Hydrolysis, acetal oxime

In addition to the acid-catalysed hydrolysis of oximes, a kinetic study has also been made of the addition of bromine to a number of substituted benzal-dehyde phenylhydrazones . The measurements were made in 70% acetic acid v/v, in the presence of 0.1 M potassium bromide. The attacking species was shown to be predominantly molecular halogen, and not the tribromide ion, since a graph of 2(1 -t- X[Br ]) against [Br ] was linear, and of zero intercept, k-2 being defined by the equation... 

Acetal 136 on enolization followed by conjugate addition with nitro olefin 122 gave alkylated products 137 and 138 in a diastereomeric mixture of 10 1. Compound 137 was proceeded for amathaspiramide F synthesis, which on hydrolysis followed by N-trifluoroacetyl protection gave amide 139. Nitro group of compound 139 was converted into oxime 140. Hydrolysis of oxime followed by cyclization and then deprotection of N-trifluoroacetyl group gave amathaspiramide F (134) Scheme 12 [63],... 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

This method is an adaptation of that of Dengel. -Methoxy-phenylacetonitrile can also be prepared by the metathetical reaction of anisyl chloride with alkali cyanides in a variety of aqueous solvent mixtures by the nitration of phenylaceto-nitrile, followed by reduction, diazotization, hydrolysis, and methylation 1 by the reduction of ct-benzoxy- -methoxy-phenylacetonitrile (prepared from anisaldehyde, sodium cyanide, and benzoyl chloride) and by the reaction of acetic anhydride with the oxime of -methoxyphenylpyruvic acid. ... 

Base-catalyzed fragmentation also occurs on treatment of 5,6j9-epoxy-19-aldehyde (hemiacetal, hemiacetal-acetate or 3)5,6/ -acetal) accessible from nitrous acid-acetic acid treatment of 5a-bromo-6jS-hydroxy-19-oximes followed by mild base hydrolysis (yield not reported)... 

An artificial metalloenzyme (26) was designed by Breslow et al. 24). It was the first example of a complete artificial enzyme, having a substrate binding cyclodextrin cavity and a Ni2+ ion-chelated nucleophilic group for catalysis. Metalloenzyme (26) behaves a real catalyst, exhibiting turnover, and enhances the rate of hydrolysis of p-nitrophenyl acetate more than 103 fold. The catalytic group of 26 is a -Ni2+ complex which itself is active toward the substrate 1, but not toward such a substrate having no metal ion affinity at a low catalyst concentration. It is appearent that the metal ion in 26 activates the oximate anion by chelation, but not the substrate directly as believed in carboxypeptidase. 

Oxime carbamates have high polarity and solubility in water and are relatively chemically and thermally unstable. They are relatively stable in weakly acidic to neutral media (pH 4-6) but unstable in strongly acidic and basic media. Rapid hydrolysis occurs in strongly basic aqueous solutions (pH > 9) to form the parent oxime/alcohol and methylamine, which is enhanced at elevated temperature. Additionally, oxime carbamates are, generally, stable in most organic solvents and readily soluble in acetone, methanol, acetonitrile, and ethyl acetate, with the exception of aliphatic hydrocarbons. Furthermore, most oxime carbamates contain an active -alkyl (methyl) moiety that can be easily oxidized to form the corresponding sulfoxide or sulfone metabolites. 

Methyl-2-cyclohexenone has been prepared (a) by the action of ni-t rosyl chloride on 1-methylcydohexene, followed by dehydrohalogena-I ion with sodium methoxide4 or sodium acetate,6 and hydrolysis of the resulting oxime (b) in an impure condition by several methods 6-12... 

On treatment with dimethyl sulfoxide-acetic anhydride followed by sequential oximation, reduction, detritylation, and acid hydrolysis, a tetra-(6-0-trityl)-cyclohexaamylose was reported to afford 2-amino-2-deoxy-D-glucose, in addition to D-glucose, indicating459 that... 

Several 4-(3-alkyl-2-isoxazolin-5-yl)phenol derivatives that possess liquid crystal properties have also been obtained (533-535). In particular, target compounds such as 463 (R = pentyl, nonyl) have been prepared by the reaction of 4-acetoxystyrene with the nitrile oxide derived from hexanal oxime, followed by alkaline hydrolysis of the acetate and esterification (535). A homologous series of 3-[4-alkyloxyphenyl]-5-[3,4-methylenedioxybenzyl]-2-isoxazolines, having chiral properties has been synthesized by the reaction of nitrile oxides, from the dehydrogenation of 4-alkyloxybenzaldoximes. These compounds exhibit cholesteric phase or chiral nematic phase (N ), smectic A (S4), and chiral smectic phases (Sc ), some at or just above room temperature (536). 

Aldosterone Aldosterone, llj3,21-dihydroxypregn-4-en-2,18,20-trione (27.2.4), is synthesized from 21-0-acetylcorticosterone, which when reacted with nitrosyl chloride in pyridine gives the nitrite 27.2.1. When photochemically irradiated, this compound is transformed to the oxime 27.2.2, which is hydrolyzed by nitrous acid and forms the semiacetal 27.2.3, which is an acetate of the desired aldosterone. Alkaline hydrolysis of the acetyl group of this compound leads to the desired aldosterone (27.2.4) [33]. 

D-Fucose (Rhodeose). Voto6ek obtained tetraacetyl-D-fucononitrile in 25% yield by treating D-fucose oxime with sodium acetate-acetic anhydride. The nitrile, degraded with ammonia and silver oxide, yielded 5-desoxy-D-lyxose diacetamide in 40% yield. The diacetamide compound was hydrolyzed with 5% hydrochloric acid and the 5-desoxy-D-lyxose was obtained in solution and characterized as the p-bromo-phenylosazone. Hydrolysis of the diacetamide compound with 6 N sulfuric acid was realized by Voto6ek and Valentin and the 5-desoxy-D-lyxose was isolated as a sirup. 

A related sequence was used by Kozikowski and Park (74) to prepare the ring skeleton of streptazolin (200), a compound that exhibits antibacterial and antifungal effects. In this approach, the tricyclic isoxazoline intermediate 198 was formed in the key cycloaddition step (Scheme 6.86). Thus, the reaction of oxime 197 (obtained from 4-piperidone) with sodium hypochlorite-triethylamine afforded tricyclic isoxazoline 198 in very good yield. This cycloadduct was converted to p-hydroxyketone 199 by reduction/hydrolysis using Raney Ni in the presence of acetic acid. Racemic streptazolin (200) was obtained from 199 in several additional steps (74). 

The product (15-2) from aldol condensation of meto-nitrobenzaldehyde with the dimethyl acetal from ethyl 4-formylacetoacetate (15-1) provides the starting material for a dihydropyridine in which one of the methyl groups is replaced by a nitrile. Reaction of (15-2) with the eneamine from isopropyl acetoacetate gives the corresponding dihydropyridine hydrolysis of the acetal function with aqueous acid affords the aldehyde (15-3). That function is then converted to its oxime (15-4) by reaction with hydroxylamine. Treatment of that intermediate with hot acetic acid leads the oxime to dehydrate to a nitrile. There is this obtained nilvadipine (15-5) [16]. 

The dibasic side chain at position 7 can be alternatively provided by a substituted amino alkyl pyrrolidine. Preparation of that diamine in chiral form starts with the extension of the ester function in pyrrolidone (46-1) by aldol condensation with ethyl acetate (46-2). Acid hydrolysis of the (3-ketoester leads to the free acid that then decarboxylates to form an acetyl group (46-3). The carbonyl group is next converted to an amine by sequential reaction with hydroxylamine to form the oxime, followed by catalytic hydrogenation. The desired isomer (46-4) is then separated... 

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