An excerpt from an old Uemura Notebook.
I. 345-Trimethoxyphenyldiazomethylketone.
18,9grms 3,4,5 Trimethoxybenzoylchloride [1] (approx 0,086 mol) are dissolved in dry ether to give a saturated solution at 0-5 Degc. Under cooling at 0 DegC an etherical solution of a slight molar excess of diazomethan (dryed with KOH) [2] is added during 1 hour. The mixture is kept at -15DegC for 24 hours.
The diazoketone is filtered. Yield 14,5 grms (about 72%). Fractional removal of the ether of the filtrate gives another portion of 1.5grms of diazoketone. mp 102-103DegC. Total yield 78%. It can be re-xtalised from Acetone-Ether, mp is increased to 103-104 DegC.
Complete evap of the ether gives 3,2 grms of the side product, the diazochloroketone.
II: 345-Trimethoxyphenylacetamide (Ardnt-Eisner Reaction)
5grms of the above diazoketone are dissolved in 12ml dioxane which had been dried over sodium. Then 7ml of a 10% solution of AgNO3 and 70ml concentated NH3 (aq) are added. Then the mix is heated for 2 hous on a waterbath and NH3 is bubbled thru. Following a three hours reflux, hot filtration. At 50Degc the mix is evaporated to dryness. The residue is solved in the minimul amount of water. Upon cooling 3,2 grms of pure acideamide (67%) xtalises. A further amount of 1 grm can be extracted from the mother liquor after evap to dryness and extracting with benzene. mp 124-125DegC.
III. 345-Trimethoxyphenylethylamin
Reduction of the phenylacetamide with LAH in a soxlhet apparatus.
Uemura recommends to test the activitiy of the LAH, otherwise you may loose all of your precious product prepared above [3]
Theory: R = 3,4,5-trimethoxyphenyl-
I. R-COCl + CH2N2 -> HCl + R-C(O)-CH(-)N2(+)
II. R-C(O)-CH(-)N2(+) + Ag --> R-C(O)-C-H + N2 <--> O=C=CH-R (+NH3) --> R-CH2-CONH2
In total:
R-COCl --> .... --> R-CH2-CONH2
References: Hel. Chem. Acta 1952, p 1577
[1] Prepared from 3,4,5 Trimethoxybezoeacide and PCl3.
[2] CH2N2 eg from nitrosomethylurea
[3] That was the end of his carrier at those times....
