gabriel synthesis

[hsark]

SWIM has planned on doing this synthesis. But has seen very little info on it. Is this a waste of time? SWIM is doing many others. But is trying to save money and not use alot of solvents. The question is what are the yields. And would you do it againhaving other reactions avalible. sorry if this is upsetting. i just dont want to waste time.  

[PolytheneSam]

This patent has examples of the Gabriel synthesis in it.

Patent US5122535

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=/netahtml/srchnum.htm&r=1&f=G&l=50&s1=%275122535%27.WKU.&OS=PN/5122535&RS=PN/5122535

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[Rhodium]

Is it a fact that the Gabriel synthesis only works on primary halides? Does it work with tosylates?

This would be nice:

2,5-dimethoxyphenylmagnesium bromide + ethylene oxide -> 2,5-dimethoxyphenethylalcohol
2,5-dimethoxyphenethylalcohol + TsCl -> 2,5-dimethoxyphenethylalcohol tosylate
2,5-dimethoxyphenethylalcohol tosylate + K-phtalimide -> 2,5-dimethoxyphenethylphtalimide

The phtalimide is then halogenated and hydrolyzed to give 2C-B.

[PolytheneSam]

Here's something interesting.  I wonder if secondary alkyl halides have a chance with this.

http://www.cyf-kr.edu.pl/~pcbogdal/synlett/

Remarkable Fast Microwave-Assisted N-Alkylation of Phthalimide in Dry Media.
Synlett 37, 873-874 (1996)

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[hsark]

SWIM will look into these. And SWIM has to admithes been interested in the microwave tecnology. Only question is how size compatable are these reactions. SWIM has read on these and understands there fast and posible to do in hardly to no solvents. Has anybee actually tried this. Some advice would be appreciated. 

[raybeez]

Would you halogenate first, then hydrolyze? Or vise versa? Would elemental bromine do the trick? How would you seperate out the phtalimide afterwards? I've seen this phtalimide compound for sale many places, wouldn't mind looking into this.

>2,5-dimethoxyphenethylalcohol tosylate + K-phtalimide -> >2,5-dimethoxyphenethylphtalimide
>
>The phtalimide is then halogenated and hydrolyzed to give >2C-B.

[Rhodium]

I'd suggest halogenating (in the 4-position) first, as when the nitrogen is protected as the phtalimide, any side reactions originating from bromine/nitrogen interaction is eliminated. Elemental bromine is perfect for the halogenation.

Hydrolysis of the phtalimide moiety is carried out with either of 1) Hydrazine Hydrate, 2) Sodium borohydride, or 3) Ethanolamine. Separation of the amine from the byproducts is easily performed by the means of an acid/base extraction (in "1" above, phtalhydrazide is precipitated, and can easily be filtered off. Procedural details for 1-3 can be found using TFSE.

[Rhodium]

Experimental from JACS 75, 3004 (1953)

2,5-Dimethoxyphenethyl alcohol

n-Butyllithium was prepared from lithium (28g) and n-butyl chloride (180g) in dry ether (350 ml.). A solution of hydroquinone dimethyl ether (205g) in dry ether (776mL) was added in one portion and the solution allowed to stand for 15 hours. The reaction mixture was maintained at 0°C while ethylene oxide (130g) was passed in as a gas during 3 hours. After standing overnight the reaction mixture was poured into ice-water (2 liters). The organic layer was separated, dried and fractionated. There was obtained 182g (68%) of product, bp 130-142°C/0.7mmHg, n25D 1.5402.
This alcohol formed a p-nitrobenzoate which melted at 73-74°C. From the distillation residue (20g) 6g of a crystalline by-product, mp 134-135°C, was isolated.

2,5-Dimethoxyphenethyl Bromide

A solution of 2,5-Dimethoxyphenethyl alcohol (66g)  in benzene (65 ml) was stirred and cooled in an ice-bath while phosphorus tribromide (30g) in benzene (50 ml) was added dropwise. The solution was kept at 0-5°C for two hours and then at 60°C for four hours. Ice-water was added to the cool reaction mixture and the organic  layer was separated. The benzene solution of crude bromide was washed with ice-cold 5% sodium hydroxide solution, water and dilute hydrochloric acid. Acidification of the sodium hydroxide extract yielded about 20g of an oil containing phenolic by-products. The benzene solution was concentrated and the residual crude bromide distilled rather quickly at a low pressure and temperature. There was obtained 48g (54%) of 2,5-Dimethoxyphenethyl Bromide, bp 97-110°C/0.25mmHg, n24D 1.5542. There is decomposition of this bromide with distillation and in three separate attempts an analytically pure sample could not be prepared, some loss of hydrogen bromide took place even with evaporative distillation.