Synthesis nitriles from amines

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

The synthesis of nitriles from halides is valuable in medicinal chemistry because nitriles are flexible building blocks readily converted into carboxylic acids, amides, amines, or a variety of heterocycles, e. g. thiazoles, oxazolidones, triazoles, and tetrazoles. The importance of the tetrazole group in medicinal chemistry is easily understood if we consider that it is the most commonly used bioisostere of the carboxyl group. 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

The conventional procedure for the synthesis of homoallylic amines involves the allylboration of imines (generated in situ from the partial reduction of expensive and toxic nitriles). Recently, a practical and operationally simple protocol has been developed for the stereoselective formation of homoallylic amines starting directly from the... 

For example, N-(2-hydroxyphenyl)imines 9 (R = alkyl, aryl) together with chiral zirconium catalysts generated in situ from binaphthol derived ligands were used for the asymmetric synthesis of a-amino nitriles [17], the diastereo- and/or enantioselective synthesis of homoallylic amines [18], the enantioselective synthesis of simple //-amino acid derivatives [19], the diastereo- and enantioselective preparation of a-hydroxy-//-amino acid derivatives [20] or aminoalkyl butenolides (aminoalkylation of triisopropylsilyloxyfurans, a vinylogous variant of the Mannich reaction) [21]. A good example for the potential of the general approach is the diastereo- and enantioselective synthesis of (2R,3S)-3-phenylisoserine hydrochloride (10)... 

The direct synthesis of aryl- or alkyl nitriles from cyanide and organohalide precursors is revered in synthetic chemistry, as the nitriles represent a flexible functionality that can easily be converted into (for example) carboxylic acids, esters, amides, amidines, amines and various hetero cycles [67], such as thiazoles, oxazolidones, triazoles and tetrazoles [68]. The tetrazole group... 

One step synthesis of dissymetricai amines R2NR from nitriles in the presence of copper catalysts... 

N-Pentylamine Synthesis N-Pentylamine s structure (CH3CH2CH2CH2CH2NH2) indicates it is composed of 5 carbon atoms. Since the starting material cannot have over 4 carbon atoms, the synthesis of the amine must include an increase in the carbon skeleton of the starting material. Synthesis via reduction of nitriles (-CHN) has the special feature of increasing the length of a carbon chain, producing a primary amine that has one more carbon atom than the alkyl halide from which the nitrile was made. 

Synthesis of Amidines from Amines and Nitriles. An efficient one-step preparation of Af,Af -disubstituted amidines is possible by direct nucleophilic addition of an amine to a nitrile using catalytic amounts of samarium iodide (eq Alternatively, an... 

The use of supported copper has been explored in a number of reactions with good conunercial potential. Some examples are oxidative dehydrogenation (already mentioned), dehydrogenation of esters (Evans et al., 1974 Agarwal et al., 1987 Chen et al., 1989), hydrolysis of nitriles (Lee et al., 1988), amination of esters (Barrault et al., 1991), and one-step synthesis of dissymmetric amines [R2NCH3 or RN(CH3)2] from the corresponding nitriles, methanol, and hydrogen (Barrault et al., 1993). 

Intramolecular nucleophilic attack onto the carbon centres of nitriles constitutes a common strategy employed in the synthesis of heterocyclic amines. However, a recent preparation of 5 -amino-m-terphenyls from arylidene and 1-arylethylidene-malononitriles has demonstrated that such reactions can be applied to the synthesis of carbocyclic amines (Scheme 3). 

First of all, two examples of the change in selectivity of catalytic reactions performed in "silent" or ultrasound conditions should be recalled (for a discussion, see Ch. 4, p. 145). The classical paper by Ando 2 refers to the reaction between benzyl bromide and potassium cyanide on alumina in toluene. In the sonochemical reaction, the main product is benzyl cyanide, while in a silent condition it is the Friedel-Craft adduct. When the Strecker synthesis of a-amino nitriles from an aldehyde, potassium cyanide, and an amine in acetonitrile is performed with alumina and ultrasound, the main product (selectivity = 90%) is the a-amino nitrile. In the same conditions, except for the absence of ultrasoimd, the selectivity for the same product is only 64%. If ultrasound is used without alumina, the selectivity is 23%, and 6% if only stirring is used. 

For other example, see J. Wang, Y. Masni, M. Onaka, Eur. J. Org. Chem. 2010, 1763-1771. Synthesis of a-amino nitriles from carbonyl componnds, amines, and trimethylsUyl cyanide comparison between catalyst-free conditions and the presence of tin ion-exchanged montmoriUonite. 

Table 4 Synthesis of primary amines from nitriles via aluminum imines...

Nitroarenes and nitriles could also be employed as amine precursors. In 2010, Li and co-workers reported a ruthenium complex-catalyzed synthesis of tertiary amines by A -alkylation of nitroarenes with alcohols (Eq. 14) [87], In this method, large excess amounts of the alcohols (mostly 7.5 equiv.) are necessary to reduce the nitroarenes to anilines prior to A -alkylation. In 2011, Shi and co-workers also developed an amination reaction for secondary amine synthesis from nitro or nitrile compounds (Eq. 15) [88]. In the same year, Deng and co-workers reported a ruthenium-catalyzed method for tertiary-amine synthesis from nitriles and primary alcohols [89]. In 2013, Beller and co-workers reported another A -alkylation reaction of nitrile compounds with secondary alcohols [90]. 

This chapter describes newly discovered reactions and synthetic utilities of lithium aminoborohydrides (LABs) including (1) the reduction of nitriles to amines, (2) the direct synthesis of amine-borane complexes from LABs and benzylic or alkyl halides (nitrogen transfer), and (3) the tandem nitrogen transfer/reduction of halogen-substituted benzonit-riles to give the corresponding aminobenzylamines. 

Further examples of the synthesis of primary amines from oximes, azides, nitriles,isocyanides,aldehydes, and Grignard reagents have also been reported. 

---