Search

Synthesis and structure of novel ylidic thiabenzenes, 1-cyano-and benzoyl-2-methyl-2-thianaphthalenes (VI and X), are discussed. The reactions of VI with several electrophiles such as dimethyl acetylenedicarboxylate, methyl propiolate, diphenylcyclopropenethione, and diphenylcyclopropene are described together with the mechanisms of the reactions.

Die tetrasubstituierten [2.2]Paracyclophane 4a – e werden durch Cycloaddition der symmetrischen Acetylenderivate 2a – e an 1,2,4,5-Hexatetraen (1) dargestellt und ihre Konstitution und Konfiguration durch spektroskopische Methoden. Abbau- und Pyrolyseversuche bewiesen. Der Tetramethylester 4a wird zum Tetraalkohol 4g reduziert und die Tetracarbonsaure 4c in das Bisanhydrid 4f bzw. [2.2] Paracyclophan (4h) ubergefuhrt. Bei der Anlagerung von Propiolsaure-methylester (5a) an 1 werden alle isomeren disubstituierten [2.2]paracyclophanes 6 erhalten. Weitere symmetrische und unsymmetrische Acetylenderivate reagieren nicht mit 1. Preparation of [2.2]Paracyclophanes by Addition of Acetylene Derivatives to 1,2,4,5-Hexatetraene The tetrasubstituted [2.2]paracyclophanes 4a – e are formed by cycloaddition of the symmetrical acetylene derivatives 2a – e to 1,2,4,5-hexatetraene (1), and their constitution and configuration is established by spectroscopic methods, degradation and pyrolysis experiments. The tetramethyl ester 4a is reduced to the tetraalcohol 4g, and the tetracarboxylic acid 4c is converted to the bisanhydride 4f and [2.2] paracyclophanes (4h), respectively. All possible disubstituted [2.2] paracyclophanes 6 are obtained when methyl propiolate (5a) is added to. 1, whereas further symmetrical and unsymmetrical acetylene derivatives do not react with 1.

Die 2-Diazocycloalkanone 1a–f reagieren mt Dimethyl(acetylenidicarboxylat) uber die Pyrazolenin-Zwischenstufen 2a–f zu den Bicyclen 3a–f. Der Ubergang 2 3 wird als sigmatrope (1,5)-Acylverschiebung interpretiert. Im gleichen Sinne reagieren Acetylendicarbonitril, Hexafluor-2-butin, Butin-3-on und Methylpropiolat mit 1b zu 4a–d. – Die Bicyclen 3a–f werden in alkalischem Medium zu den Tricarbonsauren 5a–f hydrolysiert. Investigations on Diazo Compounds and Azides, XXI1). – Sigmatropic (1,5)-Acyl Shifts in the Cycladdition of 2-Diazocycloalkanones to Activated Acetylenes The 2-diazocycloalkanones 1a–f react with dimethyl acetylenedicarboxylate to give the bicyclic compounds 3a–f via the pyrazolenine intermediates –f The reaction 2 3 is interpreted as a sigmatropic (1,5)-acyl shift. In the same way acetylenedicarbonitrile, hexafluoro-2-butyne, butyn-3-one and methyl propiolate with 1 with formation of 4a–d, respectively. On hydrolysis in alkaline medium, the bicyclic compounds 3a–f give the tricarboxylic acids 5a–f.

3-Acylimino-1-methylbenzimidazolium betaines undergo 1,3-dipolar cycloaddition reactions with activated alkenes (methyl acrylate, acrylonitrile, and fumaronitrile) and methyl propiolate to produce 2-substituted 1-methylbenzimidazoles. The transformation involves the initial formation of a 1,3-dipolar cycloadduct followed by the NN bond cleavage. The primary adducts can be isolated from the reaction with methyl acrylate and acrylonitrile.

The stereochemistry of ring formation in the reaction of α-halogenoacrylic ester with organozinc compounds was studied using β-deuterated α-halogenoacrylic ester. A quantitative study was made on the steric course of every step of the reactions involved in the synthesis of methyl β-deuterio-α-bromoacrylate-cis-d1 starting from methyl propiolate. The mode of the CC double bond opening of methyl β-deuterio-α-bromoacrylate-cis-d1 to form dimethyl 1 -bromo-2-propyl-cis-1,2- cyclopropanedicarboxylate-d2 was confirmed to be cis and trans in a 50 to 50 ratio. Asymmetric syntheses for the cyclopropanedicarboxylic ester were possible, especially under the influence of chiral organozinc alkoxide system. A stepwise mechanism was postulated for the ring formation reaction.

3(5)-[Tetrazolyl-(l)]-pyrazol (2) und Pyrazolo[5.l-c]triazol (3) entstehen bei aquimolarer Umsetzung von Pyrazol-3(5)-diazoniumchlorid (1) mit Diazomethan. Bei zweifachem Uberschus an Diazomethan isoliert man neben 2 die isomeren N-Methyl-Derivate 10 und 11. Die Strukturen wurden auf Grund spektroskopischer Daten zugeordnet. Die Addition von Propiolsaureester an Diazo-cyclopentadien fuhrt zu einem blauen 2(1)H-Cyclopenta[c]pyridazin, das mit Azulen isoelektronisch ist. 1 reagiert mit Na-Azid zum noch unbekannten 3(5)-Azido-pyrazol. Reactions of 3(5)-Diazopyrazole, IV. 3(5)-(l-Tetrazolyl)pyrazole (2) and pyrazolo[5,1-c]triazole (3) are obtained by the reaction of pyrazole-3(5)-diazonium chloride (1) with an equimolar amount of diazomethane. With a twofold excess of diazomethane the two isomeric N-methyl derivatives 10 and 11 are isolated in addition to 2. The structures are based on spectroscopic data. The addition of methyl propiolate to diazocyclopentadiene leads to a blue 2(l)H-cyclopenta[c]pyridazine isoelectronic with azulene. 1 reacts with Na-azide to give the hitherto unknown 3(5)-azido-pyrazole.

In the presence of potassium t-butoxide or potassium hydroxide, propiolic acid adds two molecules of cyclohexanone to form the isomeric seq-cis- and seq-trans-7, 14-Dioxa-dispiro[5.1.5.2]pentadec-15-yliden-acetic acids IIa and IIIa, respectively. Methyl propiolate and cyclohexanone react analogously in the presence of potassium t-butoxide, yielding the corresponding esters. The structure of these condensation products follows from their physical properties and from degradation reactions to known compounds.

Die Reaktionen von Propiolsaure-methylester mit 3-Amino-benzisoxazol (1), 2-Amino-s-triazolo[1.5-a]pyridin (5), 3-Amino-indazol (13) und 2-Amino-benzimidazol (16) werden untersucht. Nur mit 1 entstehen beide isomeren kondensierten Pyrimidone (3 und 4), wahrend in allen anderen Fallen nur ein Isomeres isoliert wird (6, 14 oder 15, 17 oder 18). Syntheses with Heterocyclic Amines, X Reactions of some Heterocyclic Amines with Propiolic Ester The reactions of methyl propiolate with 3-aminobenzisoxazole (1), with 2-amino-s-triazolo-[1.5-a]pyridine (5), with 3-aminoindazole (13), and with 2-aminobenzimidazole (16) are studied. Only with 1 both isomeric condensed pyrimidones (3 and 4) are formed, whereas in all other cases only one pyrimidone is obtained (6, 14 or 15, 17 or 18).

5-Amino-tetrazol (1) reagiert mit Propiolsaureester zum Gemisch zweier isomerer 1 : 2-Addukte (3 und 4), mit Acrylsaureester zum 1 : 1-Addukt (5a), das thermisch oder durch alkalische Verseifung zum Oxo-tetrahydro-tetrazolo-pyrimidin 6 cyclokondensiert. Aus Acetylen-dicarbonsaureester und 1 entsteht das Isomerengemisch der Oxo-methoxycarbonyl-dihydro-tetrazolo-pyrimidine 7a und 8a sowie ein Azido-pyrimidin 9. Syntheses with Heterocyclic Amines, VIII Reactions of 5-Aminotetrazole with α.β-Unsaturated Esters 5-Aminotetrazole (1) reacts with methyl propiolate to give a mixture of two isomeric 1 : 2-adducts (3 and 4). Treatment of 1 with methyl acrylate yields a 1 : 1-adduct (5a), which cyclocondenses thermally or on alkaline saponification to afford the oxo-tetrahydro-tetrazolo-pyrimidine 6. Acetylene dicarboxylic ester reacts with 1 to give a mixture of isomeric oxo-methoxycarbonyl-dihydro-tetrazolo-pyrimidines 7a and 8a and an azidopyrimidine 9.

The addition of methyl propiolate to 4-keto-2a,3,4,5-tetrahydronaphthostyril (I) leads to the tetracyclic compound II.

The addition of substituted anilines to methyl propiolate produces labile cis-trans mixtures of enamines which can be isomerized by acid, solvent variation, and thermal techniques. Thermal cyclization of these enamines provides a synthesis of 4( lH)-quinolones.

The synthesis of a series of N-glycosyl-v-triazoles has been accomplished by the 1,3-dipolar cycloaddition of several glycosyl azides to methyl propiolate and propiolic acid. In most of the cases the two isomeric v-triazoles were obtained. Structural and anomeric configuration assignments for the N-glycosides obtained were made on the basis of NMR data. None of the compounds possessed appreciable biological activity against HeLa cells in culture and mouse Sarcoma 180.

3β-Acetoxy-20-keto-5,14,16-pregnatriene (I) reacts with hexafluorobutyne or with dimethyl acetylenedicarboxylate to form normal Diels-Alder adducts. However, reaction of I with methyl propiolate leads to the stereospecific formation both of normal Diels-Alder adduct and of a diadduct derived from homoconjugate addition of a second mole of dienophile to the monoadduct. The stereochemistry of the monoadduct was established by a correlation with 14α, 17α-ethano-16α-carbomethoxypregn-5-ene- 3β-ol-20-one acetate. The homoconjugate addition of methyl propiolate to methyl bicyclo [2.2.1]heptadiene-2-carboxylate is alsodescribed.

Synthesen und Eigenschaften der 4 isomeren Oxo-dihydro-s-triazolo-pyrimidine (3–6) werden beschrieben. Ihre Strukturzuordnung grundet sich auf Darstellungsweisen, ihr chemisches Verhalten sowie auf charakteristische Spektren. Oxo-dihydro-.s-triazolo[1.5-a]-pyrimidine (3, 5) sind die stabileren Isomeren, die durch thermische oder basenkatalysierte Umlagerung aus den [4.3-a]-Isomeren (4, 6) entstehen konnen. Aus 3-Amino-1.2.4-triazol (1) und Propiolsaure-methylester erhalt man die beiden Isomeren 4 und 3, in denen die Carbonyl-Gruppe der Amino-Gruppe benachbart ist, und, abhangig von den Reaktions-bedingungen, verschiedene Nebenprodukte. Die Struktur eines 1 :1-Additionsproduktes (7a) wird aus dem NMR-Spektrum abgeleitet. Syntheses with Heterocyclic Amines, II. Reactions of 3-Amino-1,2,4-triazole with Methyl Propiolate. Preparation and Characterization of four Isomeric Oxo-dihydro-s-triazolopyrimidines The syntheses and properties of the four isomeric oxo-dihydro-s-triazolopyrimidines (3–6) are described. Their structure determination is based on their formation, their chemical behaviour, and their characteristic spectra. Oxo-dihydro-s-triazolo[1,5- a]pyrimidines(3, 5) are the more stable isomers which can be formed by thermal or base-catalysed rearrangement of the [4,3-a]-isomers (4, 6). From 3-amino-1,2,4-triazole (1) and methyl propiolate the isomers 4 and 3 are obtained in which the carbonyl group is adjacent to the amino group. The structure of an 1 :l-addition product (7a) has been derived from its n. m. r. spectrum.

The structure (III) reported by Lappin (2) for the diadducts formed by the reaction of methyl propiolate with 2-aminopyridines has been found to be incorrect. The correct structure (IV) has been proven by spectral studies and cyclisation to compound VII. In two cases new compounds having structures of the type (III) have been isolated. N.M.R. data are reported for all products.

In the cycloaddition reaction of isoquinolinium bis (methoxycarbonyl) methylide (VI) and isoquinolinium cyano (methoxycarbonyl) methylide (VIII) with methyl propiolate (II), the primary adducts, trimethyl-3, 10b-dihydropyrrolo [2, 1-α] isoquinoline-1, 3, 3-tricarboxylate (VII) and dimethyl 3-cyano 3, 10b-dihydropyrrolo [2, 1-α] isoquinoline-1, 3-dicarboxylate (IX), were isolated. The stability of the primary adduct was found to be affected by the kind of substituent at 3-position.

not available

Die tetrasubstituierten [2.2]Paracyclophane 4a – e werden durch Cycloaddition der symmetrischen Acetylenderivate 2a – e an 1,2,4,5-Hexatetraen (1) dargestellt und ihre Konstitution und Konfiguration durch spektroskopische Methoden. Abbau- und Pyrolyseversuche bewiesen. Der Tetramethylester 4a wird zum Tetraalkohol 4g reduziert und die Tetracarbonsaure 4c in das Bisanhydrid 4f bzw. [2.2] Paracyclophan (4h) ubergefuhrt. Bei der Anlagerung von Propiolsaure-methylester (5a) an 1 werden alle isomeren disubstituierten [2.2]paracyclophanes 6 erhalten. Weitere symmetrische und unsymmetrische Acetylenderivate reagieren nicht mit 1. Preparation of [2.2]Paracyclophanes by Addition of Acetylene Derivatives to 1,2,4,5-Hexatetraene The tetrasubstituted [2.2]paracyclophanes 4a – e are formed by cycloaddition of the symmetrical acetylene derivatives 2a – e to 1,2,4,5-hexatetraene (1), and their constitution and configuration is established by spectroscopic methods, degradation and pyrolysis experiments. The tetramethyl ester 4a is reduced to the tetraalcohol 4g, and the tetracarboxylic acid 4c is converted to the bisanhydride 4f and [2.2] paracyclophanes (4h), respectively. All possible disubstituted [2.2] paracyclophanes 6 are obtained when methyl propiolate (5a) is added to. 1, whereas further symmetrical and unsymmetrical acetylene derivatives do not react with 1.

Synthesis and structure of novel ylidic thiabenzenes, 1-cyano-and benzoyl-2-methyl-2-thianaphthalenes (VI and X), are discussed. The reactions of VI with several electrophiles such as dimethyl acetylenedicarboxylate, methyl propiolate, diphenylcyclopropenethione, and diphenylcyclopropene are described together with the mechanisms of the reactions.

The synthesis of methyl 4,7-anhydro-5,6,8-tri-O-benzyl-2,3-dideoxy-D-allo-oct-2-ynoate (2) and its D-altro isomer (5) is reported; the ester (5) reacts with benzyl azide to give two isomeric triazoles (10) and (11).

The reaction of methyl (2-pyridyl)acetate with methyl propiolate gave quinolizine derivatives; (2-pyridyl)acetone and 1-(2-pyridyl)butan-2-one reacted similarly. 2-Acetylpyridine and ethyl pyridine-2-carboxylate reacted with methyl propiolate to yield pyrrolo[2,1,5-cd]indolizines. The structures of the products were deduced mainly from their u.v. and n.m.r. spectra.

[1-Alkylpyridin-4(1H)-ylidene] acetates and related compounds react at the exocyclic double bond with electrophilic acetylenes to give 1 : 1 and 1 : 2 adducts by simple Michael addition followed by proton shift. With tetracyanoethylene a related product was isolated and also a compound in which the ester group had been lost. Methyl [1-alkylpyridin-2(1H)-ylidene] acetates give analogous products with methyl propiolate, but-3-yn-2-one, and 4-phenylbut-3-yn-2-one.

The synthesis of 1,4-dihydropyridines unsubstituted in the 1-, 2-, and 6-positions from methyl propiolate, aromatic aldehydes, and ammonium acetate in acetic acid is described. The products were oxidised to the corresponding pyridines. Certain features of their n.m.r. spectra are discussed.

Denydrobromination of 2-styrylpyridine (stilbazole) dibromide with potassium t-butoxide yielded 2-phenylethy pyridine, which with dimethyl acetylenedicarboxylate gave tetramethyl oxybis-1-phenylmethylene-indolizine-2,3-dicarboxylate. The products from reaction of the acetylene with 2-styrylpyridine dibromide, 2(1H)-pyridylmethyleacetophenone, and α-(2-pyridyl)acetophenone, and from reaction of methyl propiolate with α-(2-pyridyl)acetophenone, were identified.

Isoquinolinium ylides react with dimethyl acetylenedicarboxylate to yield 2,3-dihydrobenzo[g]-indolizines and the corresponding benzo[g]indolizines, whilst with methyl propiolate only the latter are obtained.

The predominant mode of 1,3-dipolar addition of 2-diazopropane to methyl but-2-ynoate is the opposite of that predicted on electronic grounds, 4-methoxycarbonyl-3,3,5-trimethyl-3H-pyrazole and 5-methoxycarbonyl-3,3,4-trimethyl-3H-pyrazole being obtained in the ratio 6 : 1. In contrast, methyl propiolate behaves normally with 2-diazopropane, giving solely 3,3-dimethyl-5-methoxycarbonyl-3H-pyrazole. The preference for reverse addition to methyl but-2-ynoate is attributed to steric factors in the transition states for cycloaddition.The structures of the 3H-pyrazoles were established by photolysis, the diazoalkenes initially generated being trapped with acetic acid as acetoxy-esters. In the absence of acetic acid, the diazo-intermediates underwent further photolysis to cyclopropenes.

Non-terminal acetylenic esters react with many thiocarbonyl compounds to form heterocycles or 1 : 1 addition products. Propiolic esters in most cases form isomeric mixtures of dimethyl 3,3′-thiodiacrylates (I). The stereochemical course of the thiolic nucleophilic additions may be controlled for preparative purposes by changes in solvent polarity. All three stereoisomers of (I) have been prepared. The trans-isomer of methyl 3-(1,1-dimethyl-3-phenyl-2-isothioureido)acrylate, unlike the cis-, undergoes complete rearrangement to the tetrasubstituted thiourea.

Reactions of methyl propiolate with benzimidazole and its 2-alkyl and aryl derivatives, in acetonitrile, gave the corresponding methyl 3-trans-(benzimidazol-1-yl)acrylates, whereas a reaction with benzimidazole in methanol gave the cis-isomer exclusively. Similar acrylates were formed from methyl tetrolate and methyl phenylpropiolate. Other products were pyrrolo[1,2-a]quinoxalines and a pyrrolo[1,2-a]benzimidazole.

Benzimidazole-2-acetonitrile, ethyl benzimidazole-2-acetate, and their 1-methyl derivatives were heated with methyl propiolate and with dimethyl acetylenedicarboxylate in acetonitrile. The resulting mixtures, on chromatography gave pyrrolo-, pyrido-, and azepino-[1,2-a]benzimidazoles, the structures of which were deduced from their spectral properties.

3,5-Dimethylpyridine and methyl propiolate gave methyl [1,2-dihydro-1-(trans-2-methoxycarbonylvinyl)-3,5-dimethyl-2-pyridyl]propiolate. Addition of methanol to the reaction media, as with other pyridines, gave the corresponding 1,2-dihydro-2-methoxy-1-(methoxycarbonylvinyl)pyridines, whereas addition of water yielded dihydropyridines with a divinyl ether side-chain. Addition of phenol gave only phenoxyacrylates. Ethyl 3-(2-pyridyl)-trans-acrylate with acetylenic mono- and di-esters gave 4H-quinolizines via a spiro-intermediate, with the apparent migration of an ester group.

A series of dibenzophosphorin oxides has been prepared by ring expansion of dibenzophosph(III)oles with methyl propiolate. The structures of the oxides have been confirmed by independent synthesis. Ring expansion occurs to a considerable extent even when the phosphorus atom bears a benzyl group. The n.m.r. spectra of dibenzophosphorin oxides are discussed.

Pyridine and its 3- and 4-methyl- and 3,5-dimethyl-derivatives with methyl propiolate gave indolizines and cycl-[3,2,2]azine esters, identified largely from their mass, n.m.r., and u.v. spectra. The formation of these products is discussed. The cyclazine from pyridine has been degraded to 1-methylcycl[3,2,2]azine, the n.m.r. spectrum of which has been fully analysed. 4-Methylpyridine also gave 1,4-dihydro-1-(2-methoxycarbonyl-trans-vinyl)-4-(3-methoxycarbonylprop-2-enylidene)pyridine.

Reactions of some quinolines, isoquinolines, and phenanthridines with methyl propiolate have been investigated; the structures of the products, usually benzoindolizines, have been deduced from their u.v., n.m.r., and mass spectra.