Conversion to primary amines

Oximes generally require strong reducing agents to undergo complete conversion to primary amines (Entry 8, Table 10.8) the use of weaker reducing reagents, such as borane, leads mainly to the formation of hydroxylamines (see Section 10.3). 

Hydrazine derivatives, reduction 68 Hydrazones, conversion to primary amines 69 oxidation 710... 

Leuckart reaction The conversion of ketones and aromatic aldehyde,s to primary amines by reaction with ammonium methanoale at a high temperature. 

The rate of reaction slows down as the conversion to tertiary amine increases and primary amine concentrations drop below 1%. Conversion to 100% tertiary amine is difficult. 

Other sequences that transform primary alcohols to primary amines include (a) conversion of the alcohol to a cyanate, rearrangement to an isocyanate, and hydrolysis,3 and (b) conversion of the alcohol to an -V alkylformamide via the Ritter reaction, followed by hydrolysis.4... 

Normally the reaction Is useful for the conversion of alkyl halides to primary amines without concomitant formation of secondary amines.29 Treatment of polymer 17 with hexamethylenetetramine in a mixture of ethanol/THF afforded an insoluble resin. Using diazabicyclooctane (DABCO), we demonstrated that the reaction could be limited to attack by a single nitrogen in a multifunctional amine, so we did not anticipate crosslinking via bis-quat salt formation. Hydrolysis of 2 with anhydrous HC1 in ethanol generated free amino groups as evidenced by a positive ninhydrin test, but quantitative hydrolysis could not be achieved and the product remained insoluble. One would have expected a simple bis-quat to hydrolyse and open the crosslinked structure. 

Reduction of azides is a classical approach to primary amine synthesis. Treatment of 17 with sodium azide in DMF or in THF/H2O mixtures in the presence of phase transfer catalysts effects a quantitative conversion to the corresponding polymeric azide, 27. Recently the reduction of azides to primary amines via hydrolysis of iminophosphoranes produced by interaction of the azide with triethyl phosphite was reported.30 Application of this technique to the azidomethyl polymer, 27, as shown below, failed to produce a soluble polyamine. 

Supported Co, Ni, Ru, Rh, Pd and Pt as well as Raney Ni and Co catalysts were used for the hydrogenation of dodecanenitrile to amines in stirred SS autoclaves both in cyclohexane and without a solvent. The reaction temperature and the hydrogen pressure were varied between 90-140 °C and 10-80 bar, respectively. Over Ni catalysts NH3 and/or a base modifier suppressed the formation of secondary amine. High selectivity (93-98 %) to primary amine was obtained on Raney nickel, Ni/Al203 and Ru/A1203 catalysts at complete nitrile conversion. With respect to the effect of metal supported on alumina the selectivity of dodecylamine decreased in the order Co Ni Ru>Rh>Pd>Pt. The difference between Group VIII metals in selectivity can be explained by the electronic properties of d-band of metals. High selectivity to primary amine was achieved on base modified Raney Ni even in the absence of NH3. 

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. 

Substituted hydroxylamines 1-5 (R = R = H) and their A-mono- or A,A-disub-stituted derivatives 1-5 have been used extensively for electrophilic amination of both carbanions and enolates since the first report in 1938 on the use of 0-methylhydroxylamine 1 (R = Me) for conversion of Grignard reagents to primary amines. Oximes 7 (Z = H) have found limited applicability as amination reagents for carbon nucleophiles and then-use was first reported in 1907. Ketone 0-sulfonyloximes 7 (Z = SO2R) have recently been developed. 

Alvernhe and Laurent first developed a procedure for conversion of Grignard reagents to primary amines using acetone oxime 6c and butanone oxime 6d (Scheme 55) 22 23 However, the yields were low. They expanded their study to investigate how well organo-lithiums perform in their reaction with 6c or 6d 23. Phenyllithium gave a 1 4 mixture of aniline and the addition product of phenyllithium to the imine (Scheme 53, path e product) in the reaction with 6c while aziridine was obtained in the reaction with 6d (Scheme 56). 

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 hydroboration amination sequence in diglyme is a general procedure for the conversion of olefins to primary amines without rearrangement and with predictable stereochemistry.5 An alternative procedure, using tetrahydrofuran as solvent and either hydroxylamine-O-sulfonic acid or chloramine, is applicable with terminal olefins and relatively unhindered internal and alicyclic olefins.6 O-Mesitylenesulfonylhydroxylamine also gave desired amines in comparable yield.7 Alternative procedures for the hydroboration of olefins use commercially available solutions of di-borane in tetrahydrofuran8 or dimethylsulfide.9... 

Conversion of Alkyl Halides to Primary Amines with Hexamethylenetetramine Amino-de-halogenation (overall transformation)... 

Another way to oxidize primary alkyl halides to aldehydes is by the use of hexamethylenetetramine followed by water. However, this reaction, called the Sommelet reaction. is limited to benzylic halides. The reaction is seldom useful when the R in RCH2CI is alkyl. The first part of the reaction is conversion to the amine ArCH2NH2 (0-44), which can be isolated. Reaction of the amine with excess hexamethylenetetramine gives the aldehyde. It is this last step that is the actual Sommelet reaction, though the entire process can be conducted without isolation of intermediates. Once the amine is formed, it is converted to an imine (ArCH2N=CH2) with formaldehyde liberated from the reagent. The key step then follows transfer of hydrogen from another mole of the arylamine to the imine ... 

The same reduction methods may be applied to the conversion of nitriles to primary amines. 

An example of the use of an X—Y reagent is conversion of alkylboranes to primary amines with hydroxylaminesulfonic acid, H2NOSOsH (Equation 11-4). The key steps are attack of the nucleophilic nitrogen at boron,... 

OPA (ortho-phthalaldehyde) Aex = 340 nm, Aem = 455 nm. Derivatives are not stable (minutes). OPA is best used as a postcolumn derivatizing reagent. Precolumn use necessitates well-controlled and automated (mechanized) handling of the sample/reagents to ensure uniformity of time elapsed from reaction to injection. It reacts with primary amines only. Proline can be detected only if first converted to primary amine by oxidative reagents like chloramine T or sodium hypochlorite. Conversely, the concomitant reaction with OPA followed by FMOC obviates this problem and is the basis of the AminoQuant system marketed by Hewlett-Packard... 

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-... 

A rhodium catalyst [Rh(cod)Cl]2 was applied at 140°C and 100 bar to achieve a yield of 99% in hydroaminomethylation of ethyl oleate and morpholine. Several amines were tested in the reaction with fatty compounds hexylamine, benzylamine, aspartic diethyl acid, valinol, and diisopropylamine are further amines which can be employed in hydroaminomethylation. The conversion with primary amines showed that hydroaminomethylation can proceed twice on the amine. The dimer fatty acid ester bridged with an amine is a highly functionalized molecule with various applications. An excess of the primary amine during the reaction prohibits the reaction of the hydroformylation product with a secondary amine which is the product of hydroaminomethylation with the primary amine (Scheme 19). 

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