This requires a little knowledge in handling before attempts are to be made at reducing. Here are some things to remember.
1. Sodium borohydride and sodium cyanoborohydride have been known to explode upon removal of a screw cap from a glass bottle.
38 RECREATIONAL DRUGS
3. Lithium aluminum hydride squeezed, or smashed, may cause a fire.
4. Contact of lithium aluminum hydride with water may cause fire or explosion.
5. Borane (sometimes called diborane) ignites when in contact with air, so it must be covered with tetrahydrofuran, always.
6. Contact with water may ignite sodium aluminum hydride.
A Typical Lithium Aluminum Hydride Reduction. JACS, 72, 2781 (1950). To a well stirred
mixture of 53 g lithium aluminum hydride (LAH) and 2500 ml of dry ether is added 55 g of 4-hydroxy-3-methoxy-B-nitrostyrene (or equimolar ratio of nitropropene or analog) in 150 ml of dry ether over an hour and 20 min. Stir and reflux for about 9 hours, taking care to exclude all moisture. Cool and add 3000 ml of ice cold 1.5 N sulfuric acid dropwise with good stirring (the acid addition can be speeded up after about half of it has been added). The water layer is separated and its pH adjusted to 6 with solid lithium carbonate. This solution is heated to boiling and the aluminum hydroxide that precipitates is filtered off. The hot filtrate is mixed with a solution of 70 g of picric acid in the minimum amount of hot ethanol that it takes to dissolve the picric. Let stand for 4 hours, filter and recrystallize from water.
88 g of the above picrate product in 1 liter of water is mixed with 400 ml of coned hydrochloric acid. The picric acid which precipitates is filtered off and the filtrate is extracted with nitrobenzene and then with ether (extra ether extracts may eliminate the need for nitrobenzene). The aqueous solution is evaporated (reduced pressure is fastest) to dryness, dissolved in methanol-ethyl acetate, and filtered hot. You may filter off the crystals before they reach complete dryness if you would like to sample a little while waiting. Yield, 90%. This is a gentle reduction made from Tyramine, but it can be used on most any reducible forms. See the amphetamines chapter for formula (JACS, 72, 2781, 1950) of 4-hydroxy-3-methoxy-B-nitrostyrene and analogs. For a reduction using the reverse addition of LAH and several other reductions see the amphetamine chapter.
A Reduction With Aluminum Hydride (Alane). In a three necked 1 liter flask equipped with
a gas tight mechanical stirring device, an addition funnel, and a long reflux condenser, is charged with 0.1 mole (3.8 g) of LAH and 100 ml of dry ether. Add a solution of 0.1 mole (13.3 g) of aluminum chloride (dry or anhydrous) rapidly through the dropping funnel, continuing the stirring the entire time. After five min, add 0.1 mole (16.3 g) of nitrostyrene, or analog (see amphetamines section), in 200 ml of ether to the well stirred reaction, dropwise. One hour after the nitrile addition add dropwise enough water (until the bubbling stops) to decompose the excess hydride (or halide). Then add 140 ml of 6 N sulfuric acid diluted with 100 ml of water. Separate the ether layer and extract the aqueous layer with 4 100 ml portions of ether. After cooling the aqueous layer is alkalized with powdered KOH to pH 11, diluted with 600 ml of water, and extracted with four 100 ml portions of ether. The combined ether extracts are stirred with Drierite and evaporated under reduced pressure. The residue (21.5 g) is distilled to give corresponding product. Although there is no reference for this method, the yield is 90%.
Sodium Reductions, Reductions using sodium are becoming increasingly rare, but they do exist.
In case you should find a formula requiring a sodium amalgam, I have given the preparation.
Sodium Amalgam. 5 g of clean sodium are cut into 3-5 mm squares. Each individual cube
is placed on the surface of 245 g of mercury in a dish and held underneath the mercury with a glass spoon until dissolved. The remaining sodium cubes are treated the same way, as soon as possible. After the sodium has been added, the mixture is allowed to cool, solidify, and then is crushed. Store in a closed bottle.
Reductions 39
This reaction is highly exothermic, so heat is normal. If the formula does not specify the sodium amalgam then do not use it (e.g., the first formula in the amphetamines chapter).
Reduction with LAH and Aluminum Chloride. This gives some of the best yields possible, of
all reductions known to me. It is designed to reduce phenylacetonitriles but may also be used to give high yields with reductions of nitropropenes, etc. It is used for reducing diphenylacetonitrile (see analgesics, the Amidone formula, for the synthesis of diphenylacetonitrile), to give diphenylethylamine; however, phenylacetonitrile may also be used to give phenethylamine (see precursors section to get several different formulas for phenylacetonitrile).
JACS, 77, 2544 (1955). In a 1 liter 3 necked flask fitted with a mercury sealed stirrer, a reflux
condenser, and an addition funnel, is placed a solution of 0.1 mole of LAH in 100 ml of dry ether. Through the dropping funnel, a solution of 0.1 mole (13.3 g) of aluminum chloride in 150 ml of dry ether, is added to the LAH solution rapidly. Next a solution of 0,1 mole (19.3 g) of diphenylacetonitrile (or an equimolar amount of analog) in 200 ml of dry ether is added dropwise to the well stirred mixture. An evolution of hydrogen should be noted. After the addition is complete, continue stirring for 1 hour, then add water to decompose the excess hydride. Add 140 ml of 6 N sulfuric acid and 100 ml of water. Separate the ether layer and extract the aqueous layer in an ice-water bath and add KOH until the pH is 11, then extract with four more 100 ml portions of ether after diluting with 600 ml of water. Combine the ether extracts, dry over Drierite and evaporate the ether off. Fractionally distill through a 12 inch column at about 184° using 17 mm of vacuum. Yield: 91%.
Note: Always add water slowly to hydride type substances when decomposing them; when
40 RECREA 7TONAL DRUGS
AMPHETAMINES
This chapter contains all the goodies so dear to all you speed freaks. It also contains several formulas for mescaline. I chose to put mescaline in this chapter instead of the hallucinogen section because the mescaline molecule is basically the same as any amphetamine. It is correct to say that mescaline is the grampa of speeders and the relation is obvious by the similarity of their synthesis. Whether you call it phenethylamine, amphetamine, phenyisopropylamine, aminoethylbenzene, phenylaminopropane, desoxyephedrine, etc., the molecule is good old mes- caline with a few minor changes. However, these minor changes can cause drastic changes in activity and psychotomimetic effects.
The criteria of molecular structure of amphetamine-like compounds are a benzene ring with
an aliphatic chain of two or three carbon atoms with an amino-group (-NH2) on the second or
b carbon atom. There are exceptions to this rule (Tuamine, and Privine, etc.), but generally we will need a benzene ring to use as starting material for our speed. What kind of benzene ring? Some formulas call for allyl benzene, but most require you to change the allyl to propenyl benzene. Then we must nitrate the benzene ring with lovely things like rocket fuel. (Now can you see why I want you to purify as specified in the formulas?) Next, the nitropropene or nitrostyrene (a nitrated benzene) must be reduced; this is related to hydrogenation. This is the most common method, it is fairly easy and inexpensive. However, I have included many other ways. Choose a formula that suits your needs.
use stopper when not addine sodium
PHENYLETHYLAMINE
50 g of benzylmethyl ketone, or analog, in 100 ccs absolute ethyl alcohol are placed in a liter round bottom flask having a long neck. The flask is fitted with a three way or claisen adapter (see Figure 20) which has a water jacket condenser fitted to the sloping limb and a stopper in the vertical limb. A bottle, contain- ing benzene and bright pieces of sodium (50 gms.) of such size
that they are easily dropped down the vertical limb, is prepared. The flask is heated on a water bath until the alcohol boils. The
pieces of sodium are then (one at a time) introduced through the vertical limb. The benzene adhering need not be removed from the sodium. The first pieces of sodium cause a vigorous reaction, but the alcohol is kept at a boil. When the reaction becomes sluggish a further 100 ccs of absolute alcohol is added and
brought to a boil, and the sodium is again added. This is continued until 500 ccs of alcohol and
water condenser (in reflux position) 3-way adapter
Amphetamines 41
40 gms of the sodium have been added altogether. Then the following test should be carried out to show that the reduction is complete.
Mescaline
l-(2,5-Dimethoxy-4-methyl-phenel)-2-aminopropane (DOMorSTP)
3,4-Methylenedioxyamphetanune
(MDA)
Molecular Structure of Some Amphetamines
A sample (2 ccs) is diluted with 2 ccs of coned hydrochloric acid. This mixture is boiled with Fehling's solution (1) prior to the addition of Fehling solution (2). If no reduction of the Fehling solution takes place the reduction of the oxime is finished.
When the reduction is complete and all of the sodium is dissolved, (Fehling's test can be bypassed by adding an approximate total of 45 to 50 gms. of sodium and dissolving completely; I do not recommend this as it may hurt the yield) the flask is cooled, and 200 ccs of water are added to decompose the ethoxide. The water condenser that had been rigged to reflux is now sloped to distill. Heating is continued on a water bath until distillation slackens. A further 200 ccs of water are added and the heating is now performed on a sand bath until all the alcohol has passed over and the distillation has reached a temp of 96°. The contents of the flask, consisting of a layer of amine and a layer of caustic soda, are cooled and poured into a separating funnel. A little ether is used to complete the transference of the amine. The total distillate, containing alcohol, water, and phenylethylamine, is made strongly acidic with HC1 acid (use a good PH indicator) and evaporated to a small bulk (a vacuum will speed this), after which the residual
aqueous solution of amine hydrochloride is added to the contents of the separating funnel, where
the excess of caustic soda liberates the base. After some time of standing, the lower layer of caustic is run off, the upper layer of amine is agitated with 20 ccs of 0.720 ether, and the final traces of caustic are separated. The product from the reduction of a number of 50 gm installments of benzyl methyl ketone can, with advantage, be united at this stage. The ethereal solution along
42 RECREATIONAL DRUGS
with the ethereal washings are dried over anhydrous sodium sulfate and distilled. At first, ether containing some amine passes over, this portion is kept separate for recovery as carbamate (it is alkaline to litmus). The temp of the distillate coming over then rises rapidly to 186°-187°, at which time the amine distills. The condenser which should be long, is only filled half way with water at this stage. The receiving flask should be fitted with a soda-lime filled drying tube, owing to the avidity of the amine for carbon dioxide. Yield: 90% theoretical (40 gm).
Phenylethylamine. Bp: 186°; easily soluble in organic solvents; moderately soluble in water;
strong base; absorbs carbon dioxide from air.