Methanolysis acid chlorides

Friedel-Crafts acylations are unknown for the azoles, clearly because of interaction between the basic nitrogen and the Lewis-acid catalyst. It is, however, possible to 2-aroylate 1-alkyl-imidazoles " or indeed imidazole itself by reaction with the acid chloride in the presence of triethylamine, the substitution proceeding via an iV-acyl-imidazolium ylide. Trifluoroacetylation of iV-substituted imidazoles, and some oxazoles and thiazoles, also produces 2-substituted products in good yields. In the reverse sense, 2-acyl-substituents can be cleaved by methanolysis, the mechanism again involving an imidazolium ylide. ... 

Kupchan et al. achieved the first total synthesis of aristolochic acid involving photocyclization of substituted 2-iodostilbenes [410], Piperonal (689) provided a suitable skeleton to build ring A of aristolochic acid. It was reduced to the piperonoyl alcohol (690) with lithium aluminium hydride. Bromination of 690 afforded 6-bromopiperonoyl bromide (691). It was then hydrogenated to the corresponding 2-bromo-4,5-methylenedioxytoluene by w-butyllithium carbonation method. The toluic acid (693) was converted to acid chloride by oxalyl chloride, and bromination of acid chloride and by radiation with a 200-W tungsten lamp followed by methanolysis afforded the ester 694, which on treatment with silver nitrate produced methyl ester (695). 

A related route reacted enamino-nitrile I.I7S with phosgene (another carboxyl surrogate) to give 7.27d. 5 Methanolysis of the acid chloride gave methyl 3-amino-... 

In contrast to the hydrolysis technology, the methanolysis process allows for the one-step synthesis of organosdoxane oligomers and methyl chloride without formation of hydrochloric acid (64,65). The continuous methanolysis can also yield quantitatively linear sdanol-stopped oligomers by recycle of the cycHc fraction into the hydrolysis loop. 

G.l.c. studies of tributylphosphine, dialkyl phosphites, and dialkyl alkylphosphonates are reported. Tributyl phosphate in nitric acid can be estimated by g.l.c. if a glass column is used. Tetraethyl pyrophosphate has been directly determined on a nanogram scale by g.l.c., whereas it was found most convenient to first convert the tetra-aryl pyrophosphates by methanolysis to diarylmethyl phosphates. Phosphorochloridates were converted by t-butyl alcohol into t-butyl chloride before analysis. G.l.c. studies of pesticides have been reported and the isomeric thiophosphates (138a) and (138b) have quite different retention times. ... 

The phosphonyl adduct 300 reacted with a dilute solution of anhydrous hydrogen chloride in ethanol or with sodium ethoxide to afford an essentially quantitative yield of the P-N cleaved product 304 with inversion of configuration. Addition of sodium ethoxide to a solution of 304 in methanol resulted in the formation of enantiomerically pure (+)-(.V)-ethyl methyl phenylphosphonate (305). It also reacted quantitatively with methylmagnesium iodide at room temperature to give the product of P-S bond cleavage 306, which upon acid catalyzed methanolysis afforded enantiomerically pure (+)-(R)- methyl methylphenylphosphinate (307) (Scheme 72) [108],... 

The same authors <2000J(P1)3584> studied the reactivity of 2 toward benzenediazonium (chloride or tetrafluoro-borate) salts. No diazo coupling took place under neutral or slightly acidic conditions. However, under basic conditions (NaOH in H20/MeOH), a mixture of 62 and 63 was obtained. This result clearly indicates that the diazo coupling takes place through the anion of 62 which arises from the base-catalyzed methanolysis of amide 2 in which the pyrrole ring is obviously not nucleophilic enough. 

Glycosidic linkages may also be cleaved in other solvents, such as methanol. In this case, water is rigorously excluded, so that the elements of a molecule of methanol are added across the glycosidic linkage to afford the methyl glycosides. Methanolysis is usually catalyzed by the addition of dry hydrogen chloride to the methanol. Other solvents, such as acetic anhydride-acetic acid (acetolysis) and formic acid (formolysis), are occasionally used for special purposes. 

Methanolysis of standard uronic acids has been studied by Inoue and Miyawaki in regard to the depolymerization of chondroitin sulfate and dermatan sulfate. These workers found the glucosiduronic linkage to ga-lactosamine to be rather resistant to methanolysis, but that it is more efficiently cleaved after deamination of the amino galactoside, with its conversion into 2,5-anhydrotalose. For iduronic, glucuronic, and man-nuronic acids released from a polymer, it was found that the peaks monitored for these acids, relative to an internal standard, increase during the first 8 h of methanolysis (M hydrogen chloride, 100°) and remain constant for up to 20 h of methanolysis. This indicated that 8 h is required for complete methanolysis, and that the monosaccharides liberated are stable to the conditions of methanolysis. 

Chaplin used methanolysis for the analysis of carbohydrates in glycoproteins. His method was a variation of the foregoing procedures, with an improvement of using tert-hvAyX alcohol to remove hydrogen chloride by coevaporation, instead of prolonged trituration with silver carbonate. His method is useful for samples containing uronic acids and lipids. Mononen studied methanolysis, followed by deamination and reduction with borohydride, for determination of the monosaccharide constituents of glycoconjugates. This method was applied to a lipid-free, protein fraction of rat brain. 

The medicinal chemistry of this period relied on simple modifications of the complex alkaloids. Deacetylation of 1 produced 4-deacetylvinblastine (98), a perfect substrate for these first experiments. Treatment if 1 with hydrogen chloride in anhydrous methanol gives 98 directly (91). Cleavage of the 4-acetyl function can also be effected by methanolysis, but during this period the acid-catalyzed methanolysis method was regarded as the preferred method. 

The above hydrochloride is treated with thionyl chloride in liquid sulfur dioxide, to produce an amorphous chloride hydro chloride, which is converted to the nitrile with sodium cyanide in liquid hydrogen cyanide, Methanolysis then gives the ester of the nitrile. Alkaline hydrolysis of this last compound, followed by catalytic dehydrogenation in water using a deactivated Raney Nickle catalyst (see JOC, 13, 455 1948) gives dl-lysergic acid. 

The problems inherent in the hydrolysis of methylated polysaccharides are similar to those outlined, but, in addition, the possibility of occurrence of demethylation must be considered. This matter has been studied by Croon and coworkers,102 who found that hydrogen chloride, either in water or methanol, causes a significant amount of demethylation. Formolysis in 98% formic acid caused considerable degradation, whereas 90% formic acid or sulfuric acid gave acceptable results. The hydrolysis of a methylated dextran with 90% formic acid has been described in detail.103 The methanolysis of a methylated... 

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