PCP via enamine intermediate [pictures]

[Nicodem]

You can't use nucleophylic substitution on tertiary halides (or pseudohalides) because they give mostly just the elimination product. The classical example thought in the school books is t-butyl-chloride which gives mostly isobutene while tBu-OH is the minor product of the solvolysis. I guess it would bee possible to use very mild conditions to give some PCP but it would always bee the in low yields.

[synthon]

2-Phenyl-2-bromopropane: A solution of 33 g of PBr3 (0.12 mol) in 55 mL of chloroform was added dropwise at 40 C to a stirred solution of 50 g of a,a-dimethylbenzyl alcohol (0.36 mol) in 700 mL of chloroform.The reaction mixture was stirred for 2 h at 40 C. The chloroform layer was separated from the viscous inorganic layer and poured into 500 mL of ice water. The organic layer was separated, washed twice with a saturated aqueous Na₂CO₃ solution and once with water, and dried over MgSO₄. The chloroform was removed under reduced pressure. After distillation a colorless liquid was obtained; boiling region 57-80 C (0.05 mmHg). The product contained 31% of the elimination product a-methylstyrene. The product was used without further purification for the synthesis of lf. The yield of 2-phenyl-2-bromopropane was 57%

a,a-Dimethylbenzylamine: This amine was obtained by treatment of 2-phenyl-2-bromopropane with liquid ammonia.^* After evaporation of the ammonia, the product was dissolved in 1 M aqueous HCl and the a-methylstyrene was extracted with diethyl ether. The water layer was brought to pH 14, and the free amine was extracted with ether. The ether layer was dried over MgSO₄, and the ether removed under reduced pressure. The yield was 53%

*: _{Brander, M. M. Red. Trm. Chim. Puys-Bus Belg. 1918,37,76-87.}

I agree, the yields are not the best..

Alcohols/Alkenes to chlorides:

A Convenient Procedure for the Quantitative Conversion of Reactive Alcohols and Olefins into the Corresponding Chlorides
Herbert C. Brown, Min-Hon Rei;
J. Org. Chem.; 1966; 31(4); 1090-1093.

..and refs in there.

[Nicodem]

Actually a yield of 53% is about two times better than I thought it is . That is quite a decent yield. But you have to consider the very low temperature used (-33°C) and the ammonia being a weaker base than piperidine. I guess piperidine in a non-polar solvent like CH2Cl2 that would inhibit carbocation formation and working at <-10°C temperature would still give about a 30% yield. And you could even recycle the 1-phenyl-cyclohexene side product.
The other bad thing is that converting the alcohol to the halide causes the same problem of H2O elimination. However, there are conditions that should give a good yield even when using conc. HCl. One is by adding a PTC catalyst because you would then have the same conditions needed for the benzylic –OH substitution as well as double bond hydrochlorination of any 1-phenyl-cyclohexene that would form from the elimination pathway.

But you still need a phenyl Grignard to prepare 1-phenyl-cyclohexanol so why should this bee any better than preparing PCP directly with the usual method?

( If you find a paper where the preparation of 1-phenyl-cyclohexene is described by the condensation of benzene and cyclohexanone then this method would prove to bee an excellent alternative. )

[ning]

Can't urea convert directly tertiary alcohols to amines in acidic conditions, by SN1 reaction, followed by hydrolysis? Yields were supposed to be good.

In this case, one would have to alkylate the amine later. I think a reductive amination with actone or methyl ethyl ketone sounds nice and attractive. Perhaps even direct alkylation with alkyl halide would work, due to steric hinderance preventing overalkylation.

Perhaps pyrolysis of PCA with pyran would give PCP directly-- if I remember correctly, one way piperazine is made is by pyrolysis of morpholine with ammonia.

[synthon]

_{Many thanks to Nicodem on the Ritter-type of reactions and their use for this purpose. At the espacenet a patent was found based on Ning's idea that tert. alcohols can be treated with urea and conc. H2SO4 to give condensation products, which upon hydrolysis give amines.}

PCA intermediate is very interesting as simple reductive amination with various ketones/aldehydes can give a spectrum of extreamly potent analogues.

Tertiary Alkyl Urea and Process for Preparing Same:

Patent US2247495

[acx01b]

in the patent, with the urea way they get seventy percent of MONO tertiary butyl urea...

but (tert-butyl)-NH-CO-NH-(tert-butyl) can exist too :-)
(why would it not exist??)
so maybe the total yield of pca from pcoh is not far from 90+ %...