Methyl benzoate, reaction

Mix 31 g. (29-5 ml.) of benzyl alcohol (Section IV, 123 and Section IV,200) and 45 g. (43 ml.) of glacial acetic acid in a 500 ml. round-bottomed flask introduce 1 ml. of concentrated sulphuric acid and a few fragments of porous pot. Attach a reflux condenser to the flask and boil the mixture gently for 9 hours. Pour the reaction mixture into about 200 ml. of water contained in a separatory funnel, add 10 ml. of carbon tetrachloride (to eliminate emulsion formation owing to the slight difference in density of the ester and water, compare Methyl Benzoate, Section IV,176) and shake. Separate the lower layer (solution of benzyl acetate in carbon tetrachloride) and discard the upper aqueous layer. Return the lower layer to the funnel, and wash it successively with water, concentrated sodium bicarbonate solution (until effervescence ceases) and water. Dry over 5 g. of anhydrous magnesium sulphate, and distil under normal pressure (Fig. II, 13, 2) with the aid of an air bath (Fig. II, 5, 3). Collect the benzyl acetate a (colourless liquid) at 213-215°. The yield is 16 g. 

Methylpyrazine reacts with sodamide in liquid ammonia to generate the anion, which may be alkylated to give higher alkylpyrazines (Scheme 10) (61JOC3379). The alkylpyrazines have found extensive use as fiavouring and aroma agents (see Section 2.14.4). Condensation reactions with esters, aldehydes and ketones are common, e.g. methyl benzoate yields phenacylpyrazine in 95% yield, and reactions of this type are summarized in Scheme 11. 

The reaction of the dilithio salt (597) with methyl benzoate and subsequent acid hydrolysis yielded 3-phenyl-4,5,6,7-tetrahydro-2,1-benzisoxazole (598) (76JPS1408). The oxime (599) was converted into (600) by treatment with ethanolic HCl (75JCS(P1)1959>. 

Alkali metal alkoxides, r-butyl acetate neat, 45°, 30 min, 98% yield of r-butyl ester from methyl benzoate. The rate constant for the reaction increases with increasing ionic radius of the metal and with decreasing polarity of the solvent. Equilibrium for the reaction is achieved in <10 sec. Other examples eire presented. " ... 

Evidence in support of the mechanism shown in figure 21.4 comes from isotope-labeling experiments. When 180-labeled methanol reacts with benzoic acid, the methyl benzoate produced is found to be l80-labeled but the water produced is uniabeled. Thus, it is the C-OH bond of the carboxylic acid that is broken during the reaction rather than the CO—H bond and the RO-H bond of the alcohol that is broken rather than the R-OH bond. 

When ethyl benzoate is heated in methanol containing a small amount of HCl, methyl benzoate is formed. Propose a mechanism for the reaction. 

This method was later adapted for the large-scale preparation of the LTD4 antagonist 64 by another Merck Process Research group (Figure 3.11) [21], Conversion of a methyl benzoate to the corresponding acetophenone was required. Formation of the tertiary alcohol was again minimized with the addition of H M DS and excellent reaction performance was achieved. 

The authors chose pyruvic acid as their model compound this C3 molecule plays a central role in the metabolism of living cells. It was recently synthesized for the first time under hydrothermal conditions (Cody et al., 2000). Hazen and Deamer carried out their experiments at pressures and temperatures similar to those in hydrothermal systems (but not chosen to simulate such systems). The non-enzymatic reactions, which took place in relatively concentrated aqueous solutions, were intended to identify the subsequent self-selection and self-organisation potential of prebiotic molecular species. A considerable series of complex organic molecules was tentatively identified, such as methoxy- or methyl-substituted methyl benzoates or 2, 3, 4-trimethyl-2-cyclopenten-l-one, to name only a few. In particular, polymerisation products of pyruvic acid, and products of consecutive reactions such as decarboxylation and cycloaddition, were observed the expected tar fraction was not found, but water-soluble components were found as well as a chloroform-soluble fraction. The latter showed similarities to chloroform-soluble compounds from the Murchison carbonaceous chondrite (Hazen and Deamer, 2007). 

As would be expected, the slopes are almost identical the intercept difference shows that methyl benzoate reacts about 1.5 times as fast as does ethyl benzoate in the standard state, a result easily attributable to the slight increase in steric crowding to the equation (42) hydrolysis in the latter case. The order of the A2 ester hydrolysis reaction in water is thus two, a result quite difficult to obtain in other ways, even in dilute solution, perhaps requiring a proton inventory study of a reaction that is very slow in water. 

Fig. 11 Excess acidity plot against X for the hydrolyses of some esters in aqueous H2S04 at 25°C for methyl benzoate (closed circles), data from ref. 41, and for ethyl benzoate (open circles), data from ref. 210, showing the reaction with two water molecules. PCT, protonation correction term.

Triphenylcarbinol has been obtained by the reaction between phenylmagnesium bromide and benzophenone,1 methyl benzoate, or phosgene 8 by action of phenylsodium upon benzophenone, benzoyl chloride, ethyl chlorocarbonate, or ethyl benzoate 4 by hydrolysis of triphenylchloromethane 5 and by oxidation of tri-phenylmethane.6... 

Although the reaction with thiosulfate and with iodide ions may be a mere reduction of the halide, the reaction with sodium benzoate would appear to be a radical dissociation induced by the attack of a negative ion. The fate of the benzoate ion is unknown. Tris-( -nitrophenyl)-methyl benzoate is a stable substance which does not dissociate into radicals.23... 

Differentiation between the secondary hydroxyl groups in methyl 4,6-O-benzylidene-a-D-glucopyranoside was observed on reaction with methyl benzoate-sodium methoxide at 200° for 45 minutes the 2- and 3-esters and the 2,3-diester were formed176 in the molar ratios of 55 23 10. 

The use of ester and formyl groups for this reaction is also possible. The reaction of methyl benzoates with olefins proceeds when the benzoates have electron-withdrawing substituents such as trifluoromethyl, cyano, and ester groups (Equation (8)).5,5a In the case of aldehydes, the reaction requires sterically hindered substituents such as tert-butyl and trimethylsilyl groups.6... 

These authors also reported that /V-acyloxy-/V-alkoxyamides did not undergo methanolysis under the same conditions but treatment of /V-acctoxy-/V-ethoxybenz-amide 25a in more forcing conditions with NaOMe in DME afforded a mixture of ethyl and methylbenzoate, 97 and 98 (Scheme 20). They attributed the formation of the former to a HERON reaction and methyl benzoate to the direct attack of methoxide at the amide carbonyl. 

Method B - with NafTe. A mixture of Te (0.64 g, 5 mmol) and NaBH4 (0.45 g 12 mmol) in DME (20 mL) is heated at 80-90°C under N2 for 30 min, giving an almost colourless suspension (which has been proved to be Na2Te by reaction with 1-bromobntane to give dibntyl telluride). Methyl benzoate is added, and after heating at 80-90°C for 20 min the mixtnre is worked up as for method A, giving pnre benzoic acid (0.99 g (90%) m.p. 121-122°C). 

Amines also react with esters by a method similar to the reaction of an acid chloride with an cimine (which was described in the previous section, From acid chlorides ). Figure 12-28 illustrates the formation of benzamide by this type of reaction, using ammonia and methyl benzoate. Again, the mechanism is similar to the reaction of an acid chloride with an amine (Figure 12-26). 

There is one report of competitive nucleophilic attack at the amide carbonyl in an Ai-acyloxy-A-aUtoxyamide. Shtamburg and coworkers have reported that MeONa reacted with Ai-acetoxy-A-ethoxybenzamide (159) in DME giving methyl and ethyl benzoate (160 and 161) (Scheme 26) . They attributed the formation of methyl benzoate to the direct attack of methoxide ion at the amide carbonyl rather than at nitrogen. The formation of 161 was attributed to a HERON reaction. Though not mentioned by the authors, it seems likely that under these aprotic conditions, 162 could also have been formed by methoxide attack at the acetate carbonyl leading to an anion-induced HERON reaction, by analogy with the reaction of Ai-acyloxy-Ai-alkoxyamides and aqueous hydroxide discussed above (Section IV.C.3.c)... 

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