Allyl bromide Nalorphine

The prototype of this series is synthesized by first reacting morphine with cyanogen bromide. This reagent in effect serves to replace the methyl group by cyano. Hydrolysis of the intermediate (11) affords desmethylmorphine (12). Alkylation of the last with allyl bromide affords nalorphine (13). ... 

The A -allyl derivative nalorphine (3-2) is prepared from A -demethylmorphine (3-1) by alkylation with allyl bromide [2]. The discovery that this compound proved to antagonize the activity of morphine in experimental animals led to the synthesis of the potent opioid antagonist naloxone (8-3), which is discussed below. Nalorphine (3-2), in marked contrast to the latter, does show some modest analgesic activity in humans. 

As with morphine and the benzomorphans, variation of the N-substituent (Chapters 2 and 4) markedly affects opioid pharmacodynamic activity, and (—) 49 (R = OH R = allyl) known as levallorphan or Lorphan is an antagonist several times more potent than nalorphine. Rather than prepare levallorphan by the N-demethylation 49, (R = OH R = Me) and allylation, on a commercial scale 51 (R and R = H) or 51 (R = H R = CH2C6H5) are obtained optically pure.(34) The former may be allylated and cyclized, whereas the latter was cyclized, debenzylated by hydrogenolysis, and finally converted to levallorphan with allyl bromide. 

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