
This reference is for Nalorphine, morphine with an N-Allyl group instead of
the notmal N-Methyl. It is my belief that this is a GENERAL procedure that
may be applied to many simialr compounds.

Nalorphine (N-Allyl Normorphine)

35g of normorphine (Ber 63m852 (1930) or Ber 47,2312(1914) ) & 7.95g of
allyl bromide in 350cc chloroform are heated in a sealed tube at 110C for
3.5 hours. The reaction mixture is filtered & the solid residue is washed
with chloroform. The unreacted normorphine is seperated from the product
(normorphine HBr) by dissolving in water & precipitating the base with
ammonia water at a pH of 8. The yield of unreacted normorphine is 18g. The
filtrate from above is evaporated in vacuo to remove the chloroform & the
resulting residue is triturated (?) with 75cc of ether.

Cool on an ice bath for 2 hours & filter to get 9.2g of crude nalorphine.
Extract for 15 hours in a soxhet extractor with dry ether. Concentrate the
ether extract in absence of air & cool in freezer for 12 hours. The white
crystals are collected by filtration & washed with some cold ether, then
dried in vacuo to yield 5.5g pure product, m.p 208-209C. The HBr form is
obtained by dissolving the above freebase in ethanol & a slight excess if
HBr is added. The HBr will crystalize out quickly by scratching the sides
of the flask with a glass rod. The crystals are filtered off, washed with
cold alcohol & dried in vacuo. m.p. 258-259.


Commentry: This reaction produces rather a low yield. It is my opinion that
there are several side-products that cause this:

a) The HBr attacking the 7-8 double bond.
b) The Allyl bromide forming an ether with the 3 & 6 OH groups of the morphine.
c) Apomorphine transformation due to acidic/hot conditions.)

If we go back & examine thy hydrocodone structure we find...

a) the 7-8 bond is reduced and so cannot be attacked.
b) the 3 OH is protected by a methyl ether.
c) the 7-8 bond reduction prevents apomorphone transformation.

It is my opinion that hydrocodone will result in MUCH higher yields. In
fact, I think allyl bromide (rather than the iodide) was used BECAUSE the
resulting HI would attack the double bond.

Comments on this stuff gratefully recieved!

A.N
