Recently I found some more interesting stuff about my favourite field of research in the library:
Helvetica Chimica Acta, 40 (1957), p. 1232-1441, and J. Hellerbach and O. Schnider - '138. Hydroxy-morphinane (11. Mitteilung)'
It contains experimental procedures for N-arylalkyl-morphinanes, as well as some physical data and confirms the high activity of the N-phenethyl compounds (up to 50 - 70 x morphine). N-phenylpropyl compounds are stated to have weak effects, the phenylbutyl compounds being somewhat more active. All this confirms the activity data posted recently. I will translate the more interesting parts now, starting from p. 1235 - all elemental analysis data is omitted:
Experimental PartFor each method only one method is described in detail.
Method A (-)-3-Hydroxy-N-phenylethyl-morphinane. 70 g (+)-1-p-Hydroxybenzyl-1,2,3,4,5,6,7,8-octahydro-isochinoline are dissolved in 350 ml DMF and after addition of 40 g anhydrous K2CO3, 53.2 g beta-phenylethyl-bromide are added dropwise with stirring. The reaction product is stirred overnight in an oil bath having a temperature of 100 °C, mostly freed of DMF at waterpump-pressure and dissolved in ether. The ethereal solution is washed with water, dried with anhydrous Na2SO4 and the ether is distilled off. The remaining base (ca. 100 g), dissolved in acetone, immidiatelly yields (-)-1-p-Hydroxybenzyl-2-phenylethyl-1,2,3,4,5,6,7,8-octahydro-isochinoline oxalate upon addition of oxalic acid, and melts at 158 - 159 °C from i-PrOH. [alpha]22D = - 55 ° (c = 1 in MeOH).
Hydrobromide: mp 203 - 205 °C (from EtOH-ether), [alpha]21D = - 47.3 ° (c = 1 in MeOH)
100 g (-)-1-p-Hydroxybenzyl-2-phenylethyl-1,2,3,4,5,6,7,8-octahydro-isochinoline oxalate are heated with stirring with 500 g 99 % crystalline H3PO4 at 140 °C (reaction temperature) for 72 h, carefully diluted with 1200 ml water afterwards and then boiled for another hour. The reaction mixture is cooled, 600 ml n-BuOH are added on top ['überschichten'] and conc. NH3 is added dropwise with stirring until the mixture is slightly alkaline to phenolphtaleine at such a rate that the neutralization temperature is 50 - 60 °C. After cooling ca. 400 ml benzene are added, the aqueous phase is removed from the benzene-butanol layer and the latter is washed neutral with water. Upon distilling off the benzene-butanol mixture in vacuo the base crystallizes. Recrystallized from DMF the (-)-3-Hydroxy-N-phenylethyl-morphinane melts at 243 - 245 °C.
Hydrobromide: mp. 300-301 °C (from water-EtOH), [alpha]20D = - 63.12 °, (c = 3,27 in MeOH).
[? can't read if D or L]-tartrate. 1 H2O: mp. 125 - 126 °C (from i-PrOH), [alpha]20D = - 42.75 ° (c = 0.983 in water).
Phosphate: mp. 190 - 192 °C (from water)
Camphorsulfonate: mp. 218 - 220 °C (from water)
Methyl-'onium-bromide: mp. 239 - 240 °C (from EtOH), [alpha]20D = - 42.81 ° (c = 1.155 in MeOH)
This is it for now, more will bee presented some other day. I think the use of p-hydroxybenzyl-1,2,3,4,5,6,7,8-octahydro-isochinoline instead of the methoxy-derivative as starting material has mainly to do with chirality, the latter should work too, shouldn't it? That would make phenomorphan just as accessible as dromoran
.
P.S.: I just noticed that I have been promoted to hive bee from new bee, that's very nice
!