Murahashi, Shunsuke published the artcile< New derivatives of o-xylene>, Category: esters-buliding-blocks, the main research area is .
The present work concerns itself with the synthesis of o-hydroxymethylphenylacetic acid (II), HOCH2C6H4CH2CO2H, and its derivatives which hitherto have not been prepared The simplest method for preparation of II from o-C6H4(CH2Br)2 (I) seemed to be a displacement of a Br atom by means of a nitrile group and then hydrolysis of the resulting compound This method was found to be unsatisfactory. The reaction mixture consisted of a colorless oil, N-free and containing 0.8% Br, which reacted with the Grignard reagent with the evolution of CH4. 20.8 g. I was dissolved in a mixture of 60 cc. EtOH and 20 cc. H2O and brought to boiling. KCN (5.2 g. in 20 cc. H2O) was added in small portions with shaking. After 2-2.5 hrs. heating the mixture was poured into 1 l. H2O and extracted with Et2O. The ether solution after drying and removal of the solvent was fractionated; 9 g. colorless liquid, b17 122-135°. On refractionation, a fraction was obtained, b17 122-4°, which consisted largely of o-ethoxymethylbenzyl alc. (III) and a small quantity of I. This fraction was dissolved in Et2O and decomposed with freshly cut pieces of Na and allowed to stand several days with occasional removal of the precipitate formed at the surface of the Na. The precipitate was dissolved in H2O, washed with Et2O, acidified and extracted with Et2O. On distilling, a colorless liquid, b1 130-40°, was obtained. Later it solidified and m. 85-6°. Analysis showed it to be o-ethoxymethylbensoic acid (IV), C10H12O3. This is accounted for through an oxidation of a -CH2OH group in III to a carboxyl group. o-Dimethoxymethylbenzene (V), C6H4(CH2OMe)2, prepared from 39.6 g. I and MeONa (from 11 g. Na), in 20 g. yield, b25 117-19°, b16 109-11°. o-Methoxymethylbenzyl chloride (VI), was prepared by dissolving 20 g. V in 16 cc. anhydrous CCl4 and treating with a solution of 6.6 g. (0.7 mol.) AcCl. Reaction started with addition of a trace of fused ZnCl2. After cooling to room temperature, diluting with Et2O and washing with H2O, the ether layer was dried and fractionated. A colorless oil strongly irritating to the eyes, b22 116-21°, and consisting of a mixture containing more than 0.5 its weight of V was obtained. This oil was treated with a KCN solution in quantity corresponding with the AcCl consumed (5.8 g. KCN + 30 cc. EtOH + 10 cc. H2O). After 3 hrs. heating the reaction mixture was cooled, poured into H2O and fractionated, after extraction with Et2O. The product, o-methoxymethylphenacetonitrile (VII), was a colorless oil b17 151-3°. The regenerated V can be reemployed after purification with alc. KOH. From 212 g. V, 198 g. of a mixture of V and VI was obtained and this yielded 84.9 g. VII. The lactone (VIII) of o-hydroxymethylphenylacetic acid, prepared by hydrolysis of VII under varying conditions (constant boiling HBr, 1:1 and 1:2 H2SO4), m. 82.5-3.5°. A by-product of o-bromomethylphenacetonitrile (IX), m. 92-2.5°, also forms when HBr is the hydrolytic reagent. When VII is hydrolyzed with concentrated HCl o-chloromethylphenylacetic acid (X), m. 118-18.5°, was obtained. o-Methoxymethylphenylacetic acid (XI) was prepared by refluxing 20 g. VII with 60 g. KOH + 300 cc. alc. on a water bath for 11 hrs. and then working up the product in the usual manner. Yield, 76% of a colorless oil b2 136-49°. Two recrystallizations from petr. ether gave prisms m. 52-4°. The Cu, Ag and Pb salts were prepared The 1st 2 mentioned salts are difficultly soluble in H2O. o-Methoxymethylphenylacetamide (XII) was prepared by dissolving 15 g. VII in the calculated weight of absolute EtOH and saturating the solution with dry HCl gas. Recrystallization of the solid which appeared on long standing from CHCl3-CCl4 yielded crystals m. 117-18°. Hydrolysis of XII with alc. KOH yields XI. The corresponding Et ester of X was obtained by dissolving 4.25 g. VIII in 30 cc. absolute EtOH and passing dry HCl gas into the mixture for 30 min. with warming. Following removal of the solvent, the residue was diluted with H2O and extracted with Et2O, the latter washed with dilute NaOH, dried with CaCl2 and distilled 4.5 g. colorless oil, b23 163-4°, was obtained. Saponification of the latter compound, Et o-chloromethylphenylacetate, yielded VIII. A byproduct from the saponification which was not identified m. 124-4.5°. 15 g. XI, when warmed cautiously with 18 g. SOCl2, yielded 10 g. yellow oil, b4 126-36°, and a large fraction of black residue. The oil analyzed 16.8% Cl and became dark at its surface on standing. 4.48 g. of the latter oil on hydrolysis with 40 cc. 2 N KOH yielded 1.25 g. precipitate The filtrate on acidification yielded 1.4 g. VIII. The previously mentioned precipitate was dissolved in Et2O, the insoluble matter filtered off and the filtrate concentrated Several recrystallizations of the resulting crystals from petroleum ether and MeOH yielded a product soluble in Me2CO, CHCl3, C6H6, Et2O, which m. 126-6.3° and whose analysis and mol. weight corresponded closely with C20H20O4. From the Et2O mother liquor another batch of crystals was isolated which upon recrystallization first from MeOH and then EtOH m. 198-9°. Analysis and mol.-weight determinations indicated the latter was C28H36O6. The interaction of XI with POCl3 is also unusual. Although POCl3 did not react with the carboxyl group it was impossible to detect unchanged acid in the C6H6-reaction mixture Besides a small quantity of VIII, 2 neutral liquids (a) and (b) were isolated. The former, b1 200-210° and does not react with alkali. The latter b1 140-150°, and reacts with alkali, whereby a monobasic acid m. 93.5-4.5° is formed, and which analyzes for C15H14O2. Although this acid is not described in the literature it must be o-benzylphenylacetic acid and thus the reaction of XI with POCl3 in C6H6 proceeds in an unusually complicated manner; removal of a Me group, condensation with the solvent, esterification, and an unknown step leading to the formation of (a) occur one after the other.
Scientific Papers of the Institute of Physical and Chemical Research (Japan) published new progress about 112-63-0. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Category: esters-buliding-blocks.
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