Ethyl phenylpropiolate, reaction with

General methods for preparation of imidazolidin-4-one-2-thiones include the reaction of thioureas with a-dicarbonyl compounds, with ethyl phenylpropiolate, and with phenyl chlorothiolacetate, and cyclization in acid of l-(carbethoxymethyl)-2-thioureas. The analogous reaction of a-dicarbonyl compounds with selenoureas produce imidazolidin-4-one-2-selones. Berlin and Levi utilized the acid-catalyzed cyclization of l-aryl-3-carbalkoxymethyl-2-thioureas to produce 3-arylimidazolidin-4-onc-2-thiones (23). 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Although the reaction of certain acetylenes such as phenylacetylene and ethyl phenylpropiolate with cold concentrated sulfuric acid to give acetophenone (15) and benzoylacetic acid (16) has been known since the 1880 s, it was only in the 1960 s that this reaction was studied mechanistically. 

The reaction of triphenylphosphine hydrobromide with phenylpropiolic acid gives a mixture of the )- and (Z)-isomers of 2-carboxy-l-phenyl-vinyltriphenylphosphonium bromide (67), not just the (Z)-isomer as previously reported. ( )-2-Ethoxycarbonyl-l-phenylvinyltriphenylphos-phonium bromide (68) can be prepared in a similar reaction from ethyl phenylpropiolate. 

A. Preparation.—The first reverse Wittig olefin synthesis has been reported. Triphenylphosphine oxide and dicyanoacetylene at 160 °C gave the stable ylide (1 78%) the reaction was reversed at 300 °C. No comparable reaction was observed with a variety of other activated acetylenes but tri phenyl arsine oxide gave the corresponding stable arsoranes with dicyanoacetylene (— 70 °C), methyl propiolate, hexafluorobut-2-yne, dimethyl acetylene dicarboxylate, and ethyl phenylpropiolate (130 °C). 

The reactions of heteroaromatic compounds such as furans, pyrroles, and indoles with alkynoates proceed under very mild conditions (in acetic acid or even in neutral solvents such as CH2C12 at room temperature). For example, the reaction of pyrrole with ethyl phenylpropiolate gives the 2-alkenylated pyrrole (Equation (44)).47c This reaction is applied to the direct synthesis of a /3-alkenylpyrrole, the pyrrole fragment of haemin (Equation (45)).47d The present reaction provides a very convenient method for functionalization of arenes and heteroarenes. 

The intermolecular reaction of phenols with propiolic esters occurs in the presence of a Pd(OAc)2 catalyst to afford coumarin derivatives directly.48,48a An exclusive formation of 5,6,7-trimethoxy-4-phenylcoumarin is observed in the Pd(OAc)2-catalyzed reaction of 3,4,5-trimethoxyphenol with ethyl phenylpropiolate in TFA (Equation (46)). Coumarin derivatives are obtained in high yields in the cases of electron-rich phenols, such as 3,4-methylenedioxyphenol, 3-methoxyphenol, 2-naphthol, and 3,5-dimethylphenol. A similar direct route to coumarin derivatives is accomplished by the reaction of phenols with propiolic acids (Equation (47)).49 A similar reaction proceeds in formic acid at room temperature for the synthesis of coumarins.50,50a Interestingly, Pd(0), rather than Pd(n), is involved in this reaction. 

Substituted acetophenones react with ethyl phenylpropiolate under the conditions of the Michael reaction to give pyrones. Formulate a mechanism. 

The reaction of aroylhydrazines with DMAD gives rise to the hydrazones of oxaloacetic ester, which undergo thermal transformation to the corresponding diaroylhydrazines. b. Hydrazones. Ethyl l,3,5-triphenylpyrazole-4-carboxylate has been reported to be formed in the reaction of benzaldehyde phenylhydrazone with ethyl phenylpropiolate. In a detailed investigation, George and co-workers have shown that aldehyde phenylhydrazones react with DMAD, yielding a mixture of pyrazoles and pyrazolines. Thus, in the reaction of benzaldehyde phenylhydrazone with DMAD, products such as dimethyl l,3-diphenylpyrazoline-4,5-dicarboxylate (129), dimethyl... 

The reaction of arylacetamides with ethyl phenylpropiolate gives 4,5-diaryl-l,5-dihydro-2//,67/-pyridine-2,6-diones (197). - It has been suggested that the pyridinediones in these reactions are formed through the initial addition of either the amide anion (195) or the carbanion (196), generated under basic conditions, to ethyl phenylpropiolate (Scheme 30). 

In the reversible Wittig reaction, triphenylarsine oxide reacted with electron-deficient acetylene derivatives to form stable ylides. Thus triphenylarsine oxide reacted readily with methyl propiolate, ethyl phenylpropiolate, dimethyl acetylenedicarboxylate, and hexafluoro-2-butyne as well as dicyanoacetylene to give arsonium ylides (12). The reaction temperatures required ranged from -70°C in the case of dicyanoacetylene to 130°C in the case of ethyl phenylpropiolate (15). 

Isotope experiments revealed that D-atoms were incorporated to the vinyl position of adducts either in inter- or intramolecular reactions in d-TFA (Scheme 5) [3b, c]. Reaction of heteroarenes with alkynoates in AcOD gave similar results [4]. Also, addition of heteroaromatic C-D bonds to the C-C multiple bonds and the large isotope effect k,HlkD = 3) between pyrrole and ds-pyrrole in the reaction with ethyl phenylpropiolate were observed. 

Pd(ll)-catalyzed Reaction of 3,4,5-Trimethoxyphenol with Ethyl Phenylpropiolate. 5,6,7-Trimethoxy-4-phenylcoumarin... 

The reaction with triphenylphosphine oxide cannot be extended to other negatively substituted acetylenes. However, the reaction with triphenylarsine oxide proceeds much more readily, and this reagent reacts with methyl propiolate, dimethyl acetylene-dicarboxylate, ethyl phenylpropiolate, and hexafiuoro-2-butyne to give products (2) in good yield (55-90%). 

In the case of a,/3-unsaturated esters, Michael addition and Claisen condensation are liable to proceed simultaneously. Equation 108 shows one of these cases where ethyl phenylpropiolate (123) reacted with dibenzyl ketone (124) by a combination of both types of reactions, leading to the formation of 2,4,5-triphenylresorcinol (125) . 

Acetylenic carboxylic acids are relatively easily accessible. Acetylenedicarb-oxylic acid is prepared from dibromosuccinic acid by reaction with methanolic potassium hydroxide solution.183 Phenylpropiolic acid can be prepared by the action of the same reagent on ethyl, / -dibromocinnamate and treatment of the resulting potassium salt with dilute sulfuric acid 184... 

It is of interest that the pyridine (17) can be synthesised by intramolecular Diels-Alder reaction of (16) since 2-arylisoxazoles are not useful components in intermolecular Diels-Alder reactions Ketimines react with acrylamide and methylacrylamide in the presence of aluminium chloride to afford 2-oxotetrahydropyridines by a C - alkylation pathwayJ34 however 4-oxopyridines result from the reaction of ketimines with ethyl phenylpropiolate using the same catalyst (Scheme 4).35... 

The reaction of pyridinium iV-dicyanomethylide 223 with ethyl phenylpropiolate 224 (R = C02Et), under solvent-free conditions using MWI afforded a mixture of the two possible regjoisomers 225 and 227. Reaction was performed in a monomode reactor in order to have an accurate control of temperature to prevent the decomposition of 223. The best results (84-87%) were obtained using a molar ratio of ylide dipolarophile 1 1.5 or 1.5 1 and irradiation at 120 W over 25 min at 150°C (Scheme 48). Yields were increased from 61% to 87% when compared with conventional heating. Reactions in the presence of different supports were performed under MWI the best selectivity was obtained using neutral bentonite or silica gel. 

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