Methyl groups aromatization with

Recent computer modeling clearly shows that for molecules such as 4,6-dimethyldibenzothiophene (4,6-DMDBT), the methyl groups interfere with catalyst-molecule interactions as the sulfur atom adsorbs primarily through a one-point attachment and the dibenzothiophene ring system is nearly perpendicular to the catalyst surface. Hydrogenation of one ring of the 4,6-DMDBT causes the rigid planar aromatic structure to pucker and allow much better interaction between the sulfur atom and the catalyst surface (77). 

Precursors such as reticuline 10 were synthesized labelled with 14C (O and N methyl groups) and with 3H in the aromatic nuclei. Labelling could also be done in the two 2-carbon bridges. We also synthesized from thebaine the key alkaloid 11 for the first time. Unlike the situation with Pummerer s ketone 11 did not close to 12 spontaneously. Later on, alkaloid 11 was isolated from a Brazilian plant. From correspondence with Prof. R. A. Barnes, we realized that the two were probably identical, which was confirmed by an exchange of specimens. So, we used thereafter the name salutaridine, given by our Brazilian colleagues. 

Hyperconjugation of a methyl group combined with an aromatic nitrogen cation (A+) can be written. 

Occasionally, however, a ring methyl group arises from the carboxyl carbon after total reduction, as in the formation of bamol (XXVIII) (Mosbach and Ljungcrantz, 1965) or javanicin (XXIX) (Gatenbeck and Bentley, 1%5). Only the methyl groups marked with an asterisk in these structures are derived from methionine (see also Scheme 2). It should also be remembered that alkylation may occur at nucleophilic positions of aromatic precursors in susceptible products of shikimic acid origin, as in the synthesis, for example, of plastoquinone and ubiquinone (Threlfall et al., 1968). 

The range of compounds which combine with thiourea is still more varied. As regards their formation, the rule is that clathrates are most easily formed from aliphatic compounds with two methyl groups or with substituents of approximately the same size (halogens) in the chain. A larger side chain (ethyl, isopropyl) prevents the formation of clathrates with thiourea. Thiourea also forms adducts with cycloparaffins simple aromatic compounds (benzene, nahphthalene, anthracene) do not form clathrates with thiourea. 

Finally the chemical aromatization of Ring A which occurs in nature in the biosynthesis of estrogens must be mentioned. It can be done by thermal cleavage of the C-19 methyl group in 1,4-dien-3-ones (H.H. Inhoffen, 1940 C. Djerassi, 1950) and was later achieved at lower temperatures with lithium — biphenyl in THF (H.L. Dryden, Jr., 1964). 

Aromatic nitriles are converted into a methyl group with ammonium for-mate[109]. Aldehydes and ketones are reduced to alcohols[l 10],... 

Donor substituents on the vinyl group further enhance reactivity towards electrophilic dienophiles. Equations 8.6 and 8.7 illustrate the use of such functionalized vinylpyrroles in indole synthesis[2,3]. In both of these examples, the use of acetyleneic dienophiles leads to fully aromatic products. Evidently this must occur as the result of oxidation by atmospheric oxygen. With vinylpyrrole 8.6A, adducts were also isolated from dienophiles such as methyl acrylate, dimethyl maleate, dimethyl fumarate, acrolein, acrylonitrile, maleic anhydride, W-methylmaleimide and naphthoquinone. These tetrahydroindole adducts could be aromatized with DDQ, although the overall yields were modest[3]. 

As early as 1889 Walker (320), using samples of thiazole, 2,4-dimethylthiazoie, pyridine, and 2,6-dimethylpyridine obtained from Hantzsch s laboratory, measured the electrical conductivity of their chlorhydrates and compared them with those of salts of other weak bases, especially quinoline and 2-methylquinoline. He observed the following order of decreasing proton affinity (basicity) quinaldine>2,6-dimethyl-pyridine>quinoline>pyridine>2,4-dimethylthiazole> thiazole, and concluded that the replacement of a nuclear H-atom by a methyl group enhanced the basicity of the aza-aromatic substrates. 

Poly(phenylene oxide)s undergo many substitution reactions (25). Reactions involving the aromatic rings and the methyl groups of DMPPO include bromination (26), displacement of the resultant bromine with phosphoms or amines (27), lithiation (28), and maleic anhydride grafting (29). Additional reactions at the open 3-position on the ring include nitration, alkylation (30), and amidation with isocyanates (31). 

A tertiary carbonium ion is more stable than a secondary carbonium ion, which is in turn more stable than a primary carbonium ion. Therefore, the alkylation of ben2ene with isobutylene is much easier than is alkylation with ethylene. The reactivity of substituted aromatics for electrophilic substitution is affected by the inductive and resonance effects of a substituent. An electron-donating group, such as the hydroxyl and methyl groups, activates the alkylation and an electron-withdrawing group, such as chloride, deactivates it. 

The ansa-chain of the ansamycins streptovaricins (4), rifamycins (263), geldanamycin (4), and herbimycin (32) has been shown to be polyketide in origin, being made up of propionate and acetate units with the 0-methyl groups coming from methionine. The remaining aromatic C N portion of the ansamacroHdes is derived from 3-amino-5-hydroxybenzoic acid (264—266) which is formed via shikimate precursors. Based on the precursors of the rifamycins and streptovaricins isolated from mutant bacteria strains, a detailed scheme for the biosynthesis of most of the ansamacroHdes has been proposed (95,263). 

Aldehydes, Ketones, ndAcids. As with many aromatic compouads, the oxidatioa of methyl groups is an attractive synthetic route to both aldehydes and carboxyUc acids ia the quiaoliaes. The hydrolysis of dibromomethyl groups has also beea used for aldehydes and the hydrolysis of nitriles for carboxyhc acids. Detailed reviews of the synthesis of these compounds have appeared (4). 

Aromatic aldehydes (100), eg, cinnamaldehyde, and ketones (101) react ia a similar manner (eq. 4). Ketones containing reactive methyl or methylene groups give with succiaates, ia the presence of sodium hydride, both the Stobbe condensation and the formation of diketones by a Claisen mechanism (102) (eq. 5). 

The halogenation reaction conditions can be chosen to direct attack to the methyl group (high temperature or light to form free-radicals) or the aromatic ring (dark, cold conditions with FeX present to form electrophilic conditions). 

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