Nitriles amine addition

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. 

Other dimer acid markets include intermediates for nitriles, amines and diisocyanates. Dimers are also used in polyurethanes, in corrosion inhibition uses other than for downweU equipment, as a "mildness" additive for metal-working lubricants, and in fiber glass manufacture. 

Regio- and enantio-selective additions of nitrile amines (R1-C=N+-N--R2, from the hydrazonyl bromide) to enones allows access to dihydropyrazoles close to enantiop- urity, via a 3 + 2-cycloaddition.65... 

The mobile phases used in normal-phase chromatography are based on nonpolar hydrocarbons, such as hexane, heptane, or octane, to which is added a small amount of a more polar solvent, such as 2-propanol.5 Solvent selectivity is controlled by the nature of the added solvent. Additives with large dipole moments, such as methylene chloride and 1,2-dichlor-oethane, interact preferentially with solutes that have large dipole moments, such as nitro- compounds, nitriles, amines, and sulfoxides. Good proton donors such as chloroform, m-cresol, and water interact preferentially with basic solutes such as amines and sulfoxides, whereas good proton acceptors such as alcohols, ethers, and amines tend to interact best with hydroxylated molecules such as acids and phenols. A variety of solvents used as mobile phases in normal-phase chromatography are listed in Table 2.2, some of which may need to be stabilized by addition of an antioxidant, such as 3-5% ethanol, because of the propensity for peroxide formation. 

Various modifications of the reaction of an alcohol with ammonia provide the most common commercial routes to alkylamines. Some others routes that are used to make certain individual amines include aldehyde/amine additions, nitrile reduction, the Ritter reaction, amination of isobutylene, and hydrogenation of anilines. Capacities of many plants depend on the product mix of mono/di/tri products as well as the variety of amines (ethyl, propyl and butyl). One must know the product mix that the capacity is based upon and the actual scheduled output of produces) to determine what amounts can actually be manufactured. Capacities are often in excess of anticipated demand to satisfy seasonal demands for pesticide uses116. 

Cavell investigated the reactivity of 132 and 133 towards a wide range of substrates including THF, nitriles, iso-nitriles, amines, alcohols, alkyl halides, carbon dioxide, isocyanates, and carbodiimides. Three classes of reactivity emerged (i) base adduct formation (ii) 1,2-addition across the M=C bond (iii) [2 + 2] cycloadditions across the M=C double bond.62,63... 

C3H9N [107-10-8]), and the industrially important hydrodimerization to produce adiponitrile (C6HgN2 [111-69-3 f) (25—27). Other reactions include addition of halogens across the double bond to produce dihalopropionitriles, and cyanoetliylation by acrylonitrile of alcohols, aldehydes, esters, amides, nitriles, amines, sulfides, sulfones, and halides. 

Dideoxynucleosides show potent anti-retroviral activity against HIV-specific reverse transcriptase80-83. In particular, 2, 3 -dideoxy-3 -C-cyano-2 -substituted thymidine derivatives (33 A and 33 B) with a free 5 -hydroxy function (R1 = H) are potential inhibitors of the HIV-reverse transcriptase-promoted c-DNA synthesis. As these compounds have yet to be prepared by another method, the 3 -ene-nitrile 3284 was subjected to conjugate addition reactions with ammonia, primary amines, secondary amines and carbon nucleophiles. Most of these nucleophilic amine addition reactions give either the trans-isomer 33 A as the sole product (e.g., reaction with pyrrolidine, piperidine, morpholine), or as the major product along with the c/s-isomer (e.g., reaction with methylamine, benzylamine), except for the reaction with ammonia where the cts-isomer 33B is formed as the major product84. 

Common functional groups that contain nitrogen atoms are also distinguishable by their IR absorptions above 1500 cm , as illustrated by the IR spectra of an amine (octylarnine), an amide (propanamide), and a nitrile (octanenitrile). Additional details on the IR spectra of these compounds are given in Chapters 22 and 25. 

Addition of Alcohols, Water, and Amines. In general, additions to nitriles resemble additions to carbonyl groups with the exception that the primary addition products of simple molecules such as alcohols, water, and ammonia result in the formation of somewhat more stable compounds. Alcohols, for example, react with nitriles in the presence of an acidic catalyst to form salts of imino ethers ... 

Noteworthy was the increase of the selectivity in water toward the 1 1 adduct when using nitromethane. Under slightly alkaline conditions, cetyltrimethylam-monium chloride was shown to catalyze the addition of various nitroalkanes onto conjugated enones [176]. Amines also reacted in aqueous Michael additions, especially with a, -unsaturated nitriles [177]. The lack of apparent reactivity of a, -unsaturated esters comes from the reverse reaction which is particularly accelerated in water. In these amine additions, water activation was compared with high pressure giving support to the implication of the hydrophobic effect. A related reaction is the Baylis-Hillman reaction which proceeds readily in water with a good rate enhancement (Scheme 34) [178]. 

The ease of reaction depends both on the CH acidity of the addend and on the polarizability of the ethylenic double bond of the acceptor. Thus, in general, only such compounds function as addend in which a methylene or methine group is activated by two neighboring carbonyl or nitrile groups, as, for example, in malonic esters, malonodinitrile, cyanoacetic esters, 1,3-dioxo compounds and 3-oxo carboxylic esters, and their monoalkyl substitution products. The ethylenic double bond of the acceptor is polarized by conjugation with a polar multiple bond, so that the olefinic component is usually an unsaturated ketone, an, / -unsaturated ester, or an, / -unsaturated nitrile. The addition is catalysed by bases such as potassium hydroxide solution, sodium ethoxide, and amines. 

One possible synthesis of the TM begins with the reaction of 2-bromobutane with NaCN. Hydride reduction of the resulting nitrile affords 2-methylbutan-1-amine. Addition of benzoyl chloride and reduction of the resulting amide product installs the second alkyl group on the secondary amine TM. 

Addition to C=N Allylic amination Amides from aldehydes Amides from nitriles Aminals from aldehydes Amination of aryl halides a - Aminoallylation Aminocarbonylation Aminohydroxylation Arylation... 

Cyclitols have been used as chiral auxiliaries for nitrile oxide additions to acrylates,and chiral azomethine ylides, for example 130 and 131, have been used for the asymmetric synthesis of pyrrolidines ylide generation involves treatment of a tertiary amine N-oxide with LDA. ... 

A variety of other methods have been employed on a case-by-case basis to effect auxiliary cleavage, and a detailed account of these methods is available. In addition to hydrolytic approaches, for aldehyde hydrazones, a number of convenient direct methods are available that allow the auxiliary to be cleaved in such a way that a functional group other than an aldehyde is generated. For instance, aldehyde-derived SAMP/RAMP hydrazones can be directly converted into the corresponding nitriles, ° amines,or dithianes, thereby enabling subsequent reactivity not immediately available from the aldehyde itself (Scheme 7.5). 

Allylic amine is a less reactive leaving group[7], but the allylic ammonium salts 214 (quaternary ammonium salts) can be used for allylalion(l30,131]. Allylic sulfonium salts are also used for the allylation[130]. The allylic nitrile in the cyclic aminonitrile 215 can be displaced probably via x-allylic complex formation. The possibility of the formation of the dihydropyridinium salts 216 and subsequent conjugate addition are less likelyfl 32],... 

Cycloahphatic amine synthesis routes may be described as distinct synthetic methods, though practice often combines, or hybridi2es, the steps that occur amination of cycloalkanols, reductive amination of cycHc ketones, ring reduction of cycloalkenylarnines, nitrile addition to ahcycHc carbocations, reduction of cyanocycloalkanes to aminomethylcycloalkanes, and reduction of nitrocycloalkanes or cycHc ketoximes. 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

In addition to the nitrile and alcohol routes for fatty amine preparation, processes have been described by Unocal and Pennwalt Corporation, using an olefin and secondary amine (14—16) by Texaco Inc., hydrogenation of nitroparaffins (17—20) by Onyx Corporation, reaction of an alkyl haUde with secondary amines (21,22) by Henkel Cie, GmbH, reduction of an ester in the presence of a secondary amine (23) by catalytic hydroammonolysis of carboxyhc acids (24) and by the Hofmann rearrangement (25). 

Nitrile Intermediates. Most quaternary ammonium compounds are produced from fatty nitriles (qv), which are ia turn made from a natural fat or oil-derived fatty acid and ammonia (qv) (Fig. 2) (see Fats AND FATTY oils) (225). The nitriles are then reduced to the amines. A variety of reduciag agents maybe used (226). Catalytic hydrogenation over a metal catalyst is the method most often used on a commercial scale (227). Formation of secondary and tertiary amine side-products can be hindered by the addition of acetic anhydride (228) or excess ammonia (229). In some cases secondary amines are the desired products. 

Additions. The addition reactions of ammonia and amines to the cyanamide nitrile group have been thoroughly studied (15). For optimum conditions, the reaction should be carried out ia an aqueous medium at about 140°C. Gradual addition of the cyanamide to the amine salt minimises dimerization. 

Because nitrile rubber is an unsaturated copolymer it is sensitive to oxidative attack and addition of an antioxidant is necessary. The most common practice is to add an emulsion or dispersion of antioxidant or stabilizer to the latex before coagulation. This is sometimes done batchwise to the latex in the blend tank, and sometimes is added continuously to the latex as it is pumped toward further processing. PhenoHc, amine, and organic phosphite materials are used. Examples are di-Z fZ-butylcatechol, octylated diphenylamine, and tris(nonylphenyl) phosphite [26523-78-4]. All are meant to protect the product from oxidation during drying at elevated temperature and during storage until final use. Most mbber processors add additional antioxidant to their compounds when the NBR is mixed with fillers and curatives in order to extend the life of the final mbber part. 

S-Substituted thiiranium ions react with secondary amines to give ring-opened products. Nitriles also react with thiiranium ions, probably via an open carbenium ion whose formation is favored by increasing the polarity of the medium by the addition of lithium perchlorate (Scheme 79) (79ACR282). An intramolecular displacement by an amide nitrogen atom on an intermediate thiiranium ion has been invoked (80JA1954). 

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