Alkyl cyanide, from amines

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... 

When an alkyl halide is treated with silver cyanide, reaction takes place in the usual way a silver halide and an organic compound are formed. The product, however, is not an alkyl cyanide, as is the case when potassium cyanide is used, but an isomeric compound. The substances prepared from silver cyanide are called isocyanides, isonitriles, or carbylamines. The last name is given to them on account of the fact that they unite with acids and thus resemble the amines. The addition-products do not, however, resemble salts in their chemical properties. When hydrogen chloride is passed into an ethereal solution of methyl isocyanide, a compound of the formula 2CH3NC.3HCI is formed, which is decomposed when brought into contact with water. 

Tertiary amines are also known to effect the phase transfer addition of cyanide ion to primary, allylic, and benzylic halides [9]. The reported effect of amine structure on catalytic efficiency closely parallels that reported by Hennis for ester formation in a two-phase system (see Sect. 1.7). Both the nitrogen of the amine and the carbon bearing halide of the alkyl bromide must be sterically accessible for the reaction to succeed. Thus, -hexylamine is effective in concert with -butyl bromide but the combinations of either 5-butyl bromide and -hexylamine or -butyl bromide and cyclohexylamine are not. Tertiary amines are generally more effective than secondary or primary amines. In addition, the yields of primary nitriles decrease dramatically with the size of the primary alkyl bromide from quantitative with n-butyl to only 6% with -decyl bromide when -hexylamine is used as phase transfer catalyst. On the other hand, tributylamine was equally useful as a catalyst for the quantitative conversion of either 1-bromohexane or 1-bromodecane to the corresponding nitriles [9]. In general, these observations accord with those of Hennis and coworkers indicating that this reaction is an example of in situ formation of and catalysis by quaternary ammonium salts [10]. 

Because nitriles can be prepared from alkyl halides by nucleophilic substitution with cyanide ion the overall process RX RC=N RCH2NH2 leads to primary amines that have one more carbon atom than the starting alkyl halide... 

Heterocyclic structures analogous to the intermediate complex result from azinium derivatives and amines, hydroxide or alkoxides, or Grignard reagents from quinazoline and orgahometallics, cyanide, bisulfite, etc. from various heterocycles with amide ion, metal hydrides,or lithium alkyls from A-acylazinium compounds and cyanide ion (Reissert compounds) many other examples are known. Factors favorable to nucleophilic addition rather than substitution reactions have been discussed by Albert, who has studied examples of easy covalent hydration of heterocycles. 

In asymmetric Strecker synthesis ( + )-(45,55 )-5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has been introduced as an alternative chiral auxiliary47. The compound is readily accessible from (lS,25)-2-amino-l-phcnyl-l,3-propancdioI, an intermediate in the industrial production of chloramphenicol, by acctalization with acetone. This chiral amine reacts smoothly with methyl ketones of the arylalkyl47 or alkyl series48 and sodium cyanide, after addition of acetic acid, to afford a-methyl-a-amino nitriles in high yield and in diastereomerically pure form. 

The cyanides 246, obtained from aldehydes R CHO (R1 = alkyl, Ph or PhCH=CH), amines HNR2R3 (aniline or morpholine etc.) and potassium cyanide undergo autoxidation in the presence of potassium r-butoxide to give amides (equation 89)259. 

Di-2-pyridyl sulphite (343) (from 2-pyridone and thionyl chloride in the presence of triethylamine) transforms primary aliphatic and aromatic amines RNH2 into N-sulphinylamines RN=S=0 and it dehydrates amides ArCONH2 to aryl cyanides, aldehyde oximes RCH=NOH (R = Cxlf 7. 4-MeOCgH4 or PhCH=CH) to the cyanides RCN and A-alkyl- and TV-ary Iformamides RNHCHO to isocyanides RNC. Aliphatic and aromatic... 

Formation and Reduction of Nitriles Like the azide ion, cyanide ion (- C=N ) is a good Sn2 nucleophile it displaces leaving groups from unhindered primary and secondary alkyl halides and tosylates. The product is a nitrile (R—C=N), which has no tendency to react further. Nitriles are reduced to primary amines by lithium aluminum hydride or by catalytic hydrogenation. 

IR-spectra of pseudostrychnine in the solid phase and in solution indicate that it exists almost entirely in the carbinolamine form CXCVI. Two other forms might be expected to exist in equilibrium with CXCVI in solution the immonium form CXCVII, produced by proton-catalyzed loss of the hydroxyl group, is totally excluded on steric grounds the keto-amine form CXVIII, on the other hand, almost certainly exists in equilibrium with CXCVI in solution, but in concentrations which escape detection by physical methods. Its presence is deduced from some of the chemical reactions of pseudostrychnine. The easy formation of O-alkyl ethers (125) by interaction with methanol or ethanol even at room temperature almost certainly involves nucleophilic attack of the alcohol molecule on the carbonyl carbon in CXCVIII or in the O-protonated form CXCIX (R = H) to yield a hemiacetal as a first step likewise, the formation of 16-cyanostrychnine (XXV CN instead of OH) must involve addition of cyanide ion to CXCVIII, and the reaction with... 

The amino acid synthesis from Strecker has been known since 1850 [25]. Stereoselective versions of this synthesis start with chiral amines, which are condensed with carbonyl compounds to form imines. Addition of hydrogen cyanide and subsequent hydrolysis of the amino nitriles yields the amino acids. When ketones are used for the condensation, a-alkylated amino acids are obtained in high yields and optical purities... 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

Certain nitriles add amines to form N-substituted amidines. This reaction has been modified and extended through the use of ammonia and alkyl- or aryl-ammonium salts of sulfonic acids. Many amidines have been prepared in yields ranging from 13% to 86%. Some amidines are obtained in better yields by heating a cyanide with ammonium thiocyanate or an alkylammonium thiocyanate."... 

When hydrolized they yield alkyl amines in which the alkyl radical is linked to nitrogen and they may be made, as previously stated (p. 72), from the iso-cyanides through the dichloride by means of silver oxide. 

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