Acetyl bromide hydrolysis

The key to clinical agents in this series, the secondary amine, 65, is obtained by a sequence analogous to that used to obtain desmethymorphine. Thus, the phenol (63) is first acetyl-ated (64), and then demethylated by treatment with cyanogen bromide hydrolysis gives the desired aminophenol (65). Alkylation... 

The reactions of 0-naphthol and 4-methoxyphenol with acetyl, propionyl, butyryl, 0-chloropropionyl and chloracetyl chlorides in acetonitrile produce some striking kinetic results109. The behaviour of acetyl, propionyl and n-butyryl chlorides fit reasonably well into the pattern for acetyl chloride in nitromethane and acetyl bromide in acetonitrile. However, with chloracetyl chloride the mechanism is essentially a synchronous displacement of covalently bound chlorine by the phenol and this process is powerfully catalysed by added salt with bond breaking being kinetically dominant. When no added salt is present the rate of hydrolysis of chloracetyl chloride is ca. 8000 times slower than that of acetyl chloride. Although, normally, in second-order acylation reactions, substituents with the greatest electron demand have been found to have the fastest rates, the reverse is true in this system. Satchell proposes that a route such as... 

The four related compounds oxalomycin (157), neooxalomycin (158), cur-romycin A (159), and curromycin B (160) were reported in 1985 157 and 158 were isolated from a yet to be identified Streptomyces species (79, 80) and 159 and 160 from an ethidium bromide-treated strain of S. hygroscopicus (81, 82). The absolute configuration of oxalomycin (157) and neooxalomycin (158) has been determined by application of a combination of X-ray crystallography and chemical correlation to degradation products, the important derivatives being the p-bromobenzoate 161, obtained from 157 by ozonolysis-reduction, acetylation, partial hydrolysis, and reacylation with p-bromobenzoyl chloride, and the erythro acetate 162 which was obtained along with the threo compound 163 after acetylation of the ozonolysis products of 157 (79, 80). No stereochemical infor-... 

Each structural assignment of signals 1-7 in the spectrum of Figure 4 is based on the addition of the authentic compound to the crude ozonolysis mixture, and—aside from peak 1—is also based on additional analytical evidence 2,2,3,3-tetrabromobutane (peak 2), 3,3-dibromobu-tanone (peak 4), and acetic acid were actually isolated while acetyl bromide (peak 3) as well as acetic anhydride (peak 5) were further identified by their sensitivity to solvolysis reactions, particularly hydrolysis and alcoholysis to form the corresponding esters. Diacetylperoxide (peak 6) was identified by the disappearance of peak 6 from the NMR spectrum as well as the disappearance of the typical infrared bands at 1810 and 1835 cm"1 when the reaction mixture was treated with sodium iodide. 

Spontaneous hydrolysis of acetyl bromide, 25, leads to the formation of acetic acid, 28, acetic anhydride, 29, and hydrogen bromide. Since there is always excess ozone present, hydrogen bromide is rapidly reoxidized to form bromine and to reform the water. Therefore, the sequence depicted above can be summarily represented by the following reaction ... 

Nitro-6-chloropyridazine 1-oxide reacts with nucleophiles with displacement of the 6-chlorine atom (even with acetyl bromide), except with sodium methoxide. Merer, the 3-nitro group is diplaced. Nucleophilic substitution with amines was investigated for various monoalkoxydihalo-or dialkoxyhalopyridazines. Normally, the chlorine atom is replaced, but in 3-chloro-4,6-dialkoxy- or 4-alkoxy-3,6-dichloropyridazines the alkoxy group may be replaced preferentially or concurrently. The 6-chlorine atom of methyl (3,6-dichloropyridazin-4-yl)-acetate was displaced by hydrazine or on hydrolysis. ... 

Zeehmeister found that commercial acetyl bromide (which contains hydrogen bromide and acetic acid) reacts very rapidly with cellulose, but that the reaction with pure acetyl bromide is very slow. The reactivity of the acetyl bromide increases with the addition of increasing proportions of water, because of resultant hydrolysis. 

Hydrogenation was carried out at O to minimize decarboxylation of the saturated 3-keto acid product 18. Mannich reaction proceeded with in situ decarboxylation to afford a-methylene ketone 19, which on Michael reaction with ketal 3 keto ester 20 -" yielded adduct 21. Saponification, B ring closure, and decarboxylation then led to ketalenone 23 in high yield, which was converted into ( + )-19-nortestosterone 24 and thence to ( + )-19-norandrostenedione 25 in 50% yield from 18 or 27% overall yield from 12. However, ketal hydrolysis, A ring closure, oxidation at C-17, and isomerization by the Roussel procedure (acetyl bromide-acetic anhydride in methylene chloride at 20°) should yield (-f )-estrone 26 efficiently. 

When 35 was heated in acetic acid containing hydrogen bromide, the tribromide 46 was obtained as a single product in 74% yield. Debromina-tion of 46 with zinc dust in acetic acid furnished the cyclohexene derivative 47, which was converted into compound 48 by osmium tetraoxide hydroxyl-ation and acetylation. The substitution reaction of 48 with acetate ions provided carba-a-DL-glucopyranose pentaacetate (49), which gave the carba-sugar 50 on hydrolysis. ... 

In the reaction with PNPA, myristoylhistidine [29] in a cationic micelle rapidly forms acetylimidazole as a fairly stable intermediate which is readily observable at 245 nm. On the other hand, a mixed micelle of [29] and N,N-dimethyl-N-2-hydroxyethylstearylammonium bromide [30] leads to the formation and decay of the intermediate, indicating that the acetyl group is transferred from imidazole to hydroxyl groups (Tagaki et al., 1977 Tagaki et al., 1979). This can be a model of cr-chymotrypsin which catalyses hydrolysis of PNPA (non-specific substrate) by initial acylation of the histidyl imidazole followed by acyl transfer to the seryl hydroxyl group (Kirsh and Hubbard, 1972), as indicated schematically in (12). 

The selective hthiation of 2-hexanone phenylaziridinyl-lEl-hydrazone 127 with LDA and subsequent alkylation with 8-(tert-butyldimethylsilyloxy)octyl bromide gave (Z)-hydrazone 128 in 65% yield. Its LDA-catalyzed selective decomposition followed by hydrolysis of the silyl ether yielded (Z)-9-tetradecen-l-ol, which was acetylated to afford the target compound 129 in 80% yield with a complete regioselectivity and a cisitrans ratio of 99.6/0.4. 

Use of a large, lipophilic nitrogenous component results in a 1idocaine like, local anesthetic type cardiac anti-arrhythmic drug, lorcainide (20). Synthesis begins with the Schiff s base (1 ) derived by reaction of p-chloro-aniline and borohydride followed by acylation with phenyl acetyl chloride produces amide 1 . Selective hydrolysis with HBr followed by alkylation with isopropyl bromide completes the synthesis of lorcainide (20). ... 

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