Lithium compounds Amphetamines

The last of the butyl isomers, the tert-butyl compound, was made from a much more obvious starting material. This is the commercially available tert-butyl hydroquinone. It was methylated in sodium hydroxide with methyl iodide, and then carried through the above sequence (benzaldehyde. mp 124 °C from cyclohexane, nitrostyrene, yellow crystals from methanol, mp 95-96.5 °C, and lithium aluminum hydride reduction) to give 2,5-dimethoxy-4-(l,l-dimethylethyl)amphetamine hydrochloride (DOTB, mp 168 °C). Rats trained in a process called the Sidman Avoidance Schedule gave behavior that suggested that DOTB had no activity at all, and in human trials, doses of up to 25 milligrams were totally without effect. 

Synthesis. The synthesis of the amphetamine and methamphetamine derivatives in the benzobicyclo[2.2.2]-octene system has been described elsewhere (141 and references cited therein). To be able to study certain of the pharmacological aspects of these compounds, 3H-derivatives were prepared of NM-X and NM-N by reducing the N-formyl derivatives of the amphetamine analogs NH-X and NH-N with lithium aluminum tritiide (142). 

D. Enhancement of Elimination Enhancement of elimination is possible for a number of toxins, including manipulation of urine pH to accelerate renal excretion of weak acids and bases. For example, alkaline diuresis is effective in toxicity due to fluoride, isoniazid, fluoroquinolones, phenobarbital, and salicylates. Urinary acidiflcation may be useful in toxicity due to weak bases, including amphetamines, nicotine, and phencyclidine, but care must be taken to avoid acidosis and renal failure in rhabdomyolysis. Hemodialysis or hemoperfusion enhances the elimination of many toxic compounds, including acetaminophen, ethylene glycol, formaldehyde, lithium, methanol, procainamide, quinidine, salicylates, and theophylline. Cathartics such as sorbitol (70%) may decrease absorption and hasten removal of toxins from the gastrointestinal tract. 

The positional isomer of DOB with the bromine in the ortho-position is 4,5-dimethoxy-2-bromoamphetamine and is called, not surprisingly, ORTHO-DOB. It has been made by the condensation of 2-bromo-4,5-dimethoxybenzaldehyde with nitroethane to give 1-(2-bromo-4,5-dimethoxyphenyl)-2-nitropropene with a mp of 105-106 deg C. Reduction to the amphetamine had to be conducted at a low temperature and using only an equimolar amount of lithium aluminum hydride, to minimize reductive removal of the bromo group. The hydrochloride salt of 2-bromo-4,5-dimethoxyamphetamine (ORTHO-DOB) had a mp of 214-215.5 deg C, and the hydrobromide salt a melting point of 196-197 deg C or of 210 deg C. Both have been reported. The yield from the direct bromination of 3,4-DMA was apparently very bad. I do not think that the compound has ever gone into man. 

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