Cyclohexylamines

Crystalline solid m.p. 35-36 "C, b.p. 154--156 C, prepared by oxidizing A,A -dicycIo-hexylthiourea with HgO in carbon disulphide solution, also obtained from cyclohexylamine and phosgene at elevated temperatures. Used as a mild dehydrating agent, especially in the synthesis of p>eptides from amino-acids. Potent skin irritant. 

This procedure has been performed in a variety of ways [28 p714, 38-42] with variations in solvent, base and time of reaction. For piperonal conversion, the consensus is toward the use of acetic acid as the solvent, ammonium acetate as the base and 4 hours of reflux time. Dr. Alexander Shulgin, a giant in this field, prefers the use of cyclohexylamine as the base. Strike would not tend to doubt this man s choice, especially since Strike is also getting the... 

The heterocyclic rings in quinoline (116) and isoquinoline are selectively reduced by Pd on carbon-catalyzed reaction of ammonium formatc[107]. Some benzene rings are also reduced. For example, nitrobenzene is reduced to cyclohexylamine (117) with formic acid. It is important to use a sevenfold excess of formic acid[108]. 

The equilibrium shown m the equation lies to the right =10 for proton transfer from the conjugate acid of aniline to cyclohexylamine making cyclohexylamine 1 000 000 times more basic than aniline... 

Identify the principal organic products of each of the following reactions (a) Cyclohexanone + cyclohexylamine-------------->... 

Reductive amination of cyclohexanone using primary and secondary aHphatic amines provides A/-alkylated cyclohexylamines. Dehydration to imine for the primary amines, to endocycHc enamine for the secondary amines is usually performed in situ prior to hydrogenation in batch processing. Alternatively, reduction of the /V-a1ky1ani1ines may be performed, as for /V,/V-dimethy1 cyclohexyl amine from /V, /V- di m e th y1 a n i1 i n e [121 -69-7] (12,13). One-step routes from phenol and the alkylamine (14) have also been practiced. 

Dicyclohexylarnine may be selectively generated by reductive alkylation of cyclohexylamine by cyclohexanone (15). Stated batch reaction conditions are specifically 0.05—2.0% Pd or Pt catalyst, which is reusable, pressures of 400—700 kPa (55—100 psi), and temperatures of 75—100°C to give complete reduction in 4 h. Continuous vapor-phase amination selective to dicyclohexylarnine is claimed for cyclohexanone (16) or mixed cyclohexanone plus cyclohexanol (17) feeds. Conditions are 5—15 s contact time of <1 1 ammonia ketone, - 3 1 hydrogen ketone at 260°C over nickel on kieselguhr. With mixed feed the preferred conditions over a mixed copper chromite plus nickel catalyst are 18-s contact time at 250 °C with ammonia alkyl = 0.6 1 and hydrogen alkyl = 1 1. 

Methylenediandine (4) (MDA) /7(9/-77-5 7hydrogenation to methylenedi(cyclohexylamine) generates first the <7j -(6) and trans-Q isomers of half-reduced 4-(7-aminohen7y1)-cyc1ohexy1amine (5) [28480-77-5] a differentially reactive diamine offered ia developmental quantities by Air Products and Chemicals. 

Direct production of select MDCHA isomer mixtures has been accompHshed usiag mthenium dioxide (30), mthenium oa alumiaa (31), alkah-moderated mthenium (32) and rhodium (33). Specific isomer mixtures are commercially available from an improved 5—7 MPa (700—1000 psi) medium pressure process tolerant of oligomer-containing MDA feeds (34). Dimethylenetri(cyclohexylamine) (8) [25131 -42-4] is a coproduct. 

Batch syntheses comparable to those used for MDA produce 3,3 -dimethy1methy1enedi(cyclohexylamine) marketed under the trade name Laromia C-260. The starting aromatic diamiae, 3,3 -dimethy1methy1enediani1ine [838-88-0] is prepared from o-toluidine [95-53-4] condensation with formaldehyde. Similarly 3,3 -dimethyldicyclohexylaniiae [24066-10-2] may be produced (38) from o-toHdine [119-93-7] derived from o-nitrotoluene [88-72-2]. The resultant isomer mixtures are dependent on reduction conditions as ia MDA hydrogeaatioa. 

Cycloahphatics capable of tertiary carbocation formation are candidates for nucleophilic addition of nitriles. HCN in strong sulfuric acid transforms 1-methyl-1-cyclohexanol to 1-methyl-1-cyclohexylamine through the formamide (47). The terpenes pinene (14) [2437-95-8] and limonene [5989-27-5] (15) each undergo a double addition of HCN to provide, after hydrolysis, the cycloahphatic diamine 1,8-menthanediamine (16) (48). 

Production of cyclohexylamine reflects this balance of raw material versus operating cost stmcture. When aniline cost and availabiUty are reasonable, the preferred route is aniline ring reduction alternatively the cyclohexanol amination route is chosen. 

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