Syntheses of THC and Analogs

This method gives about 50% yield for THC and about 90% for the I. l -dimethylpentyl analog. 

Olivetol 4.74 g (or equimolar amount of analog), 4.03 g (+) cis or trans p-methadien (2,8)-ol-l (the racemic compound can be used but yield will be one-half), 0.8 g p-toluenesulfonic acid in 250 ml benzene reflux two hours (or use 0.004 Moles tri-fluoroacetic acid and reflux five hours). Cool, add ether, wash with NaHCOj and dry, evaporate in vacuum to get about 9 g of mixture (can chromatograph on 350 g silica gel- benzene elutes the THC benzene ether 98 2 elutes an inactive product then benzene ether 1 1 elutes unreacted olivetol evaporate in vacuum to recover olivetol). 

Dissolve the olivetol or analog and p-menthadienol or p-metha-triene (1,5,8) in 8 ml liquid SOj in a bomb and fuse 70 hours at room temperature. Proceed as above to get about 20% yield. 

In the synthesis of THC with verbenol, the cis isomer is preferable to the trans since the latter decomposes at room temperature. Pinene or carvone give active THC s [JMC17,287(74)]. 

IM (+)-trans-2-carene oxide (2-epoxycarene), IM olivetol or analog, 0.05 M p-toluenesulfonic acid in lOL benzene reflux two hours and evaporate in vacuum (or can separate the unreacted olivetol as above) to get about 30% yield THC. Olivetol can also be separated as described below. For synthesis of 2-epoxycarene (A carene oxide) from A carene (preparation given later) see 

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