Ortho-Substituted Chlorobenzenes Related to Metameconine

Abstract

Chlor~~iatcd derivatives of metameconine wcre formed for ihc first time. Partial demethylation of the derivatives with sulphuric acid occi~rred in highly selective fashion a t the 111ethoxyl ortho to the llalogen, without regard to the relative position of the carbonyl group which is Icno\vi~ to be highly directive for demethylatiolis in the absence of halogen. The phenolic products of the clemethylations are needed for the synthesis of sterically hindered cliphenyl ethers. They showed a type of intermolecular hydrogen bonding in the crystal which mas marlcedly subject to steric interference by thc halogen atoms.Our work with the cl~lorinated derivatives of metameconine (X) was first unc1c1-taken nlany years ago as a checlc upon the results we had obtained in the correspo~lding bromine series (1, 2, 3 ) ; these results had differed sharply fro111 those reported by others (4). The need for a check was emphasized when our inore recent worlc (5) led to solnewhat surprising conclusio~~s a s to the direction of brornination, nitration, and selective demethylation in the metameconi~les. This paper reports the independent characterization of the chlorine series of compounds, sllows that the chlorine series is an alnlost exact parallel to the bromine series, and therefore thoroughly verifies our previous results.TWO more reasons for proceeding with the chlorine series appeared later in our work.( a ) A subject of continuing interest to us is the study of steric hindrance in dipllenyl ethers (3, 6); obviously the ortho-chloro-and ortho-bro~no-phenols obtained in this work will alloxv the preparation of corresponding cliphenyl ethers with bloclcing groups of different sizes. (b) We hope to study the effect of crowding upon the quadrupole resonance frequency of the halogens; measurement of these frequencies is, of course, easier for chlorine compounds than for bromine or iodine compounds.The nlain novelty of the present worlc lies in the description of a n interesting steric. hindrance of hydrogen bonding in the solid phase. Synthesis a d S t r~l c t~l r eThe most easily available of the chlorine derivatives was 7-chloron~ctameconi~~c~ (XI I ) , made from metameconine (X) by nitration, reduction to the amine (XI) (1, 2, 4), diazotization of the amine, and the Sandrneyer reaction. No doubt the structure was obvious, since 7-bromomcta~~~econinc (1, 2, 4) and 7-iodometameco~li~le (1, 3), formed in corresponding ways, have had their structures tl~orouglily verified. Nevertheless the present I\-orl; offered a quite independent proof that the new substance was indeed 7-chlorornetameconine, its indirect formation from 2-chloroveratric acicl (XIV), as show11 in the chart, leaving no room for doubt as to its structure.The iso~lleric 4-chlorometameco~~i~~e (VII) was formed by the action of for~nalclel~ydc ilpon 5-chloroveratric acid (VI) in acid solution. The structure of the resulting phthaliclc

Metameconine as a Model Compound in the Study of Aromatic Reactions

“…Hydroxyl groups d o not appreciably bond with phthalide carbonyl groups ortho t o then1 (7,12), but the fact t h a t VI has a much lower melting point than its geometrically Can. J. Chem.…”

“…The structure of the product was proved by its preferential reduction (4, 7) t o the known 7-cl~loron~etameconine (VIII) (7). One more surprise remained.…”

“…Previous work showed that metameconine is preferentially demethylated a t position 6 (4), and the same argument may be extended to other demethylations. However, our further experi~nental work on the dernethylation of halogenated metailleconines (4,7) &owed that the second step is the deter~nining step in still other reactions of this Bind, and it is liliely that further progress can be made only by more quantitative methods.…”

Degradation of Methoxylated Benzoic Acids by a Nocardia from a Lignin-Rich Environment: Significance to Lignin Degradation and Effect of Chloro Substituents

“…Spectrophotometric observation of protocatechuate oxidation by a cell-free extract. Dotted line, protocatechuate spectrum; dashed line, 1 min after addition of cell-free extract; solid line,30 min after addition of cell-free extract. Metabolism of veratric acid and p-methoxybenzoic acid by Nocardia corallira A81.…”