Similarly 1,3-dimethyllumazine ( 2 ) reacts with alkyl radicals to give 7-alkyl-1,3-dimethyllumazines 8 as the major product. The reactivity of alkyl radicals decreases in the order tertiary, secondary, and primary, and 1 is more reactive than 2 in those radical substitution reactions.     

Synthesis and anticancer evaluation of some novel N,O,S heterocyclic compounds pendant to 3-methyl-5-cyano-6-(3,4-dimethoxyphenyl)pyrimidine and other related fused pyrimidines

The key starting compound 5-cyano-6-(3,4-dimethoxyphenyl)-2-thiouracil ( 1 ) was synthesized and allowed to undergo electrophilic substitution with methyl iodide to give the corresponding 6-(3,4-dimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile ( 2 ). Nucleophilic substitution on compound 2 with hydrazine hydrate led to the corresponding 2-hyrazinopyrimidone intermediate 3 . Compound 3 underwent several substitution and cyclization reactions with β-ketoester, β-ketone, alkyl halides, arylisothiocyanate, or aromatic aldehydes followed by cyclization reactions to give the corresponding N,O,S heterocyclic compounds incorporated into pyrimidine moiety and/or the related S-triazino[3,4-b]pyrimidine derivatives 4 - 18 . Anticancer evaluation of some representative examples of newly synthesized compounds was carried out against MCF-7, HCT116 cell lines. Some of the newly synthesized compounds showed significant activity.     

Reaction of 3,4,6-trioxoalkanoic acid esters with 2,4-dinitrophenylhydrazine

Methyl 3,4,6-trioxoalkanoates (3,4-dihydroxy-6-oxo-2,4-alkadienoates) reacted with 2,4-dinitrophenylhydrazine to give methyl 3,6-bis[(2,4-dinitrophenyl)hydrazinylidene]-4-oxoalkanoates or methyl {5-alkyl-2-hydroxy-1-(2,4-dinitroanilino)-3-oxo-2,3-dihydro-1H-pyrrol-2-yl }acetates. Alkyl 3,6-bis[(2,4-dinitrophenyl) hydrazinylidene]-4-oxoalkanoates were also synthesized by reaction of disodium 1-alkoxy-1,6-dioxoalka-2,4-diene-3,4-diolates with 2,4-dinitrophenylhydrazine.     

REACTIONS OF HYDRAZONOYL HALIDES 371: SYNTHESIS OF TRIAZOLO[4,3-a]PYRIMIDINES, 1,3,4-THIADIAZOLES AND 1,3,4-SELENADIAZOLES

1,2,4-Triazolo[4,3-a]pyrimidines, thiadiazolines and selenadiazolines synthesized via reactions of hydrazonoyl halides with each of ethyl 4-(3,4-dimethoxyphenyl)-6-methyl-2-methylthio-3,4-dihydropyrimidine-5-carboxylate (or ethyl 6-(3,4-dimethylphenyl)-4-methyl-2-thio1,3,6-trihydropyrimidine-5-carboxylate), ethyl 4-(2,3-dimethoxyphenyl)- 6-methyl-2-methylthio-3,4-dihydropyrimidine-5-carboxylate, potassium thiocyanate, potassium selenocyanate, and carbodithioates respectively.     

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 .     

一种合成娃儿藤碱重要中间体的新方法

以二乙酸碘苯（PIDA,2）为催化剂,分别由3,4-二甲氧基-α-（3,4-二甲氧苯基）一肉桂酸（5a）和（Z-2-（3,4-二甲氧苯基）-3-（3,4-二甲氧苯基）-丙烯腈（5b）为原料,合成了相应的2,3,6,7-四甲氧基-9-羧基菲（6a）和2,3,6,7-四甲氧基-9-氰基菲（6b）,经^1H NMR测试技术表征为关环产物,产率分别为65．83％和64．76％。     

Synthesis and Properties of 6-Amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

We have established that when 5-chloro-6-[cyano(2,3-dihydro-1-R-benzo[d]azol-2-yl)methyl]-2,3-pyrazinedicarbonitriles are reacted with nucleophilic reagents (aliphatic and aromatic amines, hydrogen sulfide), annelation of the five-membered ring occurs on the [b] face of the pyrazine with formation of 6-amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles and 6-amino-7-(1H-benzo[d]imidazol-2-yl)thieno[2,3-b]pyrazine-2,3-dicarbonitrile respectively. Further heating with excess of acylating reagent leads to formation of a novel heterocyclic system 1H-benzo[4,5]imidazo[1,2-c]pyrazino[2',3':4,5]pyrrolo[3,2-e]pyrimidine. Reaction of vicinal dinitriles with hydrazine hydrate leads to the novel system 1H-pyrrolo[2',3':5,6]pyrazino[2,3-d]pyridazine.     

Reaction of pyrazine-2,3-dicarbonitrile and 1,3-dimethyllumazine with the phthalimidoalkyl radical

A phthalimidoalkyl radical reacts with pyrazine-2,3-dicarbonitrile ( 1 ) to give mono- and diphthalimido-alkylpyrazine-2,3-dicarbonitriles 4 and 5 . A similar reaction with 1,3-dimethyllumazine ( 2 ) gave only monophthalimidoalkyl-1,3-dimethyllumazines 6 or 7 . Hydrazine degradation of 7-(3′-phthalimido)propyl-1,3-dimethyllumazine ( 6c ) gave a 7-(3′-amino)propyl derivative 8 but 7-phthalimidomethyl-1,3-dimethyllumazine ( 6a ) gave only 1,3-dimethyllumazine ( 2 ). Thus the phthalimidomethyl group can be used as a protection group of the pteridine nucleus.     

Facile and convenient synthesis of new thieno[2,3-b]-thiophene derivatives

A facile and convenient synthesis of bis(2-(1H-benzo[d]imidazol-2(3H)-ylidene)-3-oxopropanenitrile), bis((3-amino-5-(methylthio)-1H-pyrazol-4-yl)methanone) and bis(2-thioxo-1,2-dihydropyrimidine-5-carbonitrile) derivatives incorporating a thieno- [2,3-b]thiophene moiety via versatile, readily accessible diethyl 3,4-dimethylthieno-[2,3-b]thiophene-2,5-dicarboxylate is described.