Secondary Amines to Imines

Secondary amines having hydrogens on the a carbon are dehydrogenated to imines by mercuric acetate or manganese dioxide [825, 1091]. Piperidines give A -piperideines [1091] (equations 511 and 512). 

Dihydropyridine derivatives resulting from the Hantzsch synthesis are dehydrogenated to pyridines by heating with a dilute mixture of nitric acid and sulfuric acid (yields 58-65%) [ 5S] (see equation 41). 

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Oxidative dehydrogenations of many macrocyclic ligand complexes have now been documented. Typically, these reactions involve conversion of coordinated secondary amines to imine groups. 

Abstract This chapter principally concerns oxidations of organic substrates containing N, O, S, P, As and Sb. Oxidations of amines are covered first, including primary amines to nitriles or amides secondary amines to imines or other products tertiary amines to N-oxides or other prodncts (Section 5.1) and the oxidation of amides (5.2). Oxidation of ethers to esters or lactones follows (5.3), then of sulfides to sulfoxides or sulfones (5.4) and of phosphines, arsine and stibines to their oxides (5.5). A final section (5.6) concerns such miscellaneous oxidations not covered by other sections in the book. 

Primary amines at a primary carbon can be dehydrogenated to nitriles. The reaction has been carried out with a variety of reagents, among others, IF5,"9 lead tetraacetate, 20 nickel peroxide,121 NaOCl in micelles,122 S g-NiSO, 2-1 and CuCl-02-pyridine.124 Several methods have been reported for the dehydrogenation of secondary amines to imines.125 Among them126 are treatment with(l) iodosylbenzene PhIO alone or in the presence of a ruthenium complex, 27 (2) Me2SO and oxalyl chloride, 2" and (3) f-BuOOH and a rhenium catalyst. 29... 

Oxidation of amines.1 The radical effects oxidation of primary or secondary amines to imines at 25° (4-8 hours). The products are generally isolated as the dinitrophenylhydrazones of the corresponding carbonyl compounds. 

The oxidation of secondary amines to imines can be carried out by hydrogen transfer reaction under mild conditions using a catalytic amount of 9/2,6-dimethoxy benzo-quinone/Mn02 (Eq. 3.30) [65]. 

Secondary amines can be converted into the corresponding imines, in a highly efficient single step, upon treatment with 2 equiv. of t-BuOOH in benzene in the presence of RuCl2(PPh3)3 catalyst at room temperature [134]. This is the first catalytic oxidative transformation of secondary amines to imines, which are hardly accessible by conventional methods. A 4A molecular sieve is needed to prevent the hydrolysis of product imines in some cases. The oxidations of tetrahydroisoquinoline 61 and allylamine 63 gave the corresponding cyclic imine 62 and azadiene 64 in 98% and 80% yields, respectively (Eqs. 3.75 and 3.76). 

Ru2(II,II) complexes are known to catalyze hydrogenation of alkenes and alkynes [235], cross-metathesis of alkenes [198], and intermolecular insertion of diazo compounds into 0-H bond [236]. Ru2(II,III) complexes catalyze the oxidative transformation of secondary amines to imines [237], aerobic oxidations of alcohols... 

The catalytic system consisting of (n-Pr4N)(Ru04) and N-methylmorpholine N-oxide (NMO) can be also used for oxidative transformation of secondary amines to imines (Eq. (7.55)) [106]. 

Backvall et al. found that the ojddation of secondary amines to imines can be performed by a hydrogen transfer reaction under mild conditions in the presence of 2,6-dimethoxybenzoquinone and the ruthenium catalyst 29 (Eq. (7.58)) [108]. 

A similar mechanism has been proposed for the oxidation of secondary amines to imines using catalytic Ru2( i-02CMe) Cl and O2 in toluene [108]. The substrate scope includes a number of five- and six-membered cyclic amines, including tetrahydroquinolines, tetrahydroisoquinolines, and indolines. Dibenzylamine converted cleanly to the imine. Of interest, the primary amine benzylamine is oxidized completely to benzonitrile. Several monoruthenium complexes were also evaluated for catalysis, but their reaction yields were significantly lower, supporting an intact diruthenium catalyst. 

A -demethylation (A-dealkylation) of alkylamines such as aminopyrine, A -methylbarbital, and A,A-dimethylaniline is the typical reaction catalyzed by P-450 and peroxidases [225-227]. Biomimetic oxidation of alkyl amines catalyzed by metalloporphyrins is known to yield A-dealkylated products (Scheme lOA) [228-233]. While the dealkylation reactions are the major pathway in the alkyl amine oxidation, Larsen and Jprgensen reported the oxidation of secondary amines to imines by iodosylbenzene catalyzed by Mn (TPP), Fe (TPP), and Mn (salen) (Scheme lOB) [234]. Similar A -dealkylation of A-nitrosodibenzylamine to benzaldehyde and benzyl alcohol was demonstrated by Lindsay Smith et al. as model reactions of carcinogenic A-nitrosodialkylamine metabolism by P-450 [235]. 

A similar dehydrogenation of an amine (primary or secondary amine) to imine with catalyst 1 was used by Beller to alkylate indoles (9) [50]. The imine reacts with the indole to give an aminoalkylated intermediate, which undergoes elimination of ammonia or amine to give an oxidized indole intermediate. The hydrogens removed from the amine are now added back to the latter intermediate to give the indole product so in this case the overall reaction is not an oxidation. 

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