Phenylpropiolate esters

IV-Substituted derivatives have been prepared by the reaction of IV-methylhydroxylamine with phenylpropiolic esters or acid chlorides (71CPB1389), the cyclization of A"-substituted /3-ketohydroxamic acids or the reaction of phenylhydroxylamine with diketene (Scheme 150) 63GEP1146494). 

The azomethine ylid 53, generated thermally from the aziridine 52, underwent cycloaddition in near quantitative yield. With DMAD, only one product is possible with EP the sole product was 54, and EPP gave 54 and 55 in 80 20 ratio. This latter result indicates that steric effects are important with the phenylpropiolic ester.52 Nitrones (57) add to benzylideneacenaphthenone (56) forming the spiroisoxazolidines (58), which lose aldehyde fragments on heating or photolysis to give the... 

Russian workers102 first added pyrrolidine to propiolic, tetrolic, and phenylpropiolic esters. Later,103-105 such Michael additions were carried out in various solvents. With MP, pyrrolidine gave the trans adduct 65, whereas DMAD gave a mixture of maleate (66) and fumarate (67) esters. Akerblom106,107 has described similar additions of pyrrolidine to the furyl (68) and phenylpropiolic esters. 

The mesoionic pyrimidine 243349 (from carbon suboxide and 4,6-dimethyl-2-methylaminopyrimidine) added DMAD (and dicyanoacetyl-ene and 1,3-diphenyl- l-oxoprop-2-yne) in boiling xylene giving a good yield of the pyrido[l,2-a]pyrimidin-6-one (245). Phenylpropiolic ester and EP merely converted 243 back into 4,6-dimethyl-2-methylaminopy-rimidine. The fused pyrimidine 247, obtained from benzimidazole (246)... 

Phenylpropiolic ester with l-hydrazino-3-methylisoquinoline gave... 

Sydnones behave as 1,3-dipolar systems and undergo addition reactions with various dipolarophiles. Huisgen, Grashey, Gotthardt, and Schmidt503,504 were the first to react acetylenic esters with sydnones and obtained pyrazoles e.g., 71 with DMAD (1 hour, 120°, in xylene) gave 99% of the pyrazole 73. These reactions have also been carried out with propiolic and phenylpropiolic esters, and their kinetics have been studied.505... 

Almost simultaneously, papers by Schmid et al.509 and by Gotthardt and Reiter510 appeared on the photoaddition of DMAD to sydnones the last authors also used propiolic and phenylpropiolic esters. Ohta et al.511 showed that similar reactions could be carried out with 3-alkyl-4-phenylsydnones, and other papers on the addition of acetylenic esters to sydnones have appeared.512-514... 

Ollis, and Ramsden520 treated 99, 100 and 101 with neat EPP and obtained the pyrazole 103 and the phenylpropiolic ester dimer 104, but no 105. A comparative study was carried out with phenylacetylene. When 100 was heated with DM AD in dioxane, 25% of the pyrazole 106 was obtained. These authors have concluded that the cycloaddition of alkynes to isosydnones is analogous to that of sydnones but the reactions are slower and the cycloadducts are obtained in lower yields. 

In a series of papers under the rubric of Intramolecular Diels-Alder Reactions during 1963-1976, the cyclization inter alia of phenylpropargyl phenylpropiolate esters, i.e., functionality designed to produce arylnaphthalene lactones essentially in one step, was extensively examined (105). With the aryl rings differently substituted by the common substituents, there is little regioselectivity in the cyclization step. A... 

There are few reports in the literature for the synthesis of 3-pyrrolin-2-ones so a simple method for the preparation of substituted 4-phenyl derivatives from phenylpropiolic ester, dimethyl sulphoxonium methylide and amines is welcome (Scheme 64). T-Azaspiroannelation has been described by Bryson and Wilson, ... 

Similarly, methyl propiolate and methyl phenylpropiolate give the cyclazine (67) and its 2-phenyl derivative, respectively, as would be expected of reactions initiated through a Michael addition to the acetylenic ester. 

The ionization of benzoic acids in water at 25° was used by Hammett as the standard reaction for the original qp treatment (2a). This reaction and several analogous reactions, e.g., ionization and ester saponification rates of benzoic acids, cinnamic acids, and phenylpropiolic acids, gives ap correlations of relatively high precision. Taft and Lewis classified such reactions in an A category (2f). Reexamination of these A reactions, as well as additional analogous data which have become available subsequently, provided eight reaction series of data of apparently comparable reliability. In the para position, each of these sets of data meets the necessary condition of a minimal basis set... 

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. 

Other unsaturated esters include cinnamates [68,69] and phenylpropiolates (triple bond) [70], Esters with allenic functionality like 58 have been reported to afford the ortho product 59 in 4% yield (Scheme 22) [71],... 

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... 

Carbanions derived from substances containing active methylene groups are known to react with acetylenic esters leading to heterocyclic compounds. Deoxybenzoins, for example, react with phenylpropiolates... 

Phenyl-3-methyl-5-pyrazolone, 998 p-Phenylpl lenacy 1 bromide, 962 p-Phenylphenacyl esters, 363 Phenylpropiolic acid, 755, 776 Phenylpropionaldehyde, 906, 907 Phenyl propionate, 676... 

Similarly, cyclization of 3-amino-l, 2,4-triazoles (65) with methyl propio-late or methyl phenylpropiolate gave a mixture of the l,2,4-triazolo[4,3-a]pyrimidin-7-ones 97 and the l,2,4-triazolo[l,5-a]pyrimidin-7-ones 98 (70CB3266 71CB2702). In addition, methyl tram-3-(3-amino-l,2,4-triazol-l-yl)acrylates (99) were also obtained. Production of the 1,2,4-triazolopy-rimidines 97 and 98 started by condensation of the ester function with the amino group of 65, followed by cycloaddition of the triazole N4 or N1 of the two tautomeric intermediates 96a and 96b, respectively, onto the carbon-carbon triple bond of the side chain. In contrast, formation of the triazolyl acrylates 99 took place through addition only of the triazole N1 onto the propiolate carbon-carbon triple bond. The relative amounts of products were found to depend on the reaction conditions (temperature, solvent, and time) (70CB3266) (Scheme 42). 

Huisgen and co-workers486,490 have described a useful synthesis of N-substituted pyrroles (41) from mesoionic oxazolones (39) via the intermediates 40, which were not isolated. A variety of acetylenic esters (phenylpropiolic, propiolic, tetrolic, and DMAD) were used. The kinetics of these reactions have been studied.491 The addition of carbon... 

Factors influencing orientation in the condensation of 57 with dipolarophiles were examined by employing ethyl tetrolate in place of the phenylpropiolate. A clean reaction was not obtained, but eventually 60 was isolated indicating that the sterically less demanding ester still adds in the same manner. 

The Michael-type addition of morpholine to propiolic, tetrolic, phenylpropiolic, and acetylenedicarboxylic esters has been described by Postovskii et al.500... 

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