Nitriles functional derivatives

Catalytic hydrogenation of the nitrile function of cyanohydrins can give amines. As in the case of ordinary nitriles, catalytic reduction of cyanohydrins can yield a mixture of primary, secondary, and tertiary amines. Addition of acid or acetic anhydride to the reaction medium minimizes formation of secondary or tertiary amines through formation of the amine salt or acetamide derivative of the primary amine. 

The most interesting aminomethyl derivative of condensation polymers that we have prepared to date Is derived from direct reduction of poly(2-cyano-l,3-phenylene arylene ether), 20. Enchainment of benzonitrile repeat units Is accomplished by coupling 2,6-dichlorobenzonitrile with the potassium salt of bisphenol-A copolymers with lower nitrile contents can be produced by copolycondensation of bisphenol-A, 2,6-dichlorobenzonitrile and 4,4 -dichlorodiphenyl sulfone.21 The pendent nitrile function provides an active site for further elaboration. 

Cycloaddition with nitrile oxides occur with compounds of practically any type with a C=C bond alkenes and cycloalkenes, their functional derivatives, dienes and trienes with isolated, conjugated or cumulated double bonds, some aromatic compounds, unsaturated and aromatic heterocycles, and fullerenes. The content of this subsection is classified according to the mentioned types of dipolarophiles. Problems of relative reactivities of dienophiles and dipoles, regio- and stereoselectivity of nitrile oxide cycloadditions were considered in detail by Jaeger and... 

Taylor and Patel describe a quinazoline synthesis (Scheme 93) transforming the iminophosphorane of anthranonitrile with isocyanate to car-bodiimide 254. Addition of ammonia in tetrahydrofuran (THF) leads to guanidine 255, which affords with the adjacent nitrile function quinazoline derivatives 256 (91JHC1857). 

Carrie and co-workers studied the cycloaddition of oxime esters derived from methyl cyanoacetate and malonate esters 82 (Scheme 8.20) with diazomethane and some monosubstituted derivatives. Thermally labile 1,2,3-triazolines 83 were obtained when tosyloxy- and benzoyloxyimines were used (141), while methyl acetoxyimino-cyanoacetate (82, X = CN, Y = C02Me, = Ac) gave products derived from both a 1,2,3- and a 1,2,4-triazoline, depending on the stmcture of the diazo compound (142). Not unexpectedly, diazomethane reacted with the corresponding imino-malononitrile (82, X = Y = CN) system at the nitrile function rather than at the C=N bond (143). 

Grogan et al. [8] provided a relevant example and discussed how to derive and use a QSAR equation for purposes of predicting acute lethality of nitriles and designing chemicals that have nitrile functionality (i.e., contain a cyano moiety) to be of minimal toxicity. This QSAR is illustrated by... 

The addition of unstabilized a-nitrile carbanions to a,3-unsaturated carbonyl acceptors affords predominantly 1,2-addition products, 56 while lithiated acetonitrile derivatives having a-alkoxy, a-aromatic, a-dialkylamino, a-phenylselenyl, a-phenylthio or a-trimethylsilyl substituents afford 1,4-adducts. However, some of these are acyl anion equivalents (Section 1.2.2.3.2) so this discussion is limited to a-stabi-lized nitriles in which the nitrile function is retained after removal of the activating group. Notable examples are trimethylsilylacetonitrile (208),157 phenylthioacetonitriles (209),158a b phenylselenylacetoni-... 

This above result was only obtained with maleimide as the dipolarophile. With dimethyl fumarate and fumaronitrile, A2-pyrrolines are obtained, probably because of the acidity of the hydrogen atoms a- to ester and nitrile functionalities. Reaction with alkynes produces pyrrole derivatives in good to excellent yields and with aromatic aldehydes leads regioselectively to oxazolidines in moderate yields.263... 

Where R4 is a hydrogen or carbon atom, 10.15 is simply an amidine. However, urea 10.16, thiourea 10.17, or guanidine 10.18 and their derivatives may be used. These nucleophiles may be condensed with ester and nitrile functionalities as well as with aldehydes and ketones. Such condensations to afford pyridimidine derivatives are usually facilitated by acid or base catalysis, although certain combinations of reactive electrophilic and nucleophilic compounds require no catalyst at all. Some examples are shown below. 

Substituted derivatives of type (105) have been reported to undergo cleavage in the presence of acid to yield the acetic acid derivative (106 Scheme 48) (65AHC(5)119). The nitrile functions of the isomeric compounds (107) and (108) have been converted into the corresponding amides, carboxylic acids and methyl esters in the usual fashion (81JOC771). 

Several new routes involve formation of one carbon-carbon bond in pre-formed substrates. Palladium-catalyzed cyclization of /3-hydroxyenamine derivatives has been employed in a route to substituted pyrroles and 4,5,6,7-tetrahy-droindoles with multiple substituents by formation of the C-3-C-4 bond as the key feature, as illustrated by construction of the molecule 534 (Equation 146) <2006T8533>. Zinc perchlorate-catalyzed addition of alcohols to the nitrile functionality of a-cyanomethyl-/3-ketoesters, followed by annulation gave access to a series of substituted ethyl 5-alkoxypyrrole-3-carboxylates <2007T461>. Similar chemistry has also been used for synthesis of a related set of pyrrole-3-phosphonates <2007T4156>. A study on preparation of 3,5,7-functionalized indoles by Heck cyclization of suitable A-allyl substituted 2-haloanilines has also appeared <2006S3467>. In addition, indole-3-acetic acid derivatives have been prepared by base induced annulation of 2-aminocinnamic acid esters (available for instance from 2-iodoani-lines) <2006OL4473>. 

Because cyanoethylated wood contains reactive nitrile groups, various functional derivatives are obtained by utilizing the nitrile groups [25]. For example, carbamoylethylated wood (water-soluble, nonionic, liquid crystal-... 

Oxidation of the Schiff bases (19) made from the monoamide of DAMN (derived from DAMN by hydration of one of the nitrile functions) gives 4-cyanoimidazole-5-carboxamides (20) in good yields ( 70% or more) (Scheme 2.1.7). Such oxidations can be readily accomplished using hydrogen peroxide with a catalytic amount of sodium molybdate fSl]. 

A functional derivative of penicillin amide is the nitrile (71) [104], the activity of which is even lower. 

With dimethylacetylene dicarboxylate (DMAD) 1-acylimidazoles form novel functionalized derivatives as a consequence of electrophilic attack on the pyridine nitrogen followed by intramolecular transacylation (Scheme 112) <88CC1151,90JCS(P1)1821,92CB1939>. Ketoximes undergo Beckmann rearrangement and primary carboxamides are dehydrated to nitriles on treatment with (170)... 

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