Amination by Ammonolysis

Groggins and W. V. Wirth I. GENERAL DISCUSSION Classification of Reactions 

Considering the behavior of ammonia, the ammonolytic reactions may involve  

Dovble decomposition, in which the NHi molecule is split into —NH and —fragments, the former becoming part of the newly formed amine, while the latter unites with the radical —Cl, —SO H, —NO, etc., that is substituted. 

Dehydration, in which water and amines result from the ammonols is of either alcohols or phenols and from the hydroammonolyas of carbonyl compounds. 

Simple addition, in which both fragments of the NH molecule enter the new compound as in the preparation of alkanolamines from alkylene oxides, aminonitriles from unsaturated nitriles, and ureas and thioureas from isocyanates and isothiocyanates. 

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A serious disadvantage to the synthesis of amines by ammonolysis is the ormation of more than one class of amine. The primary amine salt, formed by... 

Acetone is readily converted to isopropylamines in the vapor phase under conditions that apply for the lower (Cj-C ) aldehydes. The preparation of 2-aminobutane from methylethyl ketone (butanone-2) is satisfactorily carried out in the liquid phase, preferably in the presence of butanol-2 since the latter can also be converted to amine by ammonolysis. The intranuclear ketone cyclohexanone can be converted to cyclohexylamine by hydroammonolysis in the vapor phase. The preparation of 12-amino-stearamide from the corresponding keto acid is, however, best carried out in the liquid phase. The pertinent reactions are ... 

Effect of NHj Concentration. It is necessary to distinguish between the terms ammonia ratio and ammonia concentration. The first concerns the capacity factor of the system the second, the intensity factor. Aside from economic considerations, there are no disadvantages in using a large ratio of aqueous ammonia (25-50 per cent NH3 solution) with respect to the compound being treated. I ubhin reasonable limits, an increase in this ratio promotes both the yield amfpurity of primary amine by ammonolysis or... 

Aminations by ammonolysis are usually carried out most economically at elevated temperatures and pressures. Autoclaves are commonly used for both batch and continuous processing at pressures up to 700-800 psi, whereas tubes or reaction vessels having small diameters are preferred for higher pressures. A few low-pressure reactions are carried out by batches in tubs and jacketed kettles or continuously in tubes and pipelines. 

Amination by ammonolysis, G, solid catalyst, fluidized bed [-650 MJ/kmol] 440 °C, 4 s (acrylontrile, 5 data) rate doubles 30 °C for the range 400-550 °C multitube fixed catalyst bed [-650 MJ/kmol] 230 °C, 4 s (acrylonitrile, ethyl amine, 4 data) rate doubles in 25 °C for the range 150-250 °C. 

Aromatic amines can be produced by reduction of the corresponding nitro compound, the ammonolysis of an aromatic haUde or phenol, and by direct amination of the aromatic ring. At present, the catalytic reduction of nitrobenzene is the predominant process for manufacture of aniline. To a smaller extent aniline is also produced by ammonolysis of phenol. 

Amination. Isopropyl alcohol can be aminated by either ammonolysis ia the presence of dehydration catalysts or reductive ammonolysis usiag hydrogeaatioa catalysts. Either method produces two amines isopropylamine [75-31-0] and diisopropylamine [108-18-9]. Virtually no trisubstituted amine, ie, triisopropyl amine [122-20-3], is produced. The ratio of mono- to diisopropylamine produced depends on the molar ratio of isopropyl alcohol and ammonia [7664-41-7] employed. Molar ratios of ammonia and hydrogen to alcohol range from 2 1—5 1 (35,36). 

Dicyanoacetylene, 2-hiitynedinitri1e, is obtained from dimethyl acetylenedicarboxylate by ammonolysis to the diamide, which is dehydrated with phosphoms pentoxide (44). It bums in oxygen to give a flame with a temperature of 5260 K, the hottest flame temperature known (45). Alcohols and amines add readily to its acetylenic bond (46). It is a powerhil dienophile in the Diels-Alder reaction it adds to many dienes at room temperature, and at 180°C actually adds 1,4- to benzene to give the bicyclo adduct (7) [18341 -68-9] C QHgN2 (47). 

Carbamates are formed from an amine with a wide variety of reagents, the chlo-roformate being the most common amides are formed from the acid chloride. n-Alkyl carbamates are cleaved by acid-catalyzed hydrolysis A-alkylamides are cleaved by acidic or basic hydrolysis at reflux and by ammonolysis, conditions that cleave peptide bonds. 

Aluminum ethoxide, 21, 9 Aluminum isopropoxide, 21, 9 Amalgamated zinc, 20, 57 23, 86 Amide, 20, 37, 62, 66 preparation by ammonolysis, 20, 62 Amination, by reduction of a ketone in the presence of ammonia, 23, 68 of bromoacetal with use of high-pressure hydrogenation bomb, 24, 3 of a-bromoisocaproic acid, 21, 75 of a -bromo-/3-methylvaleric acid, 21, 62... 

Tris(diphenylstibino)amine (Ph2Sb)3N is formed by ammonolysis of Ph2SbCl in liquid ammonia. The Sb3N core is almost planar.1 u In addition, crystals of the analogous methyl derivatives (Me2M)3N (M = As, Sb) contain molecules with planar M3N cores.181,182... 

Problem 21.2 Synthesize leucine, (CH,),CHCH,CH(NH,)COO, by (a) Hell-Volhard-Zelinsky reaction (Section 16.3) followed by ammonolysis. (b) Gabriel synthesis, (c) phthalimidomalonic ester synthesis, (d) reductive amination of a keto acid, (e) Strecker synthesis (addition of NH, HCN to RCH=0), (/) acetylaminomalonic ester. 

The first oxidative studies on N-acylglycosylamines were conducted on a preparative scale by Niemann and Hays.65 The N-acetyl-D-glucopyranosylamine (69) obtained by acetylation of D-glucopyranos-ylamine with ketene (or by acetylation of this amine, followed by ammonolysis) was oxidized by way of the dialdehyde 70 to the acid 71, isolated as the strontium salt. Hydrolysis of 71 led to D(+)-glyceric acid (72), thus showing the pyranose structure of 69. 

Liu and Harrod ° reported on dehydrocoupling of ammonia and silanes catalyzed by dimethyltitanocene. Tertiary silanes, for example, Ph2SiMeH, were transformed into disilazanes. Yet no polysilazanes could be obtained when reacting PhSiH3 under similar conditions. Homodehydrocoupling (which proceeds with Si-Si linking compare Scheme 18.3) effectively competed with amination reactions, indicating that the products obtained by ammonolysis of PhSiHj are polyaminosilanes [SiPh(NH2)] rather than polysilazanes [SiPhH-NH] . 

Reductive amination, the catalytic or chemical reduction of aldehydes (RCHO) and ketones (R2CO) in the presence of ammonia or an amine, accomplishes much the same purpose as the reaction of halides. It too can be used to prepare any class of amine, and has certain advantages over the halide reaction. The formation of mixtures is more readily controlled in reductive amination than in ammonolysis of halides. Reductive amination of ketones yields amines containing a ec-alkyl group these amines are difficult to prepare by ammonolysis because of the tendency of jec-alkyl halides to undergo elimination rather than substitution. 

Reductive amination of ketones yields amines containing a sec-a ky group such amines are difficult to obtain by ammonolysis because of the tendency for jec-alkyl halides to undergo elimination. For example, cyclohexanone is converted into cyclohexylamine in good yield, whereas ammonolysis of bromocyclohexane yields only cyclohexene. 

We have already encountered alkylation of amines as a side reaction in the preparation of primary amines by the ammonolysis of halides (Sec. 22.10), and as a method of synthesis of secondary and tertiary amines (Sec. 22.13). Let us look at one further aspect of this reaction, the formation of quaternary ammonium salts. 

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