Alkylamines isolation

The first benzazetidine (243) was isolated from the photolysis of 3-phenyldihydroben-zotriazine (242) (66JA1580). Another route to benzazetidines involving formation of the N to aryl-C bond utilizes intramolecular nucleophilic substitution via aryne (287). It is not general, however, and is only satisfactory when R and/or are alkoxy groups. The reaction also fails for iV-alkylamines (78LA608). 

FIGURE 22.5 The diazonium ion generated by treatment of a primary alkylamine with nitrous acid loses nitrogen to give a carbocation. The isolated products are derived from the carbocation and include, in this example, alkenes (by loss of a proton) and an alcohol (nucleophilic capture by water). 

By contrast, alkylamination of naphthazarin (7) in the presence of sodium dithionite followed by oxidation gives l,4-bis(alkylamino)-5,8-naphthoquinone (31).18,19 However, Kikuchi and co-workers20 obtained isomeric l,5-bis(alkylamino)-4,8-naphthoquinone (32) from the reaction of leuco naphthazarin (33) with alkylamine They also isolated 5-alkylamino-leuco-naphthazarin (34) as an intermediate, which is further aminated at the 1-position to give 32. Bloom and Dudek21 have studied the structure of leuco aminonaphthoquinones and their tautomeric equilibria in solution. They concluded that the reaction of leuco naphthazarin (33) or the leuco compound (35) derived from l,5-diamino-4,8-naphthoquinone (36) with methylamine gives mixtures of l,4-bis(methylamino)-31 (R = Me) and 1,5-bis(methylamino)naphthoquinones 32 (R = Me) after oxidation of leuco aminonaphthoquinones (Scheme 10). Some of the structures of leuco aminonaphthoquinones are shown in Scheme ll.20... 

In the presence of excess monoalkylamine, carbonyl compounds in aqueous solution are in equilibrium with the corresponding imine. In most cases these imines cannot be isolated but they are reduced at a less negative potential than the carbonyl compound. Selective reduction of such equilibrium mixtures is a useful route to alkylamines from ketones in yields of 70-90%. The process fails with hindered ketones such as camphor and with bulky amines such as fert.-butyl amine. Overall the reaction has advantages of lower costs and simpler work-up compared to the use of cyanoborohydride reducing agents. In the electrochemical reaction, protonation of carbanion intermediates occurs from the more hindered side and where two isomeric products are fomied, the least hindered amine predominates [193]. 

Diazonium salt formation Primary arylamines react with nitrous acid (HNO2) to yield stable arenediazonium salts, Ar—N+=NX . Alkylamines also react with nitrous acid, but the alkanediazonium salts are so reactive that they cannot be isolated. 

Unlike primary alkylamines, primary arenamines react with nitrous acid at 0° to give diazonium ions that, in most cases, are stable enough to be isolated as crystalline BF4Q salts. Other salts can be isolated, but some of these, such as benzenediazonium chloride, in the solid state may decompose with explosive violence ... 

The three-step procedure described here illustrates a convenient, general route to di-tert-alkylamines. Extensive purification or isolation of intermediates is not required. The reactions are easily monitored. Only in the final step is the exclusion of air and moisture necessary. It should be noted that tert-butyl-tert-octylamine is considerably more hindered than 2,2,6,6-tetramethylpiperidine. tert-Butyl-tert-octylamine is inert to methyl iodide, while 2,2,6,6-tetramethylpiperidine gives a white precipitate of the pentamethylammonium iodide within minutes upon treatment with methyl iodide at room temperature. The extreme hindrance of this amine has been exploited in the selective deprotonation of carbon adds and in other reactions.10... 

Koser isolated the intermediate N-A3-iodanyl carboxyamide 62 as a moderately stable solid by the reaction of a-phenylacetamide with [methoxy(tosy-loxy)iodo]benzene in acetonitrile, and demonstrated that the hydrolytic decomposition of 62 in acetonitrile-water affords an alkylamine with one less carbon atom [105]. 

Erysophorine (13) was isolated from the water-soluble extract of the seeds of E. arborescens Roxb. (37). The molecular formula C32H38N304.CI was established by analysis. The mass spectrum of 13 gave no molecular ion but exhibited fragments consistent with a 1,6-diene Erythrina alkaloid and a carboxylated indole-3-alkylamine. Erysophorine appeared to be a combined alkaloid, and its UV spectrum was similar to that of an equimolar mixture... 

Isolation of high yields of (201) from the analogous reaction of N-(2-chloroallyl)alkylamine argues against its involvement as a substitution intermediate. The sensitivity of the acetylene to nucleophilic addition rather than its mere isolation should be considered as part of the evidence concerning its role as an essential intermediate. Since neither (199) nor (200) exchange their CH2-hydrogens with the solvent, the isolation of labelled (200) from the reaction in tritiated liquid ammonia excluded (1) as the main substitution, while (2) and (4) are excluded since the exocyclic methylene was not labelled. The incorporation of tritium at... 

N-Trialkyl-B-trihaloborazines can be prepared without difficulty from alkylammonium halide or alkylamine and trihaloborane 4> when the resulting alkylammonium tetrahaloborate or alkylamine-trihalo-borane is refluxed in chlorobenzene. Yields are nearly quantitative in most cases. This same observation holds true for N-triaryl-B-trihalo-borazines. Extensive studies using thermogravimetric methods in addition to preparative methods did not provide for the isolation or identification of any intermediates between the amine-trihaloborane and the borazine stage of the reaction 45 4fl>. 

The three-step procedure described here illustrates a convenient, general route to di-tert-alkylamines. Extensive purification or isolation of... 

A less commonly employed method of preparation is the Kirsanov reaction.3 Strictly speaking, this is the reaction of phosphorus pentachloride with benzene-sulfonamide, which can be reacted further to form benzenesulfonyliminophos-phoranes. However, the name is now used generically to cover the reactions of triphenylphosphorus dihalides and amines in the presence of a base (Scheme 5). Attack of the amine on phosphorus gives the intermediate aminophosphonium salt and HBr, elimination of another equivalent of HBr generates the IMP. If the amine is aromatic, then 2 eq. of a mild base (e.g. triethylamine) are sufficient to perform the reaction in one pot.4 However, in the case of alkylamines, it is generally necessary to isolate the phosphonium salt and treat it with sodamide to effect the deprotonation and generate the IMP.5... 

Hydroxylamines are commonly postulated as intermediates in diese oxidations, but dey are rarely isolated or detected. Two examples of reactions in which products at the hydroxylamine oxidation level can be isolated bodi involve peroxides. Oxidation of alkylamines (2 R = Bu, Me and niCH2) with arenesul-fonyl peroxides bearing an electron-wididrawing group gave die arenesulfonyloxyamines in good yields (Scheme 6). A similar reaction of primary amines wi dibenzoyl peroxide gave benzoyloxyamines. ... 

Methods for the chlorination of secondary amines, secondary amides and imides have been reviewed. Secondary alkylamines can be chlorinated by r-butyl hypochlorite at low temperature, or by sodium hypochlorite or iV-chlorosuccinimide. A(-Bromination and A(-iodination can be brought about using the appropriate halogen, but these N-halodialkylamines are unstable and are rarely isolated. A(-Flu-oroamines and Mfluoroamides are also rare. The A(-fluoroimide (CP3S02)2NF, has, however, been prepared by direct fluorination widi fluorine. It is a stable liquid which shows promise as a fluorinating agent for aromatic compounds. ... 

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