Methyl phenylacetate production

Carbocations can also be generated during the electrolysis, and they give rise to alcohols and alkenes. The carbocations are presumably formed by an oxidation of the radical at the electrode before it reacts or diffuses into solution. For example, an investigation of the electrolysis of phenylacetic acid in methanol has led to the identification of benzyl methyl ether (30%), toluene (1%), benzaldehyde dimethylacetal (1%), methyl phenylacetate (6%), and benzyl alcohol (5%), in addition to the coupling product bibenzyl (26%). ... 

Anionicallv Activated Alumina. At this time we had also developed an interest in anionically activated alumina. These basic reagents were active in promoting alkylation(42), condensation(43) and hydrolysis(44) reactions. Thus, we impregnated alumina with sodium hydroxide and used this combination both with and without a phase transfer catalyst (benzyltriethyl ammonium chloride). When BTEAC was added, the conversion to ether was decreased and the formation of ester was noted. In the absence of a phase transfer catalyst, the ether became a minor product and methyl phenylacetate became the major product with coproduction of phenylacetic acid. This ester does not result from esterification of the acid as simple stirring of phenylacetic acid with Na0H/A1203 in methanol does not produce methyl phenylacetate. 

The reaction conditions were mild (room temperature, 1 atm CO) and a two-fold excess of base was used along with a catalytic amount of cobalt carbonyl. The product distribution was quantified by VPC. The mixtures contained starting material, ester product, and various amounts of methyl benzyl ether. No detectable amounts of benzyl alcohol, ketones, or hydrocarbons were seen. Potassium methoxide alone afforded mostly the ether. A mixture of potassium methoxide and alumina gave a slight improvement in ester yield but the predominant product was again the ether. In contrast, when potassium methoxide on alumina was used, the carboxyalkylated product, methyl phenylacetate, was prepared in 70 yield with little ether detected. Benzyl chloride reacted in a similar fashion under these mild reaction conditions. Other alkoxide and carbonate bases could be used as... 

The formation of byproduct methyl benzyl ether was the key reason for the low selectivity to ester in the absence of alumina. A more careful examination of the product distributions with time was made using the alkoxide, alkoxide on alumina and bicarbonate on alumina bases. The results from Table V indicate that the formation of ether was indeed the predominant pathway with alkoxide alone, while the presence of alumina retarded this conversion and promoted the carboxyalkylation pathway. The bicarbonate on alumina gave little ether product and excellent selectivity to the methyl phenylacetate. 

The enolate of methyl phenylacetate adds to a second molecule of methyl phenylacetate to form the Claisen intermediate that is pictured. Elimination of methoxide (circled) and acidification give the product shown. 

AMol reaction. Predominant jyw-aldol products from the reaction of methyl phenylacetate with aldehydes are obtained, in contrast to that promoted by LDA. 

When the analogous rearrangement of dimethyl acetal of a-bromoacetophenone to methyl phenylacetate was attempted under identical experimental conditions as acetals 1 in the presence of ZnETAS, acetophenone (4%) was the most characteristic product formed. In fact, as we have noted above, propiophenone is also formed in detectable amounts starting from acetals 1. 

Palomo JM, Munoz G, Fernandez-Lorente G et al. (2003) Modification of Mucor miehei lipase properties via directed immobilization on different heterofunctional epoxy resins. Hydrolytic resolution of (R,S)-2-butyroyl-2-phenylacetic acid. J Mol Catal B Enzym 21 201-210 Palomo JM, Ortiz C, Fernandez-Lorente G et al. (2005) Lipase-lipase interaction as a new tool to immobilize and modulate the lipase properties. Enzyme Microb Technol 36 447-454 Park EY, Sato M, Kojima S (2006) Fatty acid methyl ester production using Upase-immobilizing silica particles with different particle sizes and different specific surface areas. Enzyme Microb Technol 39(4) 889-896... 

Reaction with Alkynes. Acetals of dihaloacetophenones are prepared from phenylethynes with 7V-halosuccinimide (NIS or NBS) and catalytic amounts of HTIB in methanol (eq 33). When an equimolar quantity of NIS is used in the presence of a catalytic amount of HTIB, a-diiodoacetophenone acetal Is formed in an excellent 3deld. If the ratio of NIS to phenyleth3me Is increased with concomitant increase in the amount of HTIB, the 3deld of the acetal decreases to 7 0% and methyl phenylglyoxylate is formed as a minor product. In this process, there is no evidence of formation of methyl phenylacetate, which is typically formed in the reaction of equimolar HTIB with phenylethjme in hot methanol. The acetal of methyl phenylglyoxylate is also prepared as the sole product by treatment of 2-lodo-l-phenylethyne with NIS and a catalytic amount of HTIB (eq 34). Terminal alkynes are also reported to react with HTIB in an ultrasound enhanced system to furnish arylsulfonates in a quick and simple one-step process (eq 35). ... 

A simple demonstration of the ability of the Cr(CO)3 unit to stabilize a negative charge in the benzylic position is in the alkylation behaviour of methyl phenylacetate (Scheme 10.54). Treatment of the uncom-plexed ester with sodium hydride and 1,3-dibromopropane gave no product as the benzylic protons are not sufficiently acidic to be removed. Under the same conditions, the Cr(CO)3 complex 10.214 gave the expected cyclobutane 10.215. 

This procedure is called chloromethylation and will not only turn 1,3-benzodioxole into a methyl chloride but will work equally well in converting plain old benzene into benzyl chloride. Both are important stepping stones towards the production of X and meth. For example, benzyl chloride is a schedule I controlled substance because it will beget benzaldehyde and phenylacetonitrile (a precursor for phenylacetic acid). 

The method described is successfully used for the alkylation and aralkylation of ethyl and /-butyl phenylacetate.3 The alkylation of ethyl phenylacetate with methyl iodide, M-butyl bromide, benzyl chloride, and a-phenylethyl chloride affords the corresponding pure monoalkylation products in 69%, 91%, 85%, and 70% (erythro isomer) yields, respectively. The alkylation of /-butyl phenylacetate with methyl iodide, M-butyl bromide, a-phenylethyl chloride, and /3-phenylethyl bromide gives the corresponding pure monoalkylated products in 83%, 86%, 72-73%, and 76% yields, respectively. 

Certain of the monoalkylated ethyl phenylacetates have been further alkylated with alkyl and aralkyl halides to produce the corresponding disuhstituted phenylacetic esters.4 Ethyl 2-phenyl-propanoate has been alkylated by methyl iodide to give pure ethyl 2-methyl-2-pheny]propanoate in 81% yield. Similarly, the alkylations of ethyl 2-phenylhexanoate with methyl iodide, M-butyl bromide, and benzyl chloride gave the corresponding pure dialkylated products in 73%, 92%, and 72% yields, respectively. 

Benzenediamine (228) and diethyl dibromomalonate (229) gave ethyl 3-oxo-3,4-dihydro-2-quinoxalinecarboxylate (230) (MeOH, 20°C, 24 h 40%)." The same substrate (228) with ethyl a-bromoisobutyrate gave 3,3-dimethyl-3,4-dihydro-2(17i)-qumoxalinone (231) (Me2NCHO, NEtPr j, 110°C, 7 h 76%) or with methyl 2-bromo-2-phenylacetate gave 3-phenyl-3,4-dihydro-2(l//)-quinoxalinone (232) (KI, K2CO2, AcMe, reflux, 12 h then oily product, MeONa, PhH, reflux, 7 h 89%). ... 

Substituted phenylacetic acids form Kolbe dimers when the phenyl substituents are hydrogen or are electron attracting (Table 2, Nos. 20-23) they yield methyl ethers (non-Kolbe products), when the substituents are electron donating (see also chap. 8). Benzoic acid does not decarboxylate to diphenyl. Here the aromatic nucleus is rather oxidized to a radical cation, that undergoes aromatic substitution with the solvent [145]. 

After evaporation of the solvent the products of reaction are purified by distillation, or, if they are solid, by crystallisation. Use one of the phenols available in the laboratory and report on the nature of the methyl ether obtained. Treat carboxylic acids (p-toluic, phenylacetic, cinnamic, oxalic, terephthalic, salicylic, etc.) in the same way. 

Aryl methyl ketones have been obtained [4, 5] by a modification of the cobalt-catalysed procedure for the synthesis of aryl carboxylic acids (8.3.1). The cobalt tetracarbonyl anion is converted initially by iodomethane into the methyltetra-carbonyl cobalt complex, which reacts with the haloarene (Scheme 8.13). Carboxylic acids are generally obtained as by-products of the reaction and, in several cases, it is the carboxylic acid which predominates. Unlike the carbonylation of haloarenes to produce exclusively the carboxylic acids [6, 7], the reaction does not need photoinitiation. Replacement of the iodomethane with benzyl bromide leads to aryl benzyl ketones in low yield, e.g. 1-bromonaphthalene produces the benzyl ketone (15%), together with the 1-naphthoic acid (5%), phenylacetic acid (15%), 1,2-diphenylethane (15%), dibenzyl ketone (1%), and 56% unchanged starting material [4,5]. a-Bromomethyl ketones dimerize in the presence of cobalt octacarbonyl and... 

In the heretofore reported experiments, as in almost all photo-Fries rearrangements, no weta-rearranged products have been found. Traces of 3-methoxyacetophenone (yield <0.3%) were found upon the irradiation of phenylacetate and after methylation of the reaction mixture.40 Finnegan and... 

Later investigators alcoholyzed imidate salts of other monobasic acids to obtain ortho esters of acetic [13, 14], propionic [15], butyric, valeric, caproic, isocaproic, benzoic [16], and phenylacetic acids [17]. For the latter alcoholysis reactions, the reaction time varies from a few days for the production of methyl orthopropionate to six weeks for ethyl orthobenzoate. McElvain reported that the reaction time is drastically cut by carrying out the reaction in boiling ether [18] or petroleum ether [19]. These conditions provide a reaction temperature below the decomposition point of the imidate salt to the amide. 

Selective carbonylation of HMF was observed to yield 5-formylfuran-2-acetic acid as the sole carbonylation product the only byproduct was 5-methyl-2-furfural (MF). The activity and selectivity were both found to be strongly influenced by the tppts/Pd ratio the maximum efficiency was observed for tppts/Pd = 6. Replacement of tppts by ligands containing fewer sulfonate groups, e.g., tppds or tppms, led to a dramatic drop in the catalytic activity. Furthermore, it was found that the selective carbonylation of benzyl alcohol to phenylacetic acid also took place in the presence of the catalyst (84). 

On HZSM5 both hydroxyacetophenones are formed by trans-acylation. Disproportionation (reaction e) probably does not exist because of steric contraints. Moreover since ortho-hydroxyacetophenone does not react with phenylacetate (probably for the same reason) to give ortho-acetoxyacetophenone, reaction g cannot take place. On the other hand, the formation of products resulting from the oligomerization of ketene (dehydroacetic acid, 6-methyl 4-acetoxy 2-pyrone, reaction h) is favoured presumably because of the confinement effect in the zeolite. These compounds are supposed to be to a large extent responsible for the deactivation of HZSM5. 

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