Conversion of primary amines

Amines are powerful nucleophiles which react under neutral or slightly basic conditions with several electron-accepting carbon reagents. The reaction of alkyl halides with amines is useful for the preparation of tertiary amines or quaternary ammonium salts. The conversion of primary amines into secondary amines is usually not feasible since the secondary amine tends towards further alkylation. 

DeCaprio AP, Olajos EJ, Weber P, et al. 1982. Covalent binding of a neurotoxic -hexane metabolite conversion of primary amines to substituted pyrrole adducts by 2,5-hexanedione. Toxicol Appl Pharmacol 65 440-450. 

Candida antarctica lipase in hexane catalyses the conversion of primary amines RNH2 (R = Bu, CgHi7, C10H21, Ci2H25 and PhCH2) into the (R)-amines 294 by ethyl (S)-2-methylbutanoate336. 

Interestingly, there is preliminary evidence that the conversion of primary amines to dialkylnitrosamines is also catalyzed by formaldehyde (S.R. Tannenbaum, unpublished results). 

Figure 4. Proposed mechanism of formaldehyde action in promoting conversion of primary amines to N-nitroso derivatives...

The last example focuses not on the functionalization of heterocycles by a transition metal mediated carbon-heteroatom bond forming reaction, but the palladium catalyzed conversion of primary amines, including amino-heterocycles, into urea derivatives. A representative example, shown in 8.38., includes the reaction of an amino-carbazole derivative with morpholine, carbon monoxide and oxygen in the presence of catalytic amounts of palladium(II) iodide. The formation of the urea moiety proceeds with great selectivity and in high yield.49 The reaction works equally well for primary aliphatic and aromatic amines. 

Conversion of primary amines to carbonyl compounds. 4-Pyridinecarboxalde-hyde is recommended for biomimetric transamination leading to carbonyl compounds. It is particularly useful for conversion of 7-amino acids into a-kcto carboxylic acids. 

Secondary amines can be prepared by conversion of primary amines into sulfonamides, followed by N-alkylation and hydrolysis. Because sulfonamides are often difficult to hydrolyze, the N-alkylation of trifluoroacetamides has been investigated. Tri-... 

JSJS.2 Conversion of Primary Amines into Nitriles... 

Bauer J, Rademann J (2003) Trimellitic anhydride linker (TAL)—highly orthogonal conversions of primary amines employed in the parallel synthesis of labeled carbohydrate derivatives. Tetrahedron Lett 44 5019-5023... 

Recently, monoethyl phthalate (79) has been described as a reagent for the mild and selective conversion of primary amines into their corresponding phthalimides. The procedure is based on the PyBOP-promoted reaction of the anoine with monoethyl phthalate (79) yielding an intermediate phthalamic ester that cyclizes to give the desired phthalimide (Scheme 40).t ... 

Mesitylglyoxal, 3>nitromesitylgIyoxal, 3,5-dinitromesityIglyoxal, and 3,5-di-/erf-bntyl-o-benzoqninone are used for the conversion of primary amines with the amino groups on secondary carbons into ketones via Schiff bases at 0-23 C in high yields (transamination) [965] (equation 19). 

Methylamine dehydrogenase (MADH) catalyses the oxidative conversion of primary amines to aldehyde and ammonia. This enzyme is found in several methylotrophic bacteria that use amines as their principal source of carbon and energy. Experiments show unusually large primary kinetic isotope effects for the rate-limiting proton transfer step in the MADH reaction. These results imply that there is a large contribution to the proton transfer reaction from quantum tunnelling. Experiments also show that there is almost no dependence of the primary kinetic isotope effect on temperature for the methylamine substrate.151... 

COBr j has also been proposed as a substitute for COCl j in the conversion of primary amines to organic isocyanates [31], thus eliminating HBr instead of HCl. 

Azide synthesis (2, 415). In the definitive paper3 describing the conversion of primary amines into azides by a diazo transfer reaction, methyllithium is preferred to methylmagnesium chloride as the base. The reaction has been extended to hydrazones. Thus, when the hydrazones of benzophenone, fluorenone, and acetophenone are treated with methylmagnesium chloride and then with tosyl azide, the corresponding diazoalkanes are obtained in about 20% yield. 

Deamination of primary amines. The conversion of primary amines into N-sulfonamides under Schotten-Baumann conditions is the basis for the classical Hinsberg test. Baumgarten et aO have found that N-sulfonamides can be converted into N,N-disulfonimides, usually in high yield, by conversion into the sodium salt (NaH) and subsequent reaction with a sulfonyl chloride in DMF as solvent ... 

At 100 °C bulk conversion of primary amines occurs quantitatively in the presence of secondary amines. Highly branched, blocked isocyanate resins are available from polyamines and polyols (Scheme 13.1). Since nontoxic components are used, biocompatible polymers are available for biomedical applications. A large variety of reactive oligomers and highly functionalized intermediates for... 

This reaction was initially reported by Fukuyama and co-workers in 1995. It is a two-step conversion of primary amines into secondary amines via ortho-nitrobenzenesulfonation in conjunction with the Mitsunobu Reaction and subsequent removal of the o-nitrobenzenesulfonyl group by thiophenol. Therefore, this reaction is generally known as the Fukuyama amine synthesis. In addition, it is also referred to as the Fukuyama-Mitsunobu A -alkylation," Fukuyama-Mitsunobu alkylation, Fukuyama-Mitsunobu condition, Fukuyama-Mitsunobu procedure, or Fukuyama-Mitsunobu Reaction. In this reaction, the o-nitrobenzenesulfonyl-protected amine is alkylated with alcohol in the presence of PPhs and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), and the deprotection occurs in a very mild condition (almost neutral ). The o-nitrobenzenesulfonyl group is simply called the Fukuyama sulfonamide protecting groupThis reaction has become a versatile method... 

This reaction has applications in the protection of primary and secondary amino groups and selective conversion of primary amines into secondary amines. 

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