Ammonolysis: of alcohols

A similar ammonolysis of alcohols in the presence of certain metallic oxide catalysts is, however, extensively used on the large scale for the manufacture of all... 

It will be recalled that, in the ammonolysis of alcohols, the substitution of a nickel catalyst for alumina results in the appreciable formation of nitriles. Similarly, by an appropriate choice of catalysts, nitriles can be obtained by the ammonolysis of aldehydes ... 

The vapor-phase ammonolysis of alcohol is much more complicated, because of side reactions. Although much information is available concerning operating conditions, effect of flow rates, and the effects of catalysts, there is little to be found in the literature on actual mechanism. 

In general, the reactions of the perfluoro acids are similar to those of the hydrocarbon acids. Salts are formed with the ease expected of strong acids. The metal salts are all water soluble and much more soluble in organic solvents than the salts of the corresponding hydrocarbon acids. Esterification takes place readily with primary and secondary alcohols. Acid anhydrides can be prepared by distillation of the acids from phosphoms pentoxide. The amides are readily prepared by the ammonolysis of the acid haUdes, anhydrides, or esters and can be dehydrated to the corresponding nitriles (31). 

Amination. Amyl alcohols can react with ammonia or alkylamines to form primary, secondary, or tertiary-substituted amines. Eor example, 3-methyl-butylamine [107-85-7] is produced by reductive ammonolysis of 3-methyl-1-butanol over a Ni catalyst at 150°C (59). Some diisoamyl- and triisoamyl amines are also formed in this reaction. Good selectivities (88%) of neopentyl amine [5813-64-9] are similarly produced by reductive ammonolysis of neopentyl alcohol (60). 

Ammonium acetate and sodium methoxide are effective catalysts for the ammonolysis of soybean oil (49). Polyfunctional amines and amino alcohols such as ethylenediamine, ethanolamine, and diethanolamine react to give useful intermediates. Ethylenediamine can form either a monoamide or a diamide depending on the mole ratio of reactants. With an equimolar ratio of reactants and a temperature of >250° C, a cyclization reaction occurs to give imidazolines with ethylenediamine (48) ... 

Mandelamide has been prepared by treating the ethyl ester with concentrated aqueous ammonia,12 and a saturated alcoholic solution of ammonia has been used to effect ammonolysis of the methyl ester.1 3 Esters of mandelic acid were treated with liquid... 

These studies showed the particular resistance of the benzoyl group attached to a primary hydroxyl group. The only exception62 is the ammonolysis of 2,3,4,5-tetra-O-benzoyl-L-arabinononitrile, which, in isopropyl alcohol containing 5.5% of ammonia, affords l,l-bis(benza-mido)-l-deoxy-L-erythritol (the L enantiomer of 10 see p. 83) and not its 4-O-benzoylated derivative. 

The Hines64 showed that, as acids, ethanol, isopropyl alcohol, and tert-butyl alcohol are weaker than water, whereas methanol is stronger. The influence of the solvent could thus be interpreted in terms of equation 1. In methanol, the equilibrium would be more displaced to the right, and the rate of simple ammonolysis and transesterification would be enhanced, with concomitant decrease in the yields of amido sugars. In water (for the ammonolysis of sugar acetates) and in alcohols other than methanol, the equilibrium would be displaced to the left and this would allow operation of the orthoester mechanism a better chance. The isolation, from the reaction in isopropyl alcohol, of mono-O-benzoylated bis(benzamido)alditols, could also be explained on this basis. 

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. 

Saponification is the base-mediated hydrolysis of an ester, yielding its component carboxylate salt and alcohol. Ammonolysis of esters gives amides. Esters react with Grignard reagents to give tertiary alcohols. With lithium aluminum hydride, on the other hand, they are reduced to primary alcohols. 

Three inosamines were obtained in the course of efforts to synthesize myo-inositol by the nitro-sugar cyclization (see p. 142). However, the methods which have been the most productive of new inosamines are those which are well known as means of preparing amino sugars and aminopolyhydric alcohols, namely, reduction of imine derivatives of carbonyl compounds (in this case, inososes) and ammonolysis of halohydrins and epoxides. 

Of commercial interest is the direct reaction of alcohols with ammonia at elevated pressures and temperatures in the presence of a dehydrating catalyst such as alumina gel. This process is known as ammonolysis and gives a mixture of primary, secondary and tertiary amines (Reaction XXVII). 

Preparation of diazoketones and their rearrangements during hydrolysis (method 271) and alcoholysis (method 295) are discussed elsewhere. Ammonolysis of diazoketones leads to amides of acids containing one more carbon atom than the original acyl halide. Halogen atoms may be present in a remote position on an aliphatic chain. The reaction is carried out by heating the diazoketone in alcohol or dioxane solution with aqueous ammonia in the presence of silver oxide or silver nitrate catalysts. Substituted acetanilides are formed when aniline is used in place of ammonia. ... 

C) Ammonolysis of Alkyl Halides. Place 20 ml of a saturated alcoholic solution of ammonia in methanol (90 per cent) in each of two test tubes. To the first add 2 g of n-amyl bromide, and to the second 2 g of amyl bromide. Cork, shake, label, and set aside until the following laboratory period. Add to each reaction mixture 20 ml of water, and separate the upper layer of amine (and imchanged halide). Test two drops of each product for amy-lene by shaking with 2 ml of 0.1% potassium permanganate or bromine water. Record the observations. Place the sample of amine in the proper bottle provided by the instructor for future study. 

The ammonolysis of the alkyl monohalides suffers from the difficulties involved in the separation of the mixture of amines. The reaction is best carried out by adding the halide to a saturated (15-20%) alcoholic solution of ammonia. If a greater proportion of primary amine is desired, 9-10 moles of ammonia and one mole of halide are allowed to stand at room temperature for several days, or ammonium nitrate is added and the amomit of ammonia is reduced. The addition of salt reduces the solubility of the halide... 

I) Ammonolysis of Esters. (1) To 5 ml of saturated solution of ammonia in methanol add 2 ml of ethyl acetate. Cork, and allow to stand until the next laboratory period. Place the contents of the tube in an evaporating dish and evaporate the alcohol over a water bath. Determine the weight of the amide. 

Properties White crystals. Mp 119C, bp (decomposes). Soluble in water and alcohol. Combustible. Derivation Ammonolysis of cyanoacetic ester or dehydration of ammonium cyanoacetate. 

Fatty amines can be synthesized by reacting alkylhalides with either ammonia or lower amines, from fatty acids and their derivatives (i.e., amides and ammonium salts), or by ammonolysis of fatty alcohols. Amines dissociate and reveal surface activity primarily under acidic conditions. Higher homologs, such as octadecylamine, are insoluble in water, but soluble in oil. 

There are, however, occasional uses for stannous chloride reductions on account of the mildness of the reaction. It can be employed in the reduction of 4,4 -dinitrodiphenylamine, which accompanies p-nitroaniline as an impurity when the latter is prepared by the ammonolysis of p-nitrochloro-benzene. Stannous chloride is also employed when it is desired to reduce one nitro group of two originally present. In alcoholic solution, this reduction proceeds very smoothly, yielding excellent products. 

Studies of the kinetics of the reaction have been concerned principally with the liquid-phase ammonolysis of esters and aromatic chloro compounds, presumably because the reactions are more cleancut and there is less tendency to form by-products. For example, in the ammonolysis of esters, the amide is essentially the only product, whereas with the reaction of aliphatic alcohols and ammonia an equilibrium mixture of mono-, di-, and trialkylainines is obtained. 

The ammonolysis of unsaturated carbonyl compounds in the presence of hydrogen is the most exothermic type. Reaction of phenols, alcohols, and halides with ammonia is only slightly exothermic. Aminolysis of alcohols is much more exothermic than the ammonolysis. Reactions of hydrocarbons with ammonia to form nitriles seem to be special cases in that they are extremely endothermic in nature. 

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