Ammonolysis, in liquid ammonia

Ammonolysis is the direct reaction of ammonia with an organic compd. This reaction is used for the prepn of various amines, ni-tramines, etc and some of these products are or may be converted into expls Refs l)W.C.Fernelius G. B. Bowman,Che m-Revs 26, 3—48(1940)(286 refs)(Ammonolysis in liquid ammonia) 2)Kirk Othmer 1 (1947), 826-44(89 refs) 3)A.C.Stevenson, IEC Sept 1948 to 1952, under Unit Process Review 4)G.H.Coleman,IEC Sept 1953,... 

C The decapeptide 2 was reacted with a 3-4 fold excess of the bromo-isocaproyltriglycine chloride described above to yield the fourteen-membered a-bromo acyl compound. After a 4-5 day ammonolysis in liquid ammonia the corresponding tetradecapeptide (3) was acylated by the d-bromoisocaproyltriglycine chloride once again with difficulty and the 18-membered product converted by treatment with liquid ammonia to the famous octadecapeptide with a molecular weight of 1213. 

Tetrahedral Anions. The hydrolysis of the [BHJ anion in aqueous DMSO has the kinetic form for a general-acid-catalysed reaction, but with the catalytic coefficients and k-s.+ very different to the values observed for aqueous media. This difference is ascribed to the inability of DMSO to act as a proton relay system. A series of molecular orbital calculations suggest that BH5 could be a metastable intermediate in the hydrolysis of [BH They indicate the presence of identifiable BH3 and Hg subunits in the structure. The authors conclude, however, that limitations in the theoretical methods used do not yet allow experimental and computational results to be reconciled (at least to within a few kcal). The acid-cat ysed ammonolysis in liquid ammonia is first-order in both [NHJ+ and [BHJ, but is appreciably slower than the corresponding reaction in water the rate is markedly decreased by increases in ionic strength. This may be due to the participation of a water molecule in the latter case. The rates of reduction of a variety of substrates by [BHJ have been reported, and for the reduction of ketones it is suggested on the basis of H/T isotope effects that a four-centre transition state is involved. 

Inorganic amides contain the ion NH2". They are formed by the action of ammonia on metals or by the ammonolysis of nitrides. The heavy metal amides are prepared by meta-thetical reactions in liquid ammonia, e.g. 

Initial C-perfluoroalkylation of p diketonesoccurs dunng thenUV irradiation in the presence of perfluoroalkyl iodides in liquid ammonia Pluorinated enami-noketones are obtained by subsequent ammonolysis of a difluoromethylene group and removal of the acetyl group [131] C-alkylation of dimethyl malonate takes... 

An X-ray crystal structure of the Pr N-derivative shows the presence of a bent, 2-coordinate P atom, equal P- N distances, and accurately planar 3-coordinaie N atoms as in (c) above.In liquid ammonia ammonolysis also occurs ... 

The versatility of cyanide and bipyridyl ligands has been used to stabilize low oxidation states. By using potassium in liquid ammonia, K3Ti (CN)6 is reduced to K2Ti (CN)4 and TiBt3 - - KCN to K4Ti°(CN)4. With ZrBt3 and M CN (M = K, Rb) in liquid ammonia, ammonolysis occurs and zerovalent Zr is produced ... 

Ammonolysis of 2-chlorobenzothiazole in liquid ammonia was studied by Lemons et al. and found to be approximately first-order with respect to this substrate at the fairly high concentrations used. The actual nucleophilic reagent was, as expected, the neutral species NH3, and reaction via the amide ion NH2 arising from the autoprotolysis equilibrium [Eq. (5)] was excluded on the grounds that addition of ammonium chloride did not depress the reaction rate. In accordance with this interpretation and in connection with the existence of aromatic substitutions other than normal it is of interest that 2-chlorobenzothiazole was found to react difiFerently with sodamide, although the products were unidentified in this case. 

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... 

Thus, a stable derivative of phosphorus triamide, P(NH2)3, could not be obtained. Such expectations were encouraged by recent work of Kodama and Parry (12), who succeeded in ammonolyzing phosphorus trifluoride-borane, F3P.BH3, with formation of a stable phosphorus triamide-borane, (H2N)3P.BH3. Ammonolysis of boron- or phosphorus-fluorine rather than -chlorine bonds is advantageous, since ammonium fluoride is insoluble in liquid ammonia and can easily be separated, while ammonium chloride is readily soluble. 

The acid and base analogs of ammonia as a solvent is specified by this equilibrium as NH41 and NH inns. All substances which undergo ammonolysis and hence bring about an increase in the ammonium ion concentration yield acitl solutions Thus P S, dissolves in liquid ammonia to give an acid solution as follows. 

Ionization of liquid ammonia and water solutions.—Solutions of certain salts in liquid ammonia are good conductors of electricity so that liquid ammonia approaches water in its ionizing power. The effect, however, is largely due to the high speed at which the ions are supposed to travel in the solvent. For example, E. C. Franklin and H. P. Cady1 find that univalent ions travel, at —33°, nearly three lames as fast as in aq. soln. at 18°. Just as the solvent water, in the ionization theory of hydrolysis, is supposed to be ionized H20=0H -f-H, so in ammonolysis, the solvent ammonia is supposed to be ionized NH3==NH2-j-H . Sodamide, NaNH, furnishes sodium ions Na and amide ions NH 2 when dissolved in liquid ammonia, and it is to be considered as a base. It reddens phenolphthalein. The neutralization of this solution results in the union of H ions with NH2 ions to form ammonia molecules, just as the neutralization of bases is regarded as an effect of the union of H and OH ions. Acetamide, CH3.CO.NH2, ionizes in liquid ammonia in an analogous manner CH3.CO.NH2 CH3.CO.NH -f-H, and it thus behaves as an acid. 

The series of investigations carried out at the L. Ya. Karpov Physicochemical Institute by A. I. Shatenshtein, V. A. Pleskov, A. M. Monoszon, and others has been concerned with the properties of acid-base equilibria in liquid ammonia. Measurements have been made of the kinetics of ammonolysis catalysed by acids (Shatenshtein... 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

Aminopyrazines are conveniently prepared from carboxamido-pyrazines by application of the Hofmann reaction (see Section V,B). Thus, Camerino and Palamidessi prepared aminopyrazine in 80% yield from carboxamidopyrazine.312 Aminopyrazine may also be prepared from the reaction of pyrazine with sodamide in liquid ammonia,313 and 3-amino-2,5-dimethylpyrazine is the product of amination of 2,5-dimethylpyrazine with sodamide in dimethyl-aniline.311 The ammonolysis of halopyrazines also represents a useful preparative procedure for aminopyrazines (see Section V,C). This reaction proceeds most easily in the case of fluoro compounds for example, fluoropyrazine is converted into aminopyrazine in 70% yield by treatment with concentrated aqueous ammonia at room temperature for 3 days,299 whereas the corresponding reaction with chloropyrazine has been carried out in a sealed tube at 150°.147 Alkaline hydrolysis of 2,4-dihydroxypteridines followed by decarboxylation yields aminopyrazines 315 thus, high-temperature alkaline hydrolysis of 7-methyl-2,4-dihydroxypteridine (7-methyIlumazine) gives, after decarboxylation of the intermediate pyrazinecarboxylic... 

After the reaction, the solid sodium salt is filtered off and methanol is distilled off under reduced pressure. Hydroxylamine can also be prepared by the ammonolysis of hydroxylammonium salts in liquid ammonia. The ammonium salt precipitates and is filtered off Hydroxylamine is obtained after evaporating the excess ammonia. 

Correspondingly, metal amides in liquid ammonia have a basic character. The reaction of ammonium salt with metal amide in liquid ammonia is analogous to the neutralization of acid and base in water. The heats of neutralization in ammonia are even larger than in water. The process of hydrolysis corresponds to ammonolysis in ammonia. This results in ammonobasic compounds, for example, in the infusible precipitate HgNH2Cl from HgCl2. 

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