Amine ammonium halide

The alkylation of neutral amines by halides is complicated from a synthetic point of view by the possibility of multiple alkylation that can proceed to the quaternary ammonium salt in the presence of excess alkyl halide. 

It is noteworthy that benzyltriethylammonium chloride is a slightly better catalyst than the more lipophilic Aliquat or tetra-n-butylammonium salts (Table 5.2). These observations obviously point to a mechanism in which deprotonation of the amine is not a key catalysed step. As an extension of the known ability of quaternary ammonium halides to form complex ion-pairs with halogen acids in dichloromethane [8], it has been proposed that a hydrogen-bonded ion-pair is formed between the catalyst and the amine of the type [Q+X—H-NRAr] [5]. Subsequent alkylation of this ion-pair, followed by release of the cationic alkylated species, ArRR NH4, from the ion-pair and its deprotonation at the phase boundary is compatible with all of the observed facts. 

Alternatively, oxidation of a mixed solution of cobalt(ll) halide-ammonium halide or cobalt(lI) nitrate-ammonium nitrate in the presence of excess ammonia can form the amine complexes. Such oxidation may be carried out by passing air through the solution for several hours. The yield is high in the presence of activated charcoal. 

The major previously used routes to the higher cages (i.e. where n > 4) involved elimination reactions between aluminium alkyls and primary amines or the reaction of an aluminium hydride species, e.g.. MesN AlHs orLiAlH4 with primary amines or primary ammonium halides. A number of other routes had also been used among which was the reaction between a nitrile and aluminium hydride, Equation (8.7). 

Primary amine Primary alkyl halide Ammonium halide salt Secondary amine Hydrogen halide ... 

Tertiary amines do not react with nitrous acid, acetyl chloride, benzoyl chloride, benzenesulfonyl chloride, but react with alkyl halides to form quaternary ammonium halides, which are converted by silver hydroxide to quaternary ammonium hydroxides. Quaternary ammonium hydroxides upon heating yield (1) tertiary amine pins alcohol (or, for higher members, olefin plus water). Tertiary amines may also be formed (2) by alkylation of secondary amines, e.g., by dimethyl sulfate, (3) from amino acids by living organisms, e g, decomposition of fish in the case of trimethylamine. 

In conclusion, SNAr reactions are often facihtated by polar protic solvents such as butanol or by polar solvents in the presence of Brpnsted or Lewis acids. When displacements of halides with amines are used, both polar and protic solvents can solubilize the ammonium halides resulting from the reactions, and lead to the formation of Brpnsted acids. Fluoride or chloride ions are preferred leaving groups for this reaction. Suliinyl and sulfenyl groups require somewhat harsher conditions. 

Quaternary ammonium halides are formed by reaction of alkyl halides and tertiary amines. 

Amines react with primary alkyl halides to give alkylated ammonium halides. Alkylation proceeds by the SN2 mechanism, so it is not feasible with tertiary halides because they are too hindered. Secondary halides often give poor yields, with elimination predominating over substitution. 

The dimethyl amine derivative produced was quaternized directly by methyl iodide, added slowly to a chilled solution of the ternary amine in ethyl acetate. When other ring substituents are present, the reductive eunination leads to isomeric configurations, as noted in Table I. Quaternary ammonium halide salts were characterized by melting point, TLC, or microanalytical data and and NMR. 

The reaction of ammonia with primary alkyl halides generally forms a mixture of primary, secondary, and tertiary amines and even a certain amount of the quaternary ammonium halide. Still, the method may be profitable for obtaining primary amines if the halogen compound is above C, and excess ammonia is employed, for then polyalkylation is less likely and the products, having widely different boiling points, are more readily separated. Thus w-butyl bromide and a large excess of ammonia in alcohol solution at room temperature give a 47% yield of w-butylamine. ... 

Crotti and co-workers extensively studied the ring-opening functionalization of oxi-ranes using a variety of alkali-metal salts. Several oxiranes were reacted with ammonium halides [119], KCN [120], NaNa [121], lithium acetyhde [122], amines [123], and ketone enolates [124] in the presence of alkali-metal salts to afford the formation of the corresponding 8-functionalized alcohols and some of the results are listed in Table 1. 

The reaction between ammonia and diborane depends upon the conditions. Excess of ammonia at low temperatures produces the salt-like diammoniate, [(NH3)2BH2]" BH4 , because with NH3 there is an unsymmetrical cleavage (BHa" + BH4 ) in contrast to the symmetrical one (BH3 -f BHg) resulting from reactions with amines. The monomer BH3.NH3 has indeed been made by the action of an ammonium halide on a borohydride ... 

Reactivity follows the sequence RI > RBr > RC1, and SnL > SnBr2 > SnCl2. The uncatalysed reaction of methyl iodide with stannous iodide at 160 °C has been reported,72 but usually a catalyst is necessary. These catalysts are similar to those which are used for the direct reactions, and include dialkyl sulphides, amines, ammonium and phosphonium salts, and copper(II). The trialkylstibines appear to be particularly effective and the compounds RSnX3, R = Ci to Cis, have been prepared by this method. A similar reaction with the a,co-dihalides, X(CH2) X, n = 4-5, provides access to functionally substituted tetraorganotin compounds, but the aryl halides are unreactive. 

Phase-transfer agents are the most popular catalysts for the Halex reaction with alkaline fluorides. All types of transfer agents have been claimed tetraalkyl-ammonium halides (refs. 34, 48), Aliquat 336 (ref. 49), branched pyridinium halides (eventually supported on a polymer) (refs. 50 to 53), tetraalkylphosphonium chlorides (refs. 42, 54 - 57) or bromides (ref. 12), crown-ethers (refs. 58, 59) eventually associated with Ph4PBr (refs. 43, 60), tris-(dioxa-3,6-heptyl)amine (TDA-1) (ref. 61) or polyethyleneglycols (PEG) (ref. 62). 

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