Dehydrogenation amines

Amination under these homogeneous conditions is an important breakthrough in oxidative amination-dehydrogenation procedures. It has been predicted that If these new oxidative aminations can be performed on a larger scale without any explosion hazard, they might be very useful preparatively (90AHC(49)117). 

For benzylamine (entry 8) the arylation reaction with m-trifluoromethylbenzene remains the main process (yield 46 %). The only other fluorinated product observed, but the starting compound, is the trifluoromethylbenzene (29 %). In a parallel way, the arylation reaction is apparently accompanied by a partial amine dehydrogenation into the corresponding imine 1, whose formation could explain the presence of N-benzylidene benzylamine 2, and dibenzylamine 2, this last one being detected in small amount. These results are described in the Scheme 1 in which the nickel complex could act as a catalyst for the (de)-hydrogenation processes (refs. 10, 11). 

Scheme 1. Amine dehydrogenation catalyzed by nickel complexes.

Secondaiy alcohols have been shown to be competent reaction partners for the preparation of tertiaiy amines, but typically require higher temperatures. Beller and co-workers reported a method for the synthesis of cx-branched tertiary amines via N-all lation of secondary amines with secondaiy alcohols using catalytic Ru3(CO)i2 with JV-phenyl-2-(dicyclo-he)ylphosphanyl)pyrrole ligand (Scheme 12.6). The scope is limited to the adulation of cyclic amines as acyclic amines undergo trans-alkylation, likely due to competitive amine dehydrogenation. 

Metal-catalysed amine dehydrogenation has been utilised for quinoline preparation. Shim and Cho have reported the union of 2-amino ben l alcohol with secondary alcohols in the presence of catalytic RuCl2(PPh3)3 at 80 °C to afford quinolines (Scheme 12.40). The mechanism may involve transfer of hydrogen from both alcohol reactants to dodecene (a sacrificial hydrogen acceptor) to provide the corresponding carbonyls. In the absence of dodecene, only trace product is formed evaluation of other hydrogen acceptors was not described. KOH-induced aldol condensation followed by cyclodehydration would provide the observed quinolines. 

This is an example of the Doebner synthesis of quinoline-4-carboxylic acids (cinchoninic acids) the reaction consists in the condensation of an aromatic amine with pyruvic acid and an aldehj de. The mechanism is probably similar to that given for the Doebner-Miller sj nthesis of quinaldiiie (Section V,2), involving the intermediate formation of a dihydroquinoline derivative, which is subsequently dehydrogenated by the Schiff s base derived from the aromatic amine and aldehyde. 

Alkyl groups attached to aromatic rings are oxidized more readily than the ring in alkaline media. Complete oxidation to benzoic acids usually occurs with nonspecific oxidants such as KMnO, but activated tertiary carbon atoms can be oxidized to the corresponding alcohols (R. Stewart, 1965 D. Arndt, 1975). With mercury(ll) acetate, allyiic and benzylic oxidations are aJso possible. It is most widely used in the mild dehydrogenation of tertiary amines to give, enamines or heteroarenes (M. Shamma, 1970 H. Arzoumanian. 1971 A. Friedrich, 1975). 

A method for making ben2onitri1e by dehydrogenation of the Diels-Alder adduct of butadiene and acrylonitrile also has been described (79). Ben2onitri1e also can be made on a small scale by the dehydration of ben2amide ia an iaert solvent with phosphoms oxychloride or ben2enesulfonyl chloride and an organic amine (80,81). 

Heating butanediol or tetrahydrofuran with ammonia or an amine in the presence of an acidic heterogeneous catalyst gives pyrroHdines (135,136). With a dehydrogenation catalyst, one or both of the hydroxyl groups are replaced by amino groups (137). 

Like mthenium, amines coordinated to osmium in higher oxidation states such as Os(IV) ate readily deprotonated, as in [Os(en) (NHCH2CH2NH2)] [111614-75-6], This complex is subject to oxidative dehydrogenation to form an imine complex (105). An unusual Os(IV) hydride, [OsH2(en)2] [57345-94-5] has been isolated and characterized. The complexes of aromatic heterocycHc amines such as pyridine, bipytidine, phenanthroline, and terpyridine ate similar to those of mthenium. Examples include [Os(bipy )3 [23648-06-8], [Os(bipy)2acac] [47691-08-7],... 

When additional substituents ate bonded to other ahcycHc carbons, geometric isomers result. Table 2 fists primary (1°), secondary (2°), and tertiary (3°) amine derivatives of cyclohexane and includes CAS Registry Numbers for cis and trans isomers of the 2-, 3-, and 4-methylcyclohexylamines in addition to identification of the isomer mixtures usually sold commercially. For the 1,2- and 1,3-isomers, the racemic mixture of optical isomers is specified ultimate identification by CAS Registry Number is fisted for the (+) and (—) enantiomers of /n t-2-methylcyclohexylamine. The 1,4-isomer has a plane of symmetry and hence no chiral centers and no stereoisomers. The methylcyclohexylamine geometric isomers have different physical properties and are interconvertible by dehydrogenation—hydrogenation through the imine. 

The 1,4-isomer has been similarly generated from terephthalonitdle [623-26-7] (56) using a mixed Pd/Ru catalyst and ammonia plus solvent at 125 °C and 10 MPa (100 atm). It is also potentially derived (57) from terephthaUc acid [100-21-0] by amination of 1,4-cyclohexanedimethanol (30) [105-08-8], Endocyclization, however, competes favorably and results in formation of the secondary amine (31) 3-a2abicyclo[3.2.2]nonane [283-24-9] upon diol reaction with ammonia over dehydration and dehydrogenation catalysts (58) ... 

A variant on this structure, dioxyline, has much the same activity as the natural product but shows a better therapeutic ratio. Reduction of the oxime (113) from 3,4-dimethoxyphenyl-acetone (112) affords the veratrylamine homolog bearing a methyl group on the amine carbon atom (114). Acylation of this with 4-ethoxy-3-methoxyphenyl acetyl chloride gives the corresponding amide (115). Cyclization by means of phosphorus oxychloride followed by dehydrogenation over palladium yields dioxyline (116). ... 

Likewise, 5-phenyl-1/7-3-benzazepin-2(3//)-ones, e.g. 32, prepared by dehydrogenation of the tetrahydro derivatives 31 with 2,3-diehloro-5,6-dieyano-l,4-benzoquinone (DDQ), on treatment with Meerwein s reagent yield the 2-ethoxy derivatives, e.g. 33, which undergo facile aminodeethoxylation with a variety of amines.211... 

Purely parallel reactions are e.g. competitive reactions which are frequently carried out purposefully, with the aim of estimating relative reactivities of reactants these will be discussed elsewhere (Section IV.E). Several kinetic studies have been made of noncompetitive parallel reactions. The examples may be parallel formation of benzene and methylcyclo-pentane by simultaneous dehydrogenation and isomerization of cyclohexane on rhenium-paladium or on platinum catalysts on suitable supports (88, 89), parallel formation of mesityl oxide, acetone, and phorone from diacetone alcohol on an acidic ion exchanger (41), disproportionation of amines on alumina, accompanied by olefin-forming elimination (20), dehydrogenation of butane coupled with hydrogenation of ethylene or propylene on a chromia-alumina catalyst (24), or parallel formation of ethyl-, methylethyl-, and vinylethylbenzene from diethylbenzene on faujasite (89a). 

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