3-羟基-4-甲基-5-乙基-2(5H)-呋喃酮的合成

报道了以草酸二乙酯为原料,制备具有焦糖香味的香料化合物3-羟基-4-甲基-5-乙基-2(5H)-呋喃酮的方法:首先乙基溴化镁与草酸二乙酯通过格氏反应,以约50%产率生成2-氧代丁酸乙酯,然后其在碳酸钾的作用下发生缩合反应,以约94%产率得到3-羟基-4-甲基-5-乙基-5-乙氧羰基-2(5H)-呋喃酮,再通过水解、脱羧反应,得到3-羟基-4-甲基-5-乙基-2(5H)-呋喃酮.路线总收率约36%.     

Functional derivatives of thiophene

The nitration of 3-ethoxycarbonyl-4-hydroxy-2-methyl- and 4-chloro-3-ethoxycarbonyl-2-methylthiophenes has given the corresponding 5-nitro derivatives of thiophene. The 4-chloro-3-ethoxycarbonyl-2-methylthiophene was synthesized by the decarboxylation of 3-chloro-4-ethoxycarbonyl-5-methylthiophene-2-carboxylic acid, which is formed by the oxidation of 3-chloro-4-ethoxycarbonyl-5-methylthiophene-2-carbaldehyde.For Communication IV, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1024–1025, August, 1973.     

Regio- and stereodirection of addition of tetrazole to α,β-acetylenic γ-hydroxy nitrile: synthesis of 1- and 2-(<Emphasis Type="Italic">Z</Emphasis>)-(2-cyanoethenyl- 1-hydroxyalkyl)tetrazoles

Using the example of the reaction of tetrazole with 4-hydroxy-4-methyl-2-pentynonitrile, conditions were found under which (Z)-4-hydroxy-4-methyl-3-(1H-tetrazol-1-yl)2-pentenonitrile was formed by regio- and stereoselective addition at atom N(1) of tetrazole (yield 85%, selectivity 95%).     

Reaction of 2-methyl-3-ethoxycarbonyl-4-hydroxythiophene with hydrazines

2-Methyl-3-ethoxycarbonyl-4-(N,N-dimethylhydrazino)thiophene (II) and 2-methyl-3-ethoxy-carbonyl-4-(N-phenylhydrazino)thiophene (III) are formed by the action of substituted hydrazines — N,N-dimethylhydrazine and phenylhydrazine — on 2-methyl-3-ethoxycarbonyl-4-hydroxythiophene (I). At the same time, the thiophene ring of hydroxythiophene I undergoes hydrazinolysis under the influence of hydrazine hydrate to form 3-mercaptomethyl-4-ethoxycarbonyl-5-methylpyrazole (IV). Structure IV was proved by IR, UV, and PMR spectroscopy and by hydrogenolysis of IV to the known 3,5-dimethyl-4-ethoxycarbonylpyrazole (V).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 759–761, June, 1971.     

Reaction of 2-Alkoxypropenals with 2-Mercaptoethanol

The reaction between 2-alkoxypropenals and 2-mercaptoethanol was studied at 20 and 60°C by means of ^1HNMR and GC-MS methods. Under kinetically controlled conditions (20°C, 7-30 days) with no catalyst the addition of 2-mercaptoethanol to 2-alkoxypropenals occurs along Markownikoff rule. The arising 2'-hydroxyethylthio-2-alkoxypropanal undergoes isomerization into the 2-hydroxy-3-alkoxy-3-methyl-1,4-oxathiane that at heating in the presence of catalytic amounts of acids is converted into 2-methyl-2-formyl-1,3-oxathiolane. The reaction of 2-alkoxypropenals with 2-mercaptoethanol at heating (60°C, 3 h) in the presence of acids affords 2-methyl-2,2'-bi(1,3-oxathiolane) even at 2-mercaptoethanol deficit. At the double excess of the latter the 2-methyl-2,2'-bi(1,3-oxathiolane) was obtained in quantitative yield. The presumable schemes of conversion of 2-hydroxy-3-alkoxy-3-methyl-1,4-oxathiane into 2-methyl-2-formyl-1,3-oxathiolane and 2-acetyl-1,3-oxathiolane are discussed.     

Synthesis and characterization of some new pyridines,thieno[2,3-b] pyridines and pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones bearing styryl moiety

3-Cyano-5-ethoxycarbonyl-6-methyl-4-styrylpyridine-2(1H)-thione ( 3 ) was prepared by reaction of 2-cyano-5-phenylpenta-2,4-dienethioamide ( 2 ) with ethyl acetoacetate or by multicomponent reaction of cinnamaldehyde ( 1 ), cyanothioacetamide and ethyl acetoacetate in a moderate yield. Reaction of compound 3 with some N-aryl-2-chloroacetamides, in the presence of sodium acetate, gave the corresponding 2-(N-arylcarbamoylmethylsulfanyl)-3-cyano-5-ethoxycarbonyl-6-methyl-4-styrylpyridines 4a-f . When compounds 4a-f were subjected to Thorpe-Ziegler reaction conditions, they converted into the corresponding 3-amino-5-ethoxycarbonyl-2-(N-arylcarbamoyl)-6-methyl-4-styrylthieno[2,3-b]pyridines 5a-f . Compounds 5a,e,f were reacted, in turn, with 2,5-dimethoxytetrahydrofuran to furnish the corresponding 3-(pyrrol-1-yl)thieno-pyridines 6a,e,f . Reactions of 5a-f with triethyl orthoformate or nitrous acid were also carried out and their products were identified. Structural formulas of all synthesized compounds was characterized and confirmed on the basis of their elemental and spectral analyses.     

4-Hydroxy-2-quinolinones 128. Bromination of N-allyl-4-hydroxy-2-oxo-1,2-dihydroquinolines and pyridines unsubstituted in position 3

Bromination of N-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline and N-allyl-5-ethoxycarbonyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine is accompanied not only by closing of a five membered oxazole ring but also by a second bromination of the 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]-derivatives formed at position 4. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1365–1373, September, 2007.     

Reactions of Tri(1-propenyl)amine with Elemental Sulfur

The reaction of tri(1-propenyl)amine with elemental sulfur in bipolar aprotic solvent (DMF'DMSO) at 50°C within 1.5 h furnished 5-methyl-2-ethylthiazole in 62% yield. 2H'5H-5-methyl-2-ethyl-thiazole, 2-hydroxy-5-methylbenzaldehyde were found among the side products. The formation paths of thecompounds obtained are suggested.     

Researches on 2, 1, 3-thia- and selenadiazole

4-Hydroxy-, 4-hydroxy-5-methyl-, 4-hydroxy-7-methylbenzo-2,1,3-thiadiazoles are polymorphous.4-Hydroxybenzo-2,1,3-thiadiazole (I), 4-hydroxy-5-methyl- and 4-hydroxy-7-methylbenzo-2, 1, 3-thiadiazoles (II and III) melt at 114–115°, 110–112°, 100–102° C, respectively, after recrystallization from water [2–4], but after recrystallization from petrol ether [5] they melt at 128–129°, 124–125°, and 119–120° C [5]. In this connection we recrystallized these phenols repeatedly from petrol ether after recrystallizing them from water, and their melting points rose as expected [5]. On the other hand, the compounds with melting points 128–129°, 124–125°, 119–120° C (ex petrol ether), after repeated crystallization from water melted at 114–115°, 110–112°, 100–102° C, respectively.For Part XXXVIII see [1].     

Reactions of methyl (E,Z)-2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)-amino-3-dimethylaminopropenoate with heteroarylhydrazines. 2-(2-Benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-heteroarylhydra-zonopropanoates and 1-heteroaryl-4-ethoxycarbonyl-3-phenylpyrazoles

In the reaction of methyl (E,Z)-2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopro-penoate ( 1 ) with heteroarylhydrazines 2 in ethanol in the presence of catalytic amounts of hydrochloric acid two types of products were formed: methyl 2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-heteroaryl-hydrazonopropanoates 4 in 73-86% yield and 1-heteroaryl-4-ethoxycarbony-3-phenylpyrazoles 5 in 5-16% yield.     

Reactions of 1-methyl-derivatives of 2-oxo-1,2,3,4-tetrahydropyrimidine with phosphorus pentachloride and phosphorus oxychloride

In the reaction of 4-phenyl- and 4,6-diphenyl-1-methyl-2-oxo-5-ethoxycarbonyl-1,2,3,4-tetrahydropyrimidines with phosphorus pentachloride, oxidation and dealkylation takes place in addition to chlorination and as a result one obtained 4-phenyl- and 4,6-diphenyl-1-methyl-5-ethoxycarbonyl-2-pyrimidones and also 4-phenyl-, (4,6-diphenyl)-5-ethoxycarbonyl-2-chloropyrimidines. 1,6-Dimethyl-2-oxo-4-phenyl-5-ethoxycarbonyl-1,2,3,4-tetrahydropyrimidine in the same reaction gives 1-methyl-2-oxo-4-phenyl-5-ethoxycarbonyl 6-dichloromethyl-1,2,3,4-tetrahydropyrimidine, together with 6-chloromethylene- and 6-dichloromethylene-1-methyl-2-oxo-4-phenyl-5-chloro-5-ethoxycarbonylhexahydropyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 668–671, May, 1987.     

Derivatives of 4-hydroxy-5,6,7,8-tetrafluorocoumarin in reactions with o-aminothiophenol

The derivatives of 4-hydroxy-5,6,7,8-tetrafluorocoumarin in reactions witho-aminothiophenol yield products of S-substitution at C⁷ atom, 7-substituted 5,6,8-trifluorocoumarins afford benzothiazoles as a result of cleavage of the pyrone cycle, 2-methyl-3-ethoxycarbonyl-5,6,7,8-tetrafluorochromone undergoes acidic cleavage to 2-(2-hydroxy-3,4,5,6-tetrafluorophenyl)benzothiazole. S-Substituted coumarins in alkaline media suffer decomposition to acetophenone. In acidic media 3-iminoacetyl-4-hydroxy-5,6,8-trifluoro-7-(2-aminophenylthio)coumarin affords 2-methyl-5,6,8-trifluoro-7-(2-aminophenylthio)chromone. In condensation of 4-hydroxy-5,6,8-trifluoro-7-(2-aminophenylthio)coumarin in the presence of NaH was isolated 4-hydroxy-5,6-difluoro-2H-pyrano[6,5-a]phenothiazin2-one.     

Synthesis of some 3-EthoxycarbonyI-5-hydroxy-4-oxo-2-pyrroline derivatives from 3(2H)furanones

A number of 3-ethoxycarbonyl-5-hydroxy-2-methyl-5-or-1,5-substituted 4-oxo-2-pyrrolines have been prepared, respectively, by the action of ammonium hydroxide or primary aliphatic amines on 2-arylidene or 2-N-acetyl-N-arylaminomethylene-4-ethoxycarbonyl-5-methyl-3(2H)furanones. The structures of these prepared compounds have been determined by spectroscopic data and chemical means.     

Synthesis and study of 4-aminopyrazolones (5)

Some 4-N-thioureido- and -ureido derivatives are synthesized by reacting 1-phenyl-3-methyl-4-aminopyrazolone(5) hydrochloride at 40–50°, in alcohol solution, with potassium thiocyanate in the presence of sodium acetate plus carbon disulfide, phenylisothiocyanate, and hexamethylenediisocyanate. Acetylation of 1-phenyl-3-methyl-4-aminopyrazolone(5) with C₁–C₈ aliphatic carboxylic acids takes place under more drastic conditions at 100–150°, to give the corresponding 1-phenyl-3-methyl-4-acylaminopyrazolones(5), isolated in 40–60% yield. The UV spectra of the compounds studied are investigated.For Part I, see [1].     

Synthesis of Derivatives of 8-Cyano-6-ethoxycarbonyl-3-hydroxy-5-methylimidazo[1,2-a]pyridine and 9-Alkoxycarbonyl- (or 9-Carboxy)-3-ethoxycarbonyl-2-methyl-10H-benzo[b]-1,8-naphthyridine-5-one from the Reaction of 2-Chloro-5-ethoxycarbonyl-6-methylnicotinonitrile with Amino Acids

2-Substituted 8-cyano-6-ethoxycarbonyl-3-hydroxy-5-methylimidazo[1,2-a]pyridine was formed from the interaction of 2-chloro-5-ethoxycarbonyl-6-methylnicotinonitrile with -amino acids in DMF. The same nitrile on boiling with anthranilic acid or its esters in butanol gave, respectively, 2-(2-carboxyanilino)- or 2-(2-alkoxycarbonylanilino)-5-ethoxycarbonyl-6-methylnicotinonitriles which cyclized on heating in PPA to give 9-alkoxycarbonyl(or 9-carboxy)-3-ethoxycarbonyl-2-methyl-10H-benzo[b]-1,8-naphthyridin-5-ones.     

Abnormal ring closure and oxidation in situ of 2-hydroxy-5-nitrobenzaldehyde in the hantzsch synthesis

The Hantzsch condensation of 2-hydroxy-5-nitrobenzaldehyde, ethyl acetoacetate and ammonia gave the hitherto unknown 2-methyl-3-ethoxycarbonyl-4-ethoxycarbonylmethyl-6-(2-hydroxy-5-nitrophenyl)-pyridine via an unusual condensation and oxidation in situ.     

Amination of isomeric bromo-1-methylnitropyrazoles

A method was developed for the synthesis of 5-bromo-1-methyl-4-nitropyrazole from 1-methylpyrazole. In the reaction with 25% aqueous ammonia at 180–190 °C, 5-bromo-1-methyl-4-nitropyrazole is readily converted to 5-amino-1-methyl-4-nitropyrazole; the production of 4-amino-1-methyl-5-nitropyrazole from 4-bromo-1-methyl-5-nitropyrazole requires the presence of a copper catalyst; under the same conditions in the amination of 4-bromo-1-methyl-3-nitropyrazole, 4-amino-1-methyl-3-nitro- and 1-methyl-3-nitropyrazoles are formed in a 23 ratio.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1672–1675, December, 1983.     

Cycloaddition of 1-Aryl-3-trimethylsiloxy-1,3-butadienes in the Synthesis of Natural Quinone Analogs

7-Hydroxy-5-(2-methoxyphenyl)-2-methyl-6-R-1,4-naphthoquinones, 8-hydroxy-1-(2-methoxyphenyl)-3-oxo-1,2,3,4-tetrahydro-9,10-anthraquinone, and 2-ethoxycarbonyl-8-hydroxy-1-(2-methoxyphenyl)-3-trimethylsiloxy-1,1a,4,4a-tetrahydro-9,10-anthraquinone were synthesized by reactions of 1-(2-methoxyphenyl)-2-R-3-trimethylsiloxy-1,3-butadienes with 2-bromo-5-methyl-1,4-benzoquinone and juglone. 1-Aryl-2-ethoxycarbonyl-3-trimethylsiloxy-1,3-butadienes reacted with 1,4-naphthoquinone to afford 1-aryl-2-ethoxycarbonyl-3-hydroxy-9,10-anthraquinones and their 4,4a-dihydro derivatives.     

Alkyl nitrate nitration of active methylene compounds. Nitration of 1-methyl4-piperidone, 1-methyl-2-pyrrolidinone and 1,3-dimethyl-2-pyrrolidinone

The reaction of 1-methyl-4-piperidone ( 1 ) with amyl nitrate in the potassium tert-butoxidetetrahydrofuran system gave dipotassium 5-methyl-2-oxo-1,3-piperidinedinitronate ( 4 ) in 78% yield. Similar treatment of 1-methyl-2-pyrrolidinone ( 2 ) afforded potassium 3-methyl-2-oxopyrrolidinenitronate ( 7 ) in 85% yield. In contrast, the nitration of 1,3-dimethyl-2-pyrrolidinone ( 3 ) led to opening of the lactam ring with the formation of amyl 2-aza-2-methyl-5-nitrohexanoate ( 10 ) in 40% yield. Acidification of disalt 4 did not cause ring opening but gave the dipolar ion of 1-methyl-3-nitro 4-hydroxy-5-aci-nitro-Δ³-tetrahydropyridinium (6).     

2-乙氧羰基-3-甲基-4,5-四亚甲基吡咯的合成

以乙酰乙酸乙酯(1)为原料,在醋酸中与亚硝酸钠通过肟化反应制得N-羟基亚胺乙酰乙酸乙酯(2);2在醋酸缓冲溶液中经锌粉还原后与环己酮加成环化合成了2-乙氧羰基-3-甲基-4,5-四亚甲基吡咯(3),其结构经1H NMR,IR和元素分析表征。较适宜的反应条件为:1100 mmol,n(Zn)∶n(1)=2.9∶1.0,在醋酸中回流反应,总收率39%;以多步反应的最佳反应条件进行"一锅煮"合成3,收率50%。