Nitrile from aldoximes

Synthesis of nitriles from aldoxime with aldoxime dehydratase ... 

The dehydration reaction of aldoxime to form nitriles using the resting cells of Rhodococcus sp. YH3-3 was optimized. We found that the enzyme was induced by aldoxime and catalyzed the stoichiometric synthesis of nitriles from aldoximes at pH 7.0 and 30°C. Phenylacetonitrile once synthesized from phenylacetaldoxime was hydrolyzed to phenylacetic acid, since the strain has nitrile degradation enzymes such as nitrile hydratase and amidase. We have been successful in synthesizing phenylacetonitrile and other nitriles stoichiometrically by a selective inactivation of nitrile hydratase by heating the cells at 40°C for 1 h. Various nitriles were synthesized under optimized conditions from aldoximes in good yields. 

The NHase responsible for aldoxime metabolism from the i -pyridine-3-aldoxime-degrading bacterium, Rhodococcus sp. strain YH3-3, was purified and characterized. Addition of cobalt ion was necessary for the formation of enzyme. The native enzyme had a Mr of 130000 and consisted of two subunits (a-subunit, 27 100 (3-subunit, 34500). The enzyme contained approximately 2 mol cobalt per mol enzyme. The enzyme had a wide substrate specificity it acted on aliphatic saturated and unsaturated as well as aromatic nitriles. The N-terminus of the (3-subunit showed good sequence similarities with those of other NHases. Thus, this NHase is part of the metabolic pathway for aldoximes in microorganisms. 

Many different reagents and conditions have been reported to produce nitriles from aldoximes. This conversion is very much expected under the presence of dehydrating agents, proton or Lewis acid and is independent of the oxime geometry. 

The formation of nitriles from aldoximes was at that time a well-known reaction, at least in its general lines. Gabriel and Meyer found that o-nitrobenzonitrile was obtained by heating o-nitrobenzaldoxime, prepared in an indirect way, with sodium acetate and acetic anhydride Lach prepared benzonitrile in a similar way, and Dollfuss transformed aldoximes of the aliphatic series into nitriles by simple treatment with acetic anhydride. The complicated character of this reaction was demonstrated by the classical work of Beckmann and Hantzsch, who... 

Nitriles from aldoximesThe Vilsmeier reagent reacts with ketoximes to form the O-formate, but converts aldoximes into nitriles in excellent yields. 

The yield of nitriles from aliphatic aldoximes under suitable conditions (reaction time 1-5 hr, KOH 0.1-0.3 mol per 1 mol of aldoxime) can attain 92% (76IZV690). At 140°C under the same conditions, benzaldoxime converts to benzamide in 25% yield. 

Kato, Y, Tsuda, T., and Asano, Y. 1999. Nitrile hydratase involved in aldoxime metabolism from Rhodococcus sp. strain YH3-3. European Journal Biochemistry, 263 662-70. 

The adducts derived from aldoximes and carbodiimides are not stable. They undergo dissociation to give nitriles 472. This reaction is a useful synthetic route to produce nitriles from aldehydes and hydroxylamine in the presence of DCC and cupric salts in one step. The reaction of of the oximes with carbodiimides is best conducted in a two phase system (methylenechloride/water) using triethylamine, and the yields are almost quantitative." ... 

Nitriles from aldoxlmes. The system trifluoroacetic anhydride and pyridine, which converts primary amides to nitriles, also converts aldoximes to nitriles. The geometrical configuration of the substrate determines the ease of dehydration (E)-Aldoximes are less reactive than (Z)-aldoximes. However, high yields can also be obtained from the former substrates if the amount of pyridine is increased or if the reaction is conducted at higher temperatures (60-65°). 

Nitriles from aUoximes. Aliphatic, aromatic, and olefinic aldoximes (1 mole) are dehydrated by treatment with triethylamine (3 moles), and phosphonitrilic chloride (1 mole) in ether or THF at room temperature for 8 24 hr. yields are in the range 70-95%. 

Aldoximes derived from an o-protected vanillin 321, when treated with TCCA in the presence of olefins as dipolarophiles, afford nitrile oxides 322. Subsequent 1,3-dipolar cycloaddition generates the corresponding isoxazo-lines 323 (Scheme 72) <2001SC3075>. 

A mixture of N-p-tolyldiphenylacetamide and hexamethylcyclotrisilazane heated 4 hrs. at 240 diphenylacetonitrile. Y 73%. - The dioice of silazanes, chloro-silanes, or alkoxysilanes allows the reaction to be run under mildly basic, acidic, or neutral conditions. If the former reagents are used, the reaction may be followed by NH3- or HCl-liberation respectively. The products can be easily isolated by distillation if volatile or by filtration if solid. F. e., also from unsubst. amides and aldoximes, and f. silicon compds. as reagents, s. W. E. Dennis, J. Org. Chem. 35, 3253 (1970) nitriles from unsubst. amides with hexamethylphosphor-amide s. R. S. Monson and D. N. Priest, Can. J. Chem. 49, 2897 (1971). 

M ethane sul forty I chloride/pyridine Nitriles from aldoximes... 

Spenser and Ahmad (81, 92) found that disproportionation of N-hydroxyamino acids (27) occurs in aqueous solution. The keto acid oxime (31) decompose further to give the corresponding nitrile (33) (93) (Scheme 6). The above results are questionable as Steiger (94) and Moller et al. (95) obtained amino acids and the corresponding aldoximes (36) from aromatic N-hydroxyamino acids (34) and (35) (Scheme 7). 

Sodium hydroxylaminedisulfonate Nitriles from aldehydes via aldoximes... 

Chlorosulfonyl isocyanate, Cl-S02-N=00, is an effective dehydrating agent for the preparation of various aryl- and alkyl-nitriles from the corresponding amides and aldoximes in yields of 74-87% and 75-86%, respectively [1128],... 

General procedure. Nitriles from aldoximes [1128] To a magnetically stirred solution of the aldoxime (10 mmol) and dry triethylamine (20 mmol) in dry dichloro-methane (10 mL), a solution of chlorosulfonyl isocyanate (15 mmol) in dichloro-methane (10 mL) is added at 0 °C. The reaction mixture is stirred for 8 h at room temperature and then poured into water (caution ). The dichloromethane layer is separated and the aqueous layer is extracted with dichloromethane (3 x 25 mL). The organic layers are combined, washed with water, and dried over anhydrous sodium sulfate. Evaporation of the solvent gives the nitriles, which are purified by distillation or recrystallization. 

In an aqueous medium, hydrolysis proceeds faster than dehydration because water is in large excess. However, in some cases, dehydration is preferred over hydrolysis. Remarkable results were reported by Kato et al. (Fig. 10.34), who demonstrated that aldoxime dehydratase from Bacillus sp. efficiently converted aldoximes into the corresponding nitriles in water. ... 

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