Methyl 2- benzoate, conversion

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 aryl rings of acetophenone and methyl benzoate are preferentially hydrogenated, with only minor reduction of the substituents. In contrast, hydrogenation of nitrobenzene, under essentially the same conditions, produces aniline and nitro-cyclohexane in ca. 9 1 ratio, with an overall conversion of >79%. This observation has additional significance when compared with the hydrogenation of the nitro derivative of vinylbenzene (Table 11.25). In all cases, it is the C=C bond which is hydrogenated and, only after a prolonged reduction time, is 1-nitro-2-phenylethene completely reduced to the aminoethane [4],... 

The Hammett p-value for cleavage of the exocyclic bond of 2-methoxy-2-substituted-phenyl-l,3-dioxolans (—1.58 + 0.06) is a little larger than that for cleavage of the endocyclic C— bond of 2-hydroxy-2-substituted-phenyl-l,3-dioxolans (—1.24 + 0.04) (Table 9) (Chiang et al., 1983). A direct comparison between the p-values for C—OMe bond cleavage of trimethyl orthobenzoates and dimethyl hemiorthobenzoates is not possible at present since they have not been measured in the same solvent. However, that based on H+ for the breakdown of the hemiorthobenzoates (— 1.58) is less than that based on the equilibrium constants for their conversion into methyl benzoates and methanol which is —1.9 (derived from the equilibrium constants for formation of the hemiorthobenzoates, McClelland and Patel, 1981b). This implies that the development of positive charge in the transition state is less than in the final product, the ester. 

Using isotope dilution analysis Pankratz showed that toluene is indeed the major product at very low conversion (0.016-0.041%), but at higher conversion (0.82-7.75%) the yield of methyl benzoate is as high as 46%, even when photolysis is carried out at 65 K. At 77 K, where thermal collapse of MB to ester is faster, the ratio of ester to toluene increases to 2 1. 

Benzylation of various aromatics with benzyl chloride also proceeds smoothly over 13% Nafion-silica to afford diphenylmethane derivatives in high yields237 (Table 5.18). Although deactivated aromatics (nitrobenzene, methyl benzoate) gave low (< 10%) yields, chlorobenzene reacted readily with complete conversion similar to naphthalene. Furthermore, the catalyst, after recovery, exhibited the same activity. 

Superelectrophilic intermediates have further been proposed in the reactions of some esters. For example, a recent report describes the conversions of methyl benzoate to benzophenone products (70-93% yields) in reactions with superacid (eq 45 ).52... 

Reaction of methyl benzoate (144) with a palladium acetate/heteropolyacid mixture has been studied by Lee and coworkers [98]. They showed that aryl-aryl coupling occurs mainly at the 2-2 positions in the presence of various heteropolyacids (HPA e.g. H3PM012O40, H5PM09V3O40, H5PM010V2O40, etc.) (Scheme 34). The selectivity in favor of the 2-2 coupling product is between 53 and 84 %, but the conversions are low (0.48 to 6.93) due to deactivation of the catalyst. The observed selectivity can be rationalized in terms of formation of the (T-palladium complex 146 with stabilization by the carbonyl group (Figure 3). 

Reduction of substituted benzaldehydes, acetophenones and methyl benzoates has been performed under solvent free conditions (Figure 2.15). Similar solvent free reductions had previously been reported, but these required grinding in a mortar and pestle for 5 days under an inert atmosphere. By performing the reaction in an HSBM, Mack and co-workers were able to perform reactions on an open bench in air and reaction times were reduced to between 1 h and 17h. It should be noted that in one case, the reduction of j9-nitrobenzaldehyde, the reaction was highly exothermic and yields and conversions could not be determined. Therefore, such methods should be used with some caution, as when no solvent is present reactions can suffer from the lack of a heat transfer medium. Importantly, in working up the reactions, only 10% aqueous hydrochloric acid and water were used to quench the reaction and purify the product. If solvent was required to aid purification, the relatively benign VOC methanol was used. 

Direct and selective conversion of esters into ketones, a fundamental reaction but difficult to achieve, has been accomplished by Ahn and co-workers [59] by use of organoaluminum-diamine complexes. The reaction of methyl benzoate with MesAl (3.1 equiv.) and A V -dimethylethylenediamine (DMEDA) (1.1 equiv.) in toluene under reflux followed by an aqueous work-up produced only acetophenone in almost quantitative yield (98 %). Notably, ketones and even aldehydes survive under the reaction conditions. A mechanistic investigation established that the conversion proceeds through transamidation and subsequent intramolecular nucleophilic attack mediated by organoaluminum complexes this provides an explanation of the need for 3 equiv. MesAl for the fast reaction (Sch. 35). 

The scope of biochemical GC would be quite limited without sample derivatization. Yet, a simple chemical conversion of the compounds of interest into suitable derivatives is frequently all that is required for successful chromatography. Benzoic acid, typical of many naturally occurring substances which, because of their polarity, are not well suited for gas-chromatographic analysis, is readily converted by treatment with methanol in the presence of an acidic catalyst (such as boron trifluoride) into the thermally stable methyl benzoate, which is more volatile than the parent acid and becomes easier to chromatograph. As another example, GC properties are favorably affected when the typical alcohol cholesterol is converted to the silyl ether by simple treatment with chlorotrimethylsilane in pyridine. 

For dynamic studies, the IR cell reactor was used. After zirconia activation in hydrogen at 400°C, the temperature was reduced to 200°C and methyl benzoate (2.7 Torr) was fed with the hydrogen flow (15 ml. min-i). At this temperature, the catalyst activity was low (conversion = ca 3 %). The first species formed on the surface were methoxy groups, partly formed at the expense of free zirconia OH groups at 3763 (type I) and 3654 cm- (type II). Then benzoate species appeared... 

Synthesis of Aromatic Nitriles from Esters. A one-flask method has been developed for the conversion of aromatic esters to the corresponding nitriles by use of NaHMDS in a sealed tube at 185 °C in a mixture of THF and 1,3-dimethyl-2-imidazolidinone (DMEU) (eq 20). The transformation proceeded with good to excellent yields. The synthetic strategy is only apphcable to aromatic esters that bear an electron-donating substituent such as hydroxy or methoxy. In the latter case, con tetitive 0-demethyla-tion is observed, thus leading to a mixture of nitrile products. The reaction has been also applied to indole-3-carboxylate. However, simple unsubstituted methyl benzoate failed to give the desired product. 

Benzaldehyde in methanol containing a catalytic amount of HCl irradiated 5 hrs. at 5° with a 100 w. immersion-type high-pressure Hg-lamp under a stream of oxygen methyl benzoate. Y 90% conversion 25%. F. e. s. H. Sakuragi and K. Tokumaru, Chem. Lett. 1974y 475. 

Discuss the differences observed in the IR and NMR spectra of methyl benzoate and triphenylmethanol that are consistent with the conversion of an ester into a tertiary alcohol in this experiment. 

Nitration of hydroxypropiophenone (7-1) followed by conversion of the phenol to its methyl ether by means of methyl iodide provides the intermediate (7-2) the nitro group is then reduced to the corresponding amine (7-3) by catalytic reduction. The newly introduced amine is then replaced by a nitrile group by successive conversion to the diazonium salt by means of nitrous acid followed by treatment with cuprous cyanide (7-4). Reaction with aluminum chloride removes the methyl ether to afford the ortho acylphenol (7-5). This is converted to the chromone (7-6) as above by reaction with benzoyl chloride and sodium benzoate. The nitrile is next hydrolyzed to the carboxylic acid (7-7) by means of sulfuric acid. The acid is then converted to its acid chloride by means of thionyl chloride and that treated with 2-(A -piperidyl)ethanol (7-8). There is thus obtained flavoxate (7-9) [8], a muscle relaxant whose name reflects its flavone nucleus. 

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