Halides, ammonolysis

Halo, and also, though with fewer examples, nitro, alkoxysulfonyl, and methoxy substituents at a- or y-positions, but not at p-positions, are easily displaced by a wide range of nucleophiles via an addition-elimination mechanism facilitated by (i) electron withdrawal by the substituent and (ii) the good leaving ability of the substituent. y-Halopyridines are more reactive than the a-isomers p-halopyridines are much less reactive, being much closer to, but still somewhat more reactive than halobenzenes. Fluorides are more reactive than the other halides. Ammonolysis can be achieved at considerably lower temperatures under 6-8 kbar pressure. ... 

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

Aral et al. (24) have devised a novel approach to ammonolysis wherein the silyl halide is modified by complexation to pyridine (py) prior to ammonolysis ... 

Good yields of 1° amines are obtained by using large excess of ammonia. The ammonolysis proceeds best by using primary alkyl halides. The tertiary alkyl halides tend to form alkenes due to the dominance of the competing elimination reaction. 

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 ... 

You have read (Unit 10, Class Xll) that the carbon - halogen bond In alkyl or benzyl haUdes can be easily cleaved by a nucleophile. Hence, an allqrl or ben l haUde on reaction with an ethanollc solution of ammonia undergoes nucleophilic substitution reaction m which the halogen atom Is replaced by an amino (-NHJ group. This process of cleavage of the C-X bond by ammonia molecule Is known as ammonolysis. The reaction Is carried out In a sealed tube at 373 K. The primary amine thus obtained behaves as a nucleophile and can further react with allqrl halide to form secondary and tertiary amines, and finally quaternary ammonium salt. 

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. 

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 ... 

Like these other nucleophilic substitution reactions, ammonolysis is limited chiefly to alkyl halides or substituted alkyl halides. As with other reactions of this kind, elimination tends to compete (Sec. 14.23) with substitution ammonia can attack... 

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. 

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. 

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 ... 

---