Ammonolysis of halides

Ammonolysis of halides is usually limited to the aliphatic series, because of the generally low reactivity of aryl halides toward nucleophilic substitution. (However, see Chap. 25.) Ammonolysis has the disadvantage of yielding a mixture of different classes of amines. It is important to us as one of the most general methods of introducing the amino ( NH2) group into molecules of all kinds it can be used, for example, to convert bromoacids into amino acids. The exactly analogous reaction of halides with amines permits the preparation of every class of amine (as well as quaternary ammonium salts, R4N X ). 

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. 

Ammonolysis of halides belongs to the class of reactions that we have called nucleophilic substitution. The organic halide is attacked by the nucleophilic ammonia molecule in the same way that it is attacked by hydroxide ion, alkoxide ion, cyanide ion, acetylide ion, and water ... 

So far we have been chiefly concerned with the synthesis of primary amines. Secondary and tertiary amines are prepared by adaptations of one of the processes already described ammonolysis of halides or reductive amination. For example ... 

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. 

In one of the ammonolysis products, halide ion exchange occurred 2FCIP(S)-N=PF2NH2... 

Delepine reaction org chem Slow ammonolysis of alkyl halides in acid to primary amines in the presence of hexamethylenetetramine. del-3,pTn re,ak-sh3n deliquescence phys chem The absorption of atmospheric water vapor by a crystalline solid until the crystal eventually dissolves into a saturated solution. del-3 kwes-3ns ... 

On reaction of ammonia with vanadium(III) halides there is ammonolysis of one V—X bond. The amidohalides VX2(NH2)-nNH3 (X = Cl62,183 or Br,183,184 n = 4-5) have an ammonia content that depends on the temperature. A similar compound V(NCS)2(NH2)-4NH3 has been prepared from V(NCS)3 in THF with NH3.185 These amidohalides are polymeric.6,185... 

Lewis acids, such as the halide salts of the alkaline-earth metals, Cu(I), Cu(II), zinc, Fe(III), aluminum, etc, are effective catalysts for this reaction (63). The ammonolysis of polyamides obtained from post-consumer waste has been used to cleave the polymer chain as the first step in a recycle process in which mixtures of nylon-6,6 and nylon-6 can be reconverted to diamine (64). The advantage of this approach lies in the fact that both the adipamide [628-94-4] and 6-aminohexanoamide can be converted to hexamethylenediamine via their respective nitriles in a conventional two-step process in the presence of the diamine formed in the original ammonolysis reaction, thus avoiding a difficult and cosdy separation process. In addition, the mixture of nylon-6,6 and nylon-6 appears to react faster than does either polyamide alone. 

Ammonolysis of aryl halides has been performed under PTC conditions.125 The reaction of 2,4-dinitro-chlorobenzene with NH3 (g) in toluene at ambient temperature and pressure gave, in the presence of 10% TBAB and after 3 h, 2,4-dinitroaniline in 16% yield (0.6% in the absence of TBAB). The reaction was complete after 24 h but the product final yield was not reported.125... 

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. ... 

Partial ammonolysis of phosphorus(V) chloride or bromide and of monoalkyl- or -aryl-substituted dichloro- or dibromophos-phines in the presence of chlorine or bromine is a general method for the synthesis, respectively, of the corresponding simple or substituted phosphonitrile halides. " This type of reaction may yield either cyclic or linear poljuners, depending upon the temperature, solvent, reaction time, and/or reagent ratio. 

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. 

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... 

If secondary and tertiary amines are desired, only 2 to 3 moles of ammonia are used. Aqueous ammonia does not react to any extent at room temperature, owing to the immiscibility of halide and water. Industrially, aqueous ammonia is used and heated in an autoclave under pressure. Tertiary halides, as, for example, tert-butyl and tert- m.y bromides, do not yield amines, but yield olefines almost exclusively. The object of the present experiment is to illustrate the ammonolysis of alkyl halides. The ammonolysis of aryl halides cannot be easily accomplished in the laboratory, as it involves the use of high pressure, and temperatures of about 200°. Industrially the method is practical. 

Introduction. The general methods for the preparation of amides are (1) ammonolysis of esters, acyl halides, and anhydrides (2) the dehydration of the ammonium salts of carboxylic acids ... 

Sulfur diimide should be obtained most simply by ammonolysis of a halide of tetravalent sulfur. Sulfur tetrachloride or trithiazylchloride (XLIV) are available as acid halides for such a reaction. The former is very readily decomposed by ammonia, but S(NH)2 cannot be identified among the reaction products which consist chiefly of S4N4, NH4C1, and chlorine (43). Only an organic derivative of (XLII) could be prepared in a solvolytic reaction of this sort with SC14, in which butylamine gave the n-butylimide (XLIII) (53). 

Sulfuryl amide (LXXIX), the diamide of sulfuric acid, has been known for a very long time. It was discovered by Traube (111, 112) and isolated as a colorless solid mp, 92-93°. It is formed in a quite normal way both in the ammonolysis of sulfuryl halides (see, for example, refs. 22,26,29, 77,103, 119) and also in the ammonolysis of sulfur trioxide (6). It is common to both modes of preparation that other reactions occur besides the formation... 

When a catalyst is essential, copper, its oxides, and salts are preferred, and these are almost always used in the ammonolysis of compounds wherein the halogen is attached to an aromatic nucleus not containing negative substituents (e.g., chlorobenzene, chlorobiphenyl (chloroxenene), and chloronaphthalene). In the treatment of alkylene, nitrophenyl, and anthraquinone halides, copper catalysts are not essential but may be used to accelerate the reaction. In the typical reactions of Class 1, presented... 

There is a dearth of information regarding the efficacy of emulsifying and wetting agents in the amination process. Such agents appear to have important potential utility in the ammonolysis of aryl halides such as... 

The ammonolysis of aromatic halides follows a pattern similar to the esters. For example, substituted chloronitrobenzenes containing a la-bilized chlorine atom react in aqueous ammonia at a rate proportional to the concentration of both reactants—indicating that the mechanism is second order. ... 

Ammonolysis of aromatic halides, however, may lead to unexpected products. For example, Gilman and Martin report that aryl ethers, thio ethers, and sulfones with ortho-halogen substituents rearrange to metarsubstituted anilines when treated with sodamide in liquid NH3. 

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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