Methyl phenylacetate

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%). ... 

Synthesis of pyrazole 3 by the Medicinal Chemistry route was straightforward from N-Boc isonipecotic acid (45), so we utilized the route after some optimizations, as summarized in Table 2.4. The key 1,3-diketone intermediate 48 was prepared from 45 without issues. A minor problem in the original route was the exothermic nature of the Claisen condensation between methyl ketone 47 and methyl phenylacetate. Slow addition of l.lequiv of methyl phenylacetate to a mixture of 47, 0.2equiv of MeOH, and 2.5equiv of NaH in THF at room temperature solved this exothermic issue and reduced the amount of self-condensation of... 

Add 0.44 moles ring substituted phenylacetate, 100 g acetic anhydride and 30 g sodium acetate and heat at 145-150° for 18 hours to get ca. 0.4 moles of the methyl-phenylacetate (I). Add (I) and formamide (or N-methyl-formamide for the N-methyl cpd.), heat 4-5 hours at 180-195°, cool and extract with CHC13. Evaporate in vacuum, dissolve residue in 40% sulfuric acid and heat at 90-125° for 5-6 hours. Neutralize and add solid NaOH to precipitate about 50% amphetamine. Treat with 10% sulfuric acid to get the sulfate. 

Methyl 2-methylbenzoate Methyl 3-methylbenzoate Methyl 4-methylbenzoate Phenyl acetate Benzyl acetate Methyl phenylacetate Ethyl phenylacetate Methyl 3-phenylpropanoate Ethyl 3-phenylpropanoate Methyl 4-phenylbutanoate Dimethyl phthalate Benzonitrile... 

The anion of methyl phenylacetate, formed by an electrogenerated base, was homocoupled with iodine or anodically mediated by iodide to afford dimethyl 2,3-diphenylsuccinate in high yield and high d, /-selectivity. This reaction probably does not involve free radicals but an iodination-nucleophilic substitution sequence [194,195]. 

In order to investigate in more depth the mechanism of Scheme 4.10, a detailed kinetic analysis has been performed by choosing the methylation of phe-nylacetonitrile (2a) and methyl phenylacetate (2b) with DMC as model reactions. Some general considerations are the following. 

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... 

Using this base (Na0Me/A1203) methyl phenylaceteate was obtained in 74 percent yield. Also, other esters, such as isobutyl phenylacetate, could be prepared by reaction in the appropriate solvent (isobutanol, 67 percent yield) using the sodium alkoxide on alumina reagent(45). 

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. 

A recent report( ) on the use of iron carbonyl and potassium carbonate in a similar carboxyalkylation scheme to prepare methyl phenylacetate prompted us to examine the use of carbonate on alumina in a similar manner. It was suggested that if the amount of free base was less than the amount of iron carbonyl than ether formation would not occur being that iron carbonyl was a better electrophile than benzyl halide. Under our conditions, the metal carbonyl anion... 

In the cases where substantial base can be termed extractable-titratable, i.e., methoxide, the deposition onto alumina results in a decrease in concentration of base and an increase in both yield and selectivity to methyl phenylacetate. In the bicarbonate case, the deposition results in an increase in available base and the yield of ester is increased dramatically. 

Fig. 5 b. Polarized spectrum obtained in reaction of 1 (0.2 M) in methyl phenylacetate at 140 Chemical shifts are in hertz downfield from solvent CH3... 

Reductions of keto esters to esters are not very frequent. Both Clemmensen and Wolff-Kizhner reductions can hardly be used. The best way is desulfurization of thioketals with Raney nickel (p. 130). Thus ethyl acetoacetate was reduced to ethyl butyrate in 70% yield, methyl benzoylformate (phenylglyoxy-late) to methyl phenylacetate in 79% yield, and other keto esters gave equally high yields (74-77%) [82J]. 

A related agent, g1icetanile sodiurn (42), is made by a variant of this process. Methyl phenylacetate is reacted with chlorosulfonic acid to give which itself readily reacts with ami nopyrimidine derivative 39 to give sulfonamide Saponification to acid is followed by conversion to the acid chloride and amide formation with 5-chloro-2-methoxyaniline to complete the synthesis of the hypoglycemic agent glicetanile (42). ... 

Our Chemical Development team, under Dr. Chou-Hong Tann, energetically and creatively undertook a vigorous laboratory effort to try to improve the above process to enhance the yield of methyl tropate and also to investigate the reduction of this compound to PPD. Study of the formaldehyde reaction did not quickly yield much improvement, so within weeks and not without overcoming some reluctance to abandon the methyl tropate route, we phased in an exploration of the reaction of methyl formate with methyl phenylacetate, followed by reduction with sodium borohydride. This route almost immediately showed great promise (Scheme 3). 

Honey notes Ethyl phenylacetate Methyl phenylacetate Citronellyl phenylacetate Eugenyl phenylacetate Phenylethyl phenylacetate Phenylacetic acid Cire d abeille absolute... 

Methyl Phenylacetate 150.18/C9H10O2/ colorless or nearly 5—ale, most fixed 1 mL in 6... 

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