Alkyl, amines cyanides

Relation to Amines.— When the alkyl cyanides are treated with nascent hydrogen an alkyl amine is formed in which the alkyl radical has one carbon more than the alkyl radical of the cyanide. 

Iso-nitriles, Carbylamines.— The alkyl cyanides because of tlieir relations to acids are known as acid nitriles methyl cyanide by hydrolysis yields acetic acid and it is thus known also as acetic nitrile. The iso-cyanides being isomeric with the nitriles are also termed isonitriles. Another name is sometimes used because of. their amine relationship, viz., carbyl-amine methyl iso-cyanide, CH3—NC, being methyl carbylamine. The lower alkyl-iso-cyanides are liquids with a very strong disagreeable odor. They are readily hydrolized by water but form salts with hydrochloric acid and also with silver cyanide. 

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. 

Most tertiary butylamine (and other tertiary alkyl amines) is produced using hydrogen cyanide in the Ritter reaction. Isobutylene [97] or methanol [98] is reacted with hydrogen cyanide under acidic conditions to generate r-butylamine ( 1.46/lb) ... 

The Ritter reaction proceeds by a nucleophilic addition of hydrogen cyanide followed by the hydrolysis of the intermediate formamide. Higher tertiary alkyl amines are produced using the same method with higher alkenes and alcohol. This is considered the most practical way to produce tertiary amines [99]. 

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... 

Ritter Reaction (Method 4). A small but important class of amines are manufactured by the Ritter reaction. These are the amines in which the nitrogen atom is adjacent to a tertiary alkyl group. In the Ritter reaction a substituted olefin such as isobutylene reacts with hydrogen cyanide under acidic conditions (12). The resulting formamide is then hydroly2ed to the parent primary amine. Typically sulfuric acid is used in this transformation of an olefin to an amine. Stoichiometric quantities of sulfate salts are produced along with the desired amine. 

Although in the dry state carbon tetrachloride may be stored indefinitely in contact with some metal surfaces, its decomposition upon contact with water or on heating in air makes it desirable, if not always necessary, to add a smaH quantity of stabHizer to the commercial product. A number of compounds have been claimed to be effective stabHizers for carbon tetrachloride, eg, alkyl cyanamides such as diethyl cyanamide (39), 0.34—1% diphenylamine (40), ethyl acetate to protect copper (41), up to 1% ethyl cyanide (42), fatty acid derivatives to protect aluminum (43), hexamethylenetetramine (44), resins and amines (45), thiocarbamide (46), and a ureide, ie, guanidine (47). 

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. 

Aminonitrile formation on 125 with potassium cyanide and piperidine hydrochloride affords the derivative, 135. Hydrolysis as above gives the corresponding amide (136). Debenzylation is accomplished by catalytic reduction. Alkylation of the secondary amine with the side chain (96) used in the preparation of diphenoxylate affords pirintramide (138) This compound, interest-... 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

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. 

ISONITRILES. This designation includes isocyanides (see Vol 3, C582-L to C583-L and Vol 7, I135-R for Cyanicic Acid and-Derivatives) and Carbylamines, R.NiC. The first isonitriles were prepd in 1886 by Gautier, by the action of Ag cyanide on alkyl iodides. Later, Hofmann prepd them by the action of chlf ale KOH on primary amines ... 

The reaction of diazo compounds with amines is similar to 10-15. The acidity of amines is not great enough for the reaction to proceed without a catalyst, but BF3, which converts the amine to the F3B-NHR2 complex, enables the reaction to take place. Cuprous cyanide can also be used as a catalyst. The most common substrate is diazomethane, in which case this is a method for the methylation of amines. Ammonia has been used as the amine but, as in the case of 10-44, mixtures of primary, secondary, and tertiary amines are obtained. Primary aliphatic amines give mixtures of secondary and tertiary amines. Secondary amines give successful alkylation. Primary aromatic amines also give the reaction, but diaryl or arylalkyl-amines react very poorly. 

The first recorded correlation of dipole moments with substituent constants was observed by Taft (3), who reported results for alkyl cyanides, chlorides, iodides, and tertiary amines. Kross and Fassel (31) have reported the correlations of dipole moments for 4-substituted nitrobenzenes with the simple Hammett equation. Rao, Wohl, and Williams (32) have studied the correlation of dipole moments of disubstituted benzenes with eq. (1) and of monosubstituted benzenes with the equation... 

As esters the alkyl halides are hydrolysed by alkalis to alcohols and salts of halogen acids. They are converted by nascent hydrogen into hydrocarbons, by ammonia into amines, by alkoxides into ethers, by alkali hydrogen sulphides into mercaptans, by potassium cyanide into nitriles, and by sodium acetate into acetic esters. (Formulate these reactions.) The alkyl halides are practically insoluble in water but are, on the other hand, miscible with organic solvents. As a consequence of the great affinity of iodine for silver, the alkyl iodides are almost instantaneously decomposed by aqueous-alcoholic silver nitrate solution, and so yield silver iodide and alcohol. The important method of Ziesel for the quantitative determination of alkyl groups combined in the form of ethers, depends on this property (cf. p. 80). 

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... 

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