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Mannich route to 2-CH
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Place 124 g of p-methoxyphenol in a round-bottomed flask (placed in cold
water-bath) with addition funnel and stirrer. Add 173 ml 29% aqueous
dimethylamine (methoxyphenol completely dissolved). Drop by drop add 110 ml
of 27% formaline, the temp was maintaned near 25-30 during the addition.
The reaction mixture stirred another hour, and all volatiles completely
removed in vacuo, . To dark oily residue was added 600 ml of acetonitrile
(IPA may be used) containing 120 ml of methyl iodide. Exotermic reaction
appears; use reflux condensor for minimum loss of CH3I. Best temp range for
quaternisation 30-40C; below 15C reaction almost stops. Keep the reaction
mixture in water bath (30-50C) for 3 hrs, then leave in cold place
overnight. Deposited slighly yellow crystals filtered off, mother liquor
reduced twice in volume under vacuo, and cooled once more. After filtering
of second crop, the yield of quaternary salt is near 200 g or 62% theory.

Place 200 ml of 40% NaCN soln (d=1.4) in flask, (equipped with addition
funnel, mechanic stirrer and 50-cm glass tube as air condenser) and add 300
ml of DMF. Dissolve 200 g (0.62 mole) of quat. salt in 200 ml of DMF, and
place this soln in addition funnel. Heat about 80-90C and at this temp drop
by drop add soln of quat. salt to DMF suspension of cyanide (last not
completely dissolved). Do it under good fume hood during 30-40 min. Strong
evolution of trimethylamine observed. When addition complete, stir another
1 hour at 80-90C. After cooling homogeneous dark reaction mixture poured in
2 l of water and extract 4-5x150 ml portions of chloroform or methylene
chloride. Pooled extract was washed once with brine and quickly dried by
shaken with anhydrous Na2SO4. Chloroform was distilled off under water pump
vacuo; and then was distilled off DMF, taken by chloroform extraction.
Resudue crystalizes on chilling, 62-65 g. of 2-hydroxy-4-methoxybenzyl-
cyanide (62%). Used as such for the next step.

65 g (0.386 mole) of previously obtained benzylcyanide placed in RB flask
(addition funnel, stirrer, reflux condenser), 400 ml of acetone added, and
then added 100 g of finely powdered K2CO3. As PTC catalyst added 10 ml
PEG-400 (polyethyleneglycol). To this mixture added 50 ml of methyl iodide
drop by drop during 1 hr. and mixture stirred 14 hrs at 55-60C. Initial
dark color changes to light yellow; after cooling solid salts was filtered
off, washed by fresh acetone, to acetone 50 ccm water added and solvent
removed in vacuo. Resudue was extracted with CH2Cl2, extract dryed with
Na2SO4, and solvent removed, - 62 g of 2,5-diMeO-benzylcyanide, 91% yield.

Place 24 g (0.136 m)of 2,5-di-MeO-benzylcyanide in flask, add 300 ccm of
96% ethanol, and then 15 g of anhydr. NiCl2 (or 20 g hydrate). Under
magnetic stirring add 38 g (1 mol) of NaBH4 in small portions durind 30-40
min. Immediately black color appears. Temp. during the addition rose to
40-50C, and evolution of H2 observed. When addition of borohydride
complete, stir another 3 hrs at 40-50C, and after cooling 200 ml of 3N HCl
added into the reaction mixture and that stirred till the black precipitate
dissolved. After removal of ethanol under vacuo and extracting of unreacted
nitrile with ether or hexane, the aqueous layer made alkaline with conc
ammonia soln and then extracted with ether 3-x times. Combined extract
washed with brine, dried over MgSO4 and evaporated. Obtained oil (2-CH) 
(19g, 73% yield) used as such for bromination

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Reduction of 3,4,5-Trimethoxybenzylcyanide

Placed 11.6 g (0.056 m)of 3,4,5-tri-MeO-benzylcyanide in flask, added 300 ml of
methanol, and then 20 g of  NiCl2  hydrate. Under magnetic stirring added 19g
(0.5 mol) of NaBH4 in small portions over 30 min. Immediately black color
appeared. Temp. during the addition rose to 40-50C, and evolution of H2
observed. Flask was cooled with an ice/water bath to prevent violent boiling.
When addition of borohydride was complete ice bath was removed and flask stirred
for 3 hours at room temperature, after cooling 200 ml of 3N HCl added to the
reaction mixture and the black solids filtered [recycling the nickle boride].
After removal of methanol at the rotovap unreacted nitrile [~1gm] was extracted
with DCM, the aqueous layer made alkaline with conc. ammonia soln [turns deep
blue upon addition of ammonia] and then extracted with DCM 3x100 ml. Combined
extracts were washed with brine, dried over MgSO4 and evaporated. Obtained an
oil (8.2g, 71% yield) which was converted to the HCl salt by dissolving in 20 ml
IPA, acidified w/110 drops conc. HCl [to pH4] and precipitated by the addition
of 100 ml diethyl ether to yield 8.5 gm snow white needles [62% yield overall].

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