Cyclohexanone—continued alkylation

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. 

Treatment of 6-ethoxy-2-phenyl-3-carboxy-5,6-dihydro-4/7-pyran with hydroxylamine transforms the heterocycle to 2-phenylnicotinate <97JHC93>. However, an isoxazole is obtained if the pyran is substituted with an acyl group rather than the ester functionality. Nitriles continue to be key components in pyridine synthesis. The bicyclic ketal 8 is converted cleanly to the pyridine 9 in the presence of an alkyl nitrile using 5 equiv of TMSOMs and 1 equiv of BFrEt20. This combination, generating the active ingredient boron difluoromethanesulfonate, avoids the byproduct cyclohexanones <97JHC325>. 

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