Methyl benzoate reduction

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... 

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],... 

Overlap from resin signals, mentioned previously, can be overcome in several ways, and is particularly important when following reactions involving aromatic groups attached to polystyrene based resins. Spin echo MAS NMR was applied to follow the progress of a reduction of a resin-bound methyl benzoate to the alcohol.45 One-dimensional H as well as COSY and TOCSY spectra were used to elucidate the reaction products, although transformations were readily apparent in the ID spectra alone. 

The following sequence is also appropriate once methanol and benzyl alcohol are obtained by reduction of methyl benzoate ... 

Esters, like carboxylic acids, are normally reduced with lithium aluminum hydride. In these reactions, two alcohols are formed. An example is the reduction of methyl benzoate to benzyl alcohol and methanol. 

The photolysis of hexachloroacetone or tribromoacetaldehyde in methanol does not yield any alcoholysis product253. The major reaction is reduction. On the other hand, a,a,a-tribromoacetophenone yields the alcoholysis product methyl benzoylformate in good yield (equation 56)254. The initial photomethanolysis product is a,a-dibromo-a-methoxy-acetophenone, which in a dark reaction is converted into the benzoylformate. The methyl benzoate is formed by nucleophilic attack on the carbonyl carbon. 

Bis[4-methoxyphenyl] tellurium, obtained from 4-methoxybenzene and tellurium tetrachloride and reduction of the resultant bis[4-methoxyphenyl] tellurium dichloride, was converted to methyl 4-methoxybenzoate in 99% yield1. Methyl benzoate was similarly obtained from diphenyl tellurium in yields higher than 90%. These reactions can be carried out with catalytic amounts of palladium(II) chloride when copper(II) chloride is used as an oxidant1. 

Methylation of the lactam nitrogen and condensation with methyl benzoate in the presence of lithium diethylamide in THF afforded a ketone, which, on sodium borohydride reduction, yielded racemic isocynometrine (99) as the major component of a mixture of two epimeric phenyl carbinols (Scheme 8) (155). Racemic anantine (94) and cynometrine (95) have been synthesized analogously, starting from 4-formyl- 1-methylimidazole (155). 

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. 

Voltammetric data for ester reductions are available for several aromatic esters [51-54], and in particular cyclic voltammetry shows clearly that in the absence of proton donors reversible formation of anion radical occurs [51]. In dimethylfonnamide (DMF) solution the peak potential for reduction of methyl benzoate is —2.29 V (versus SCE) for comparison dimethyl terephthalate reduces at —1.68 V and phthalic anhydride at —1.25 V [4]. Half-wave potentials for reduction of aromatic carboxylate esters in an unbuffered solution of pH 7.2 are linearly correlated with cr values [51] electron-withdrawing substituents in the ring or alkoxy group shift Ei/o toward less negative potentials. Generally, esters seem to be more easily reducible than the parent carboxylic acids. Anion radicals of methyl, ethyl, and isopropyl benzoate have been detected by electron paramagnetic resonance (epr) spectroscopy upon cathodic reduction of these esters in acetonitrile-tetrapro-pylammonium perchlorate [52]. The anion radicals of several anhydrides, including phthalic anhydride, have similarly been studied [55]. 

Other reductions. Miller et report reduction of benzoic acid and of methyl benzoate to benzyl alcohol and of n-butyl caproate to n-butanol and n-hexanoL Russian investigators" report reduction of aliphatic and aromatic esters to aldehydes, of ortho esters to acetals, of acetals to ethers, and of benzyl ethyl ether to toluene. 

Reduction. Ketones which have no a-hydrogen are reduced by sodium hydride. Thus benzophenone when heated with a slight excess of reagent in xylene at 145° for six hours was reduced to benzhydrol in 83% yield. Under the same conditions methyl benzoate is not reduced. 

Usually the C-0 single bond in esters is cleaved at the acyl-0 bond, whereas examples of cleavage at the other point in esters have been reported. An electron-rich iron(O) complex produced on reductive elimination of naphthalene from a hydrido(naphthyl)iron complex undergoes oxidative addition reaction with methyl benzoate to give a methyliron benzoate complex (Eq. 22) [63]. 

Moreover, a-cyano-a-epoxy esters are easily reduced to a-cyano-a-epoxy alcohols by NaBH4 in aqueous THF [MR4]. Ethanedithiol can also be an additive for the reduction of esters by NaBH4, except r-butyl esters. Nitrile groups remain unperturbed under these conditions [GEl]. Methyl benzoate is reduced to benzylalcohol by NaBH4-ZrCl4 in THF [ISl],... 

The reduction of benzaldehyde was also studied at 350°C. The activity of the various metal oxides, particularly that of CeOa and TiOa. was lower than that found for methyl benzoate. Therefore, benzaldehyde is less easily reduced than methyl benzoate explaining the high seiectivity of these metal oxides for the hydrogenation of the latter (Table 1). 

Our preliminary studies show that the catalyst system can tolerate at least some functionalities on the arene thus, while substrates containing unprotected -OH or COoH groups are hydrogenated only to a small degree or not at all, aryl-ethers (anisole), -esters (methyl benzoate), -ketones (acetophenone, benzophenone), and N,]V-dimethylaniline are all hydrogenated. In general, no products corresponding to states of intermediate reduction (cyclohexenes or cyclohexadienes) are detected. 

Cyclohexenone is reduced to cyclohexanone, whereas excess reagent leads to the formation of cyclohexanol. Cyclohexanone is preferentially reduced in the presence of benzyl chloride. Under the reaction conditions, methyl benzoate and benzylcyanide do not undergo reduction. Consequently, the lithium di-n-butyl ate complex of 9-BBN permits [33] the chemoselective reduction of aldehydes in the presence of ketones, esters, and nitriles. 

Yields of primary and secondary alcohols are generally excellent, but esters such as methyl benzoate were not reduced. Results of typical examples are listed in Table I. Both 2 and 3 predominantly afforded 2-cyclohexenol as the 1,2 reduction product from 2-cyclohexenone. Chemoselectivity in the reduction was also demonstrated by the competitive reduction of a mixture of pentanal and cyclohexanone. The ratios of primary and secondary alcohols were 75/25 for 2 at 0 °C and 79/21 for 3 at room temperature. These values are fairly larger than the corresponding one (63/37) from a mixture of butanal and methyl ethyl ketone reduced by LiAlH at 25 but smaller than those from a mixture of hexanal and cyclohexanone with LiAlH(0-f-Bu)3 at 0 °C (87/13) and LiAlH(OCEt3)3 at 0 °C (94/6).10... 

In order to gain more informations on the nature of the complex borohydride Na(PEGBH2), the reduction of esters was examined using NaBH in PEG 200, 300 and monomethoxy PEG. From these results it appears that methyl benzoate is completely reduced in PEG 200, whereas the same reduction in PEG 300 is complicated by a partial hydrolysis of the ester to benzoic acid. Finally, if one of the two hydroxy groups of PEG is blocked as ether no reduction at all takes place (Scheme 7). 

With C, things have become more transparent, as the amino group may derive from reduction of the nitro group in D, the product of nitration of methyl benzoate, E, our ultimate starting material. 

NOTE. Many esters reduce Fehling s solution on warming. This reduction occurs rapidly with the alkyl esters of many aliphatic acids, but scarcely at all with similar esters of aromatic acids (f.g., ethyl oxalate reduces, but ethyl benzoate does not). Note also that this is a property of the ester itself thus both methyl and ethyl oxalate reduce Fehling s solution very rapidly, whereas neither oxalic acid, nor sodium oxalate, nor a mixture of the alcohol and oxalic acid (or sodium oxalate), reduces the solution. 

Base-catalyzed condensation between phenylacetic acid and phthalic acid produces enol lactone 78, which is reduced to benzoate 79 with HI and phosphorous. Friedel-Crafts cyclization by polyphosphoric acid followed by reduction produces alcohol 80. This alcohol forms ethers exceedingly easily, probably via the carbonium ion. Treatment with N-methyl-4— piperidinol in the presence 6f acid leads to the antidepressant hepzidine (81). 

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