Nitrile groups, hydrolysis

Nitrile groups m cyanohydrins are hydrolyzed under conditions similar to those of alkyl cyanides Cyanohydrin formation followed by hydrolysis provides a route to the preparation of a hydroxy carboxylic acids... 

In the Strecker synthesis an aldehyde is converted to an a ammo acid with one more carbon atom by a two stage procedure m which an a ammo nitrile is an mterme diate The a ammo nitrile is formed by reaction of the aldehyde with ammonia or an ammonium salt and a source of cyanide ion Hydrolysis of the nitrile group to a car boxylic acid function completes the synthesis... 

Physical properties for naphthalene mono-, di-, tri-, and tetracarboxyhc acids are summari2ed in Table 9. Most of the naphthalene di- or polycarboxyLic acids have been made by simple routes such as the oxidation of the appropriate dior polymethylnaphthalenes, or by complex routes, eg, the Sandmeyer reaction of the selected antinonaphthalenesulfonic acid, to give a cyanonaphthalenesulfonic acid followed by fusion of the latter with an alkah cyanide, with simultaneous or subsequent hydrolysis of the nitrile groups. 

Nitrile Group. Hydrolysis of the nitrile group proceeds through the amide to the corresponding carboxyUc acid. Because cyanohydrins are unstable at high pH, this hydrolysis must be cataly2ed by acids. In cases where amide hydrolysis is slower than nitrile hydrolysis, the amide may be isolated. 

Deuterium labeling of C-18 has also been accomplished by an alternate procedure adapted from the Nagata steroid synthesis. During the course of the total synthesis of pregnanolone, thevC-18 function is introduced in the form of a nitrile group. Reduction of this function in intermediate (247) with lithium aluminum deuteride leads to a deuterated imine (248), which upon Wolff-Kishner reduction and acid-catalyzed hydrolysis... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

These copolymers undergo side reactions which are mainly reducible to reactions in which chloride atoms take part. When copolymers of AN and vinylidene chloride are treated with aqueous solutions of ammonium sulfide at 90 °C, nitrile groups have been shown to be almost fully converted into thioamide groups, and practically no hydrolysis of the formed thioamide groups is taking place in this case. At the same time, it was found that in the course of this treatment dehydrochlorination is taking place almost quantitatively ... 

The reaction proceeds via die hydrolysis of nitrile groups to an amide. The amides may also be A-formyl amines, which react with acid groups whereby volatile formic acid is shipped10 ... 

Bromo-5,6,7,8-tetrahydro-2-quinoxahnecarbonitrile (131) gave the 3-methoxy analog (132) (NaOH, MeOH, 20°C, 2h 90%) and thence 3-oxo-3,4,5,6,7,8-hexahydro-2-quinoxalmecarbonitrile (133) (Nal, MesSiCl, MeCN, 20°C, 6h 91%) this gentle indirect hydrolysis was clearly adopted to avoid hydrolysis of the nitrile group). ... 

The biocatalytic differentiation of enantiotopic nitrile groups in prochiral or meso substrates has been studied by several research groups. For instance, the nitrilase-catalyzed desymmetrization of 3-hydroxyglutaronitrile [92,93] followed by an esterification provided ethyl-(Jl)-4-cyano-3-hydroxybutyrate, a useful intermediate in the synthesis of cholesterol-lowering dmg statins (Figure 6.32) [94,95]. The hydrolysis of prochiral a,a-disubstituted malononitriles by a Rhodococcus strain expressing nitrile hydratase/amidase activity resulted in the formation of (R)-a,a-disubstituted malo-namic acids (Figure 6.33) [96]. 

There are two pathways for the degradation of nitriles (a) direct formation of carboxylic acids by the activity of a nitrilase, for example, in Bacillus sp. strain OxB-1 and P. syringae B728a (b) hydration to amides followed by hydrolysis, for example, in P. chlororaphis (Oinuma et al. 2003). The monomer acrylonitrile occurs in wastewater from the production of polyacrylonitrile (PAN), and is hydrolyzed by bacteria to acrylate by the combined activity of a nitrilase (hydratase) and an amidase. Acrylate is then degraded by hydration to either lactate or P-hydroxypropionate. The nitrilase or amidase is also capable of hydrolyzing the nitrile group in a number of other nitriles (Robertson et al. 2004) including PAN (Tauber et al. 2000). 

Incompatibility of the nitrile group with the oxidative work-up of the L-Selectride reduction using basic hydrogen peroxide Significant hydrolysis to the primary amide with concomitant exothermic activity and loss of product... 

DTA examination of a 35% solution of the diazonium salt in sulfuric acid showed 3 exotherms, corresponding to hydrolysis of the nitrile group (peak at 95°), decomposition of the diazonium salt (peak at 160°) and loss of the nitro group (large peak at 240°C). Adiabatic decomposition of the solution from 50°C also showed 3 steps, with induction periods of around 30, 340 and 380 min, respectively. 

Since the hybridization and structure of the nitrile group resemble those of alkynes, titanium carbene complexes react with nitriles in a similar fashion. Titanocene-methylidene generated from titanacyclobutane or dimethyltitanocene reacts with two equivalents of a nitrile to form a 1,3-diazatitanacyclohexadiene 81. Hydrolysis of 81 affords p-ketoena-mines 82 or 4-amino-l-azadienes 83 (Scheme 14.35) [65,78]. The formation of the azati-tanacyclobutene by the reaction of methylidene/zinc halide complex with benzonitrile has also been studied [44]. 

Substituted thioindigoid dyes are usually obtained via the appropriate benzenethiol in a Heumann-type synthesis. The final cyclisation of the phenylthioglycolic acid derivative can often be achieved in concentrated sulphuric acid or by using chlorosulphonic acid. Several routes make use of the Herz reaction (Scheme 6.22), in which a substituted aniline is converted into the corresponding o-aminothiophenol by reaction with sulphur monochloride followed by hydrolysis of the intermediate dithiazolium salt [47]. After reaction between the thiol and chloroacetic acid, the amino group is converted into a nitrile group by a Sandmeyer reaction. Hydrolysis of the nitrile leads to the formation of the required thioindoxyl derivative. 

A synthesis of great industrial interest is the electrochemical anodic reductive dimerisation of two molecules of acrylonitrile to give adiponitrile, from which adipic acid and 1,6-hexanediamine are prepared by hydrolysis and reduction, respectively, of the two nitrile groups. Polycondensation of the resulting products leads to Nylon 66 (Scheme 5.27). 

Chemical/Physical. In laboratory tests, the nitrile group was hydrolyzed to the corresponding carboxylic acid. The rate of hydrolysis is faster at higher temperatures and low pHs (Grayson, 1980). The chlorine atom may be replaced by a hydroxyl group forming 2((4-hydroxy-6-(ethyl-amino)-5-triazin-2-yl)amino)-2-methylpropanenitrile (Hartley and Kidd, 1987). 

Cyanohydrin formation is a useful synthetic reaction, in that it utilizes a simple reagent, cyanide, to create a new C-C bond. The cyano (nitrile) group may easily be modified to other functions, e.g. carboxylic acids via hydrolysis (see Box 7.9) or amines by reduction. 

Glutethimide Glutethimide, 2-ethyl-2-phenylgutarimide (4.3.6), is synthesized by addition of 2-phenylbutyronitrile to the methylacrylate (Michael reaction), and the subsequent alkaline hydrolysis of the nitrile group in the obtained compound (4.3.5) into an amide group, and the subsequent acidic cycUzation of the product into the desired glutethimide (4.3.6) [38-42]. 

Doxapram Doxapram, l-ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone (8.2.4), is synthesized in the following manner. Diphenylacetonitrile in the presence of sodium amide is alkylated with l-ethyl-3-chlorpyrrolidine, giving (l-ethyl-3-pyrrolidinyl) diphenylacetonitrile (8.2.1). Acidic hydrolysis of the nitrile group gives (l-ethyl-3 pyrrolidinyl)diphenylacetic acid (8.2.2). Reacting this with phosphorous tribromide... 

Isopropamide Isopropamide, (3-carbamoyl-3,3-diphenylpropyl)di-tiO-propylmethyl ammonium iodide (14.1.25), is synthesized by alkylating diphenylacetonitrile with di-/io-propylaminoethylchloride in the presence of sodium amide, and the subsequent hydrolysis of the nitrile group of the resulting compound (14.1.23) to an amide group (14.1.24). Alkylation of this compound with methyliodide gives isopropamide (14.1.25) [19-22]. 

When a Wohl degradation is carried out in the laboratory, hydrolysis of the acyl and nitrile groups begins immediately upon addition of ammonia. The rate of hydrolysis of each of the groups present in the molecule is probably different and at the present time we have no knowledge of these rates of hydrolysis. As Hockett and Chandler have pointed out, the diacetamides are obviously formed as a result of a delicate balance among the rates of several concurrent reactions. ... 

Removal of the acetyl and nitrile groups by acid hydrolysis was also achieved by Wohl, who isolated a pentosazone from the products from heating pentaacetyl-D-glucononitrile with 2 N hydrochloric acid. Fischer also isolated what is now known to have been a 5-desoxy-L-arabinosazone from the products obtained by treatment of tetraacetyl-L-rhamnononitrile with 5% hydrochloric acid. At the same time partial transformation of the nitrile into the aldonic acid takes place as shown by Maquenne, who obtained D-xylonic acid by treating tetraacetyl-D-xylononitrile with concentrated hydrochloric acid. 

Deulofeu also degraded tetraacetyl-D-arabononitrile with sodium methoxide or by hydrolysis of the acetyl groups with sulfuric acid and separation of the nitrile group with silver carbonate. D-Erythrose was characterized as the phenylosazone. 

Generally, enzymatic hydrolysis of nitriles to the corresponding acids can either proceed stepwise, which is the case for catalysis by the nitrile hydratase/amidase enzyme system, or in one step in the case of nitrilases. Both systems have been investigated for surface hydrolysis of PAN [10], Complete hydrolysis with either system was monitored by quantification of ammonia and/or polyacrylic acid formed as a consequence of hydrolysis of nitrile groups [70-72], As a result, considerable increases in colour levels (e.g. 156% for commercial nitrilase) were found upon dyeing [72],... 

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