Dear Bees!
Beelow you can see the synth of Modafinil from scratch – using essentially benzyl chloride and chloroacetic acid as starting ingredients. It was actually performed quite recently by our comrades Fomalhaut and Dionket, so you can ask any additional questions you want. Compliments are also much welcome .
The original can bee found at Post 430070 (missing)
(Fomalhaut: "Ñèíòåç Ìîäàôèíèëà îò À äî ß", Russian HyperLab).
1. Diphenylmethane.SOP (Syntheses of Organic Preparates) v.2, p. 233Into a 5-liter flask equipped w/a RC and a S-shaped tube connected to a addition funnel there’s placed 10g amalgamated Al grit (Note 1) and 2000g (2.3 L, 25.6moles) of benzene, which has been dehydrated by distillation (discarding the initial turbid portion). Benzene is heated to boiling, then heating removed and 500g of benzyl chloride are added at such rate that the soln continuously boils (Note 2). HCl is evolved. After the addition’s over (usually ~1hr) the mixtr is heated for 10-15mins or until HCl evolution stops. Upon cooling the solution is decanted from some tar (Note 3), washed w/5% NaOH and water. After drying w/CaCl2 benzene’s removed and the residue vac distilled , collecting: 125 C/10mmHg, main fraction 125-130 C/10mmHg, up till 150 C. Redistillation of 1st and 3rd fractions gives some additional qtties of the product which are pooled w/2nd fraction. The latter is frozen, the small qtty of unfrozen oil is decanted from the xtals.
The yield is 330-350 g (49.5-52.5%), mp 24-25 C
Notes:
1. Aluminium grit washed w/ether for defatting is stirred for several mins in 5% aq HgCl2, quickly washed w/water, then MeOH. Used immediately.
2. Occasionally the rxn takes some time to start. Initially one adds not more than 50-60g and the mixtr is heated until appearance of HCl indicates the beginning of the rxn. If one adds too much BzCl at once the contents of the rxn may bee thrown out onto the ceiling.
3. In this same flask containing aluminium and traces of tarry byproduct one may conduct several more syntheses, in which case no initial delay of the rxn is observed.
2. Diphenyl bromide.Of our own deviceInto the solution of DPM (84g, 0.5moles) in 300mls CCl4 bromine (25.8mls, 0.5moles) was added in small portions under UV lamp irradiation and temperature of ~60-70 C. The end of the addition funnel should bee immersed into the liquid, the deeper is the better. Each subsequent portion was added after discoloration of the previous one. To prevent loss of
bromine with HBr stream a RC with a double (?) was used. After the last portion’s color was gone, the mixtr was cooled, washed w/ice water, sat. cold aq NaHCO3, and once again icewater. Dried over CaCl2 and rotovapped off the solvt.
The remaining oil upon cooling solidified into a light-yellow xtalline mass. Yield of crude product – 105%, it was used w/out further purification. Should bee used as soon as possible (begins to smoke after 24hrs in a fridge).
3. Ethyl chloroacetateTitze & Eicher, p. 576A soln of 40g (887mmole, 50mls) EtOH, 47.3g (500mmole) chloroacetic acid and 2g tosic acid in 100mls CHCl3 is refluxed for 5hrs with a water-removing trap. The rxn mixtr is allowed to cool, washed w/water, sat. NaHCO3, brine and dried over Na2SO4. The solvt is stripped off, the residue vac distilled – yield 47.3g (72%), èç 73-74 Ñ/50mmHg
4. ChloroacetamideSOP v.1, p.476Into a 2L RBF equipped w/a mech stirrer immersed in a icebath there’s placed 215g (1.75moles) ethyl chloroacetate. At 0-5 Ñ and energetic stirring there’s added 200g of well chilled aq. NH3 (d=0.9). The mixtr is stirred in the cold for 15mins, then another 200mls aq. NH3 is added and stirring cont’d for 15 more minutes. The mixtr is allowed to stand for 30mins, the precipitated product is filtered and washed twice with 2x100-120mls water. The yield of air-dried product is 128-138g (78-84%), mp 118-199 C, traces of moisture depress mp very significantly.
5. 2-Benzhydrylsulfanylacetamide.130g (~0,5moles) of crude diphenylmethylbromide was boiled in 500mls water with 0,5moles thiourea and further treated with alkali (1.25moles NaOH) and chloroacetamide (0,5moles) as described in
Post 429898
(Antoncho: "The Making of Modafinil", Novel Discourse). The yield of product was 80g (62% counting on starting diphenylmethane).
There was one difference though. Addition of DPM-bromide into the thiourea soln was carried not in one portion, but rather by dissolving the stuff in 60-70mls IPA and dripping it into the boiling mixtr thru an addition funnel. Upon which the rxn mixture assumed bright blue color
and Dionket had an hysterical seizure
fearing that all was lost. Happily, that wasn’t the case. After 10min reflux almost all DPM-Br dissolved, after addition of alkali color disappeared and an oil precipitated.
6. Modafinil80g of 2-benzhydrylsulfanylacetamide in 400mls GAA was oxidized with 60mls (approx. 2x xcess) 30% hydrogene peroxide at 10-15 C. Addition of H2O2 causes significant warming, good cooling was required. Better not heat it above 15 C – it will overoxidize to the sulfone. Reaction time is ~20hrs. After dilution w/water to 1,5L and filtering there was obtained 76g (89%) of crude Modafinil. Rextallization from MeOH (~1 liter) gave 36g (43%) of product – since we are greedy, obviously we’re going to evaporate the mother liquor to get out the rest
, but this haven’t been done as of now (the lab’s closed – it’s May Holidays in Russia).
As far as the subjective effects are concerned, I was going to translate Dionket’s comments but found two excellent threads on the Hive : Post 253501 (missing)
(PapaSmerck: "Modafinil Experiences?", General Discourse) & Post 385999 (missing)
(methadist: "Provigil", General Discourse) in which this subject is covered completely. Sounds similar to our comrades’ experience in every respect (xcept they used dosages of 200mgs).
It appears to bee an ideal upper without noticeable side-effects and addictive properties. Personally I'd give very much for an opportunity to have some or make some In Russia, they don't even sell it on prescription
Antoncho