Phenyl acetate ester

Phenyl-ethyl alcohol can be prepared by numerous methods, several of which are the subject-matter of patents. It may be prepared, for example, by the conversion of phenyl-bromo-lactic acid into phenyl-acetaldehyde, and then reducing this body with sodium. Or it may be prepared by reducing phenyl-acetic esters with sodium and absolute alcohol in the folio-wing manner —... 

Method F The haloalkane (0.25 mmol) is added to the Cr(CO),-complex of the phenyl-acetic ester (0.25 mmol) in CH2CI2 (5 ml) and CTA-Br (36 mg, 0.1 mmol) in aqueous NaOH (50%, 5 ml). The mixture is stirred at room temperature until the reaction is complete, as indicated by TLC analysis, and the organic phase is then separated, washed well with water, dried (Na2S04), and evaporated to yield the C-alkylated derivative (70-100%). 

The phenyl acetic acid esters are highly valuable intermediates for a lot of applications. Among them, they are applied for the synthesis of fragrances e.g. ethyl ester (honey odour), isobutyl ester (sweet roses odour). The present industrial process for phenyl acetic esters starts from benzylchloride and uses the reactions with KCN to form benzylcyanide 7 (Eq. 15.2.4) and followed by hydrolytic cleavage. 

Another important research direction is the mimieking of enzymes and the construction of selective catalysts. For these purposes, the polymer is imprinted with the desired reaetion-product or better, a molecule which resembles the transition state of the reaction adducts. If the educts bind specifically to the recognition site, they become confined into these micro-reactors and are supposed to react faster and more defined than outside the cavities [445]. Examples for reactions in the presence of such synthetic enzymes can be found in [452,453,454,455,456,457] (cf Figure 40c). First positive results have been reported, e.g. an synthetic esterase , increasing the rate of alkaline hydrolysis of substituted phenyl-(2-(4-carboxy-phenyl)-acetic esters for 80 times [488] and Diels-Alder catalysis fiuic-tional holes containing titanium lewis-acids [489]... 

Group or atom substitutions for hydrogens at the C-1, C-a, and C-)S positions all effect reaction rates. However, the rates are most sensitive to substitutions at the C-a position. This is readily apparent from an examination of the rate coefiBcients in Table 1 (Column 3). With the exception of the 8-phenyl acetate esters, all primary esters have rate coefficients in the range of log k (600 °K) = —5.0 0.5. Note also that corrected activation energies are in the range of (primary) =... 

The rate constants for reaction of phenolate ion and 4-cyanophenolate ion with substituted phenyl acetate esters are given in Table 1 ... 

Increasing the temperature to 350 °C results in decarbonylation of the phenylpyruvic acid methyl ester derivatives and the phenyl acetic ester is formed with a ratio of 65 % a-ketoester to 35 % acetic acid ester. Until now the industrial process for the synthesis of phenylacetic acid ester has started from benzyl chloride, which is converted to benzyl cyanide by KCN, followed by hydrolysis. Every step of this reaction must be performed in a separate reactor and special measures must be taken for handling large amounts of toxic KCN. The new route is certainly an environmentally benign alternative [8,27]. 

Very recently, it has been demonstrated [76] that the hosts (RR)-(29) and (R)- 59), complexed to KOCMej or KNHj, catalyse the Michael additions of methyl vinyl ketone and methyl acrylate to the phenyl acetic esters (61) and (62), and the )8-ketoester (63) with high catalytic turnover numbers (CTN = mmoles of product... 

D-lyxo-l,2,3-trihydroxybutyl)-p-D-xylopyranosid-4-yl)-2-phenyl-, hexaacetate ester -4-methanol, a-t5-(acetyloxy)-l,3-doxan-4-yl]-2-phenyl-, acetate ester, [4S-[4o(S ), 5a]]--4-methanol, a -(aminometyl)-2-phenyl--4-methanol, 2-(4-bromo-3-chlorophenyl)--4-methanol, 2-(4-bromo-3-methylphenyl)--4-methanol, 2-(4-bromophenyl)--4-methanol, 2-(3-chlorophenyl)--4-methanol, 2-(4-chlorophenyl)--4-methanol, a -(ethylaminomethyl)-2-phenyl--4-methanol, a -(5-hydroxy-1,3-dioxan-4-yl)-2-phenyl-, [4S-[4a(S ), 5o]]-... 

Although the authors did not specifically address the issue of silyl ketene acetal geometry, the stereoselectivity of the silyl ketene acetal in these cases is noteworthy. Ireland had previously shown that phenyl acetic esters gave low E-stereoselec-tivity upon treatment with LDA and TBSCl (vide infra, Section 4.6.1.1). Either LHMDS/TMSCl gives higher f-selectivity in the case of phenyl acetic esters or the Lewis acid may be playing a role in both ketene acetal isomerization as well as rearrangement... 

The ester and catalj st are usually employed in equimoleciilar amounts. With R =CjHs (phenyl propionate), the products are o- and p-propiophenol with R = CH3 (phenyl acetate), o- and p-hydroxyacetophenone are formed. The nature of the product is influenced by the structure of the ester, by the temperature, the solvent and the amount of aluminium chloride used generally, low reaction temperatures favour the formation of p-hydroxy ketones. It is usually possible to separate the two hydroxy ketones by fractional distillation under diminished pressure through an efficient fractionating column or by steam distillation the ortho compounds, being chelated, are more volatile in steam It may be mentioned that Clemmensen reduction (compare Section IV,6) of the hj droxy ketones affords an excellent route to the substituted phenols. 

To hydrolyse an ester of a phenol (e.g., phenyl acetate), proceed as above but cool the alkaline reaction mixture and treat it with carbon dioxide until saturated (sohd carbon dioxide may also be used). Whether a solid phenol separates or not, remove it by extraction with ether. Acidify the aqueous bicarbonate solution with dilute sulphuric acid and isolate the acid as detailed for the ester of an alcohol. An alternative method, which is not so time-consuming, may be employed. Cool the alkaline reaction mixture in ice water, and add dilute sulphuric acid with stirring until the solution is acidic to Congo red paper and the acid, if aromatic or otherwise insoluble in the medium, commences to separate as a faint but permanent precipitate. Now add 5 per cent, sodium carbonate solution with vigorous stirring until the solution is alkaline to litmus paper and the precipitate redissolves completely. Remove the phenol by extraction with ether. Acidify the residual aqueous solution and investigate the organic acid as above. 

However, this method is appHed only when esterification cannot be effected by the usual acid—alcohol reaction because of the higher cost of the anhydrides. The production of cellulose acetate (see Fibers, cellulose esters), phenyl acetate (used in acetaminophen production), and aspirin (acetylsahcyhc acid) (see Salicylic acid) are examples of the large-scale use of acetic anhydride. The speed of acylation is greatiy increased by the use of catalysts (68) such as sulfuric acid, perchloric acid, trifluoroacetic acid, phosphoms pentoxide, 2inc chloride, ferric chloride, sodium acetate, and tertiary amines, eg, 4-dimethylaminopyridine. 

We should distinguish between the phrases nucleophilic attack and nucleophilic catalysis. Nucleophilic attack means the bond-forming approach by an electron pair of the nucleophile to an electron-deficient site on the substrate. In nucleophilic catalysis this results in an increase in the rate of reaction relative to the rate in the absence of the catalyst. However, nucleophilic attack may not result in catalysis. Thus, if methylamine is reacted with a phenyl acetate, the reaction observed is amide formation, not hydrolysis, because the product of the nucleophilic attack is more stable than is the ester to hydrolysis. 

It is obtained by allowing a solution of one molecule of phenol-acetic -ester in three to four times its weight of absolute alcohol, to fall in drops on a quantity of sodium calculated for six atoms. It is then heated for several hours on an oil-bath, until the sodium has disappeared, if necessary adding more alcohol. After cooling, water is added, and the ester which is not attacked is saponified. The alcohol and phenyl-ethyl alcohol are then distilled off with steam, when the latter is at once obtained in the pure state. 

It is suitable, not only for rose odours, but also for blending with almost any flower oil. Phenyl-ethyl alcohol forms a solid compound with chloride of calcium, which is very useful for its purification. On oxidation it is converted into a mixture of phenyl-acetaldehyde and phenyl-acetic acid. The last-named body forms an ethyl ester melting at 28°, which serves for its identification. 

Phenyl-propyl alcohol, CgH. CHj. CH.2. CHj. OH, is the next highest homologue of phenyl-ethyl alcohol, and is also known as hydro-cinnamyl alcohol. Like the last described bodies it has been known for many years, its first preparation being described in the Aivnalen (188, 202). It occurs as a cinnamic acid ester in storax, and as an acetic ester in cassia oil. It is prepared synthetically by the reduction of cinnamyl alcohol with sodium amalgam and water, or by the reduction of cinnamic or benzyl acetic esters with sodium and absolute alcohol. It has the following characters —... 

Shuric acid, yields phenyl-acetic acid or a-toluic acid. This is con-ansed with methyl alcohol, forming the methyl ester of the formula. COOCH3. It has a powerful honey odour, and is very useful in scent bases of this type. 

Ethyl Phenyl-acetate.—This ester has the formula C[Pg.167]

Styrolyl Acetate.—Styrolene alcohol, or phenyl-ethyl glycol, is an alcohol prepared from styrolene dibromide by the action of caustic potash. It can be esterified, and forms an acetic ester of the formula CgHj. CH(OH)CHg. OOC. CHg. It is an ester with a fine flower odour, which has been described as fragrant and dreamy . It is generally stated by those who have used it that it is indispensable in the preparation of fine flower bouquets with a jasmin odour. 

As described in U.S. Patent 2,507,631, 80 g of pulverized sodium amide are gradually added, while stirring and cooling, to a solution of 117 g of phenyl-acetonitrile and 113 g of 2-chloropyridine in 400 cc of absolute toluene. The mixture is then slowly heated to 110° to 120°C and maintained at this temperature for 1 hour. Water is added thereto after cooling, the toluene solution is shaken with dilute hydrochloric acid and the hydrochloric acid extracts are made alkaline with concentrated caustic soda solution. A solid mass is separated thereby which is taken up in acetic ester and distilled, a-phenyl-a-pvridyl-(2)-acetonitrile passing over at 150° to 155°C under 0.5 mm pressure. When re-crystallized from ethyl acetate it melts at 88° to 89°C, the yield amounting to 135 g. 

To a solution of 4 g of sodium in 200 ml of n-propanol is added 39 g of homovanillic acid-n-propyl ester (boiling point 160°C to 162°C/4 mm Hg) and the mixture is concentrated by evaporation under vacuum. After dissolving the residue in 200 ml of dimethylformamide and the addition of 0.5 gof sodium iodide, 26.2 g of chloracetic acid-N,N-diethylamide are added drop-wise with stirring at an internal temperature of 130°C, and the mixture is further heated at 130°C for three hours. From the cooled reaction mixture the precipitated salts are removed by filtering off with suction. After driving off the dimethylformamide under vacuum, the product is fractionated under vacuum, and 44.3 g of 3-methoxy-4-N,N-diethylcarbamido-methoxy phenyl acetic acid-n-propyl ester are obtained as a yellowish oil of boiling point 210°C to 212°C/0,7 mm Hg,... 

In these equations, Dmax is the larger of the summed values of STERIMOL parameters, Bj, for the opposite pair 68). It expresses the maximum total width of substituents. The coefficients of the ct° terms in Eqs. 37 to 39 were virtually equal to that in Eq. 40. This means that the a° terms essentially represent the hydrolytic reactivity of an ester itself and are virtually independent of cyclodextrin catalysis. The catalytic effect of cyclodextrin is only involved in the Dmax term. Interestingly, the coefficient of Draax was negative in Eq. 37 and positive in Eq. 38. This fact indicates that bulky substituents at the meta position are favorable, while those at the para position unfavorable, for the rate acceleration in the (S-cyclodextrin catalysis. Similar results have been obtained for a-cyclodextrin catalysis, but not for (S-cyclodextrin catalysis, by Silipo and Hansch described above. Equation 39 suggests the existence of an optimum diameter for the proper fit of m-substituents in the cavity of a-cyclodextrin. The optimum Dmax value was estimated from Eq. 39 as 4.4 A, which is approximately equivalent to the diameter of the a-cyclodextrin cavity. The situation is shown in Fig. 8. A similar parabolic relationship would be obtained for (5-cyclodextrin catalysis, too, if the correlation analysis involved phenyl acetates with such bulky substituents that they cannot be included within the (5-cyclodextrin cavity. 

Acetic acid, /mhuktiiv laming phenyl-, ETHYL ESTER, 47, 69... 

The enantiomeric excess (ee) of the hydrogenated products was determined either by polarimetry, GLC equipped with a chiral column or H-NMR with a chiral shift reagent. Methyl lactate and methyl 3-hydroxybutanoate, obtained from 1 and 2, respectively, were analized polarimetry using a Perkin-Elmer 243B instrument. The reference values of [a]o(neat) were +8.4° for (R)-methyl pyruvate and -22.95° for methyl 3-hydroxybutcinoate. Before GLC analysis, i-butyl 5-hydroxyhexanoate, methyl 5-hydroxyhexanoate, and n-butyl 5-hydroxyhexanoate, obtained from 1, 5, and 6, respectively, were converted to the pentanoyl esters, methyl 3-hydroxybutanoate was converted to the acetyl ester, and methyl 4-methyl-3-hydroxybutanoate obtained from 2 was converted the ester of (+)-a-methyl-a-(trifluoromethyl)phenyl acetic acid (MTPA). 

Phosphate ester crystal structures have been determined of zinc 1,5,9-triazacyclononane including an interesting structure containing an oligophosphate bridged zinc unit.450 The zinc complex of 1,5,9-triazacyclododecane was studied as a hydrolysis catalyst for substituted phenyl acetates.451 Kinetic analysis suggested that hydrolysis occurs by a mechanism involving hydroxide attack of a metal-bound carbonyl. 

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