Hi everyone,
D was very excited to see Bandils' success with the synthesis of 4-MAR with the use of KOCN. D is deeply intrigued by this substance and would like to dream up its existence and was wondering if someone could possibly offer some advice about the production of the precursor, dl-PPA. Though it may seem more appropriate to derive PPA from the reaction of nitroethane and benzaldehyde, it would be nice to derive dl-PPA through the Akabori rxn of benzaldehyde and dl-alanine for practical reasons. If this direction seems futile, please by all means speak your mind and D will get off the train here as he doesn’t have any experience with this reaction.
IOC performed a run by combining 100g BnZ and 40g l-alanine, heating the mixture to 140 (until fizzing stops),extracted the post reaction with H2O, concentrated, then cleaned up the crude product (how it was cleaned wasn’t specfied). In this case there was 15 % yield - which was low but for D, 15% yield would suffice if properly purified. Given PPA is produced, D thinks the next issue is to determine the nature of side products and how to separate them from the target especially when they are likely to be in large quantities from a low yielding reaction. According to Takagi et al (1): When BzH and DL-alanine are heated directly; PhCH2NH2, PhCH(OH)CHPhNH2 (2 dl-compds.), AcH, and CO2 are formed.
D searched for the physical data on PPA and these side products. These (incomplete) data are indicated below (2).
Proposed cleanup (a work in progress): After extracting the post reaction with water, it would be expected that at least benzylamine (PhCH2NH2), being water soluble, would travel along with the PPA. Since the bp of benzylamine, 182 - 185 deg C (760mmHg), is about 80 degrees higher than PPA base then the mixture could be distilled to collect a fraction at 100-105 deg C containing PPA base and water. D is unsure about how to subsequently separate the PPA base from water given their bp’s are so close. D had difficulty finding the bp or solublity data for 2-amino-1,2-diphenylethanol (PhCH(OH)CHPhNH2) so D is still unsure about how to predict its removal.
My questions are:
1) It is assumed that the post reaction will be basic and therefore PPA in its base form, is this correct?
2) Could one separate PPA base from water by acidifying it (making PPA-HCL which has a higher bp than water) and concentrating the mixture?
3) Does anyone know where to find the solubility and bp data for the 2-amino-1,2-diphenylethanol contaminant?
4) Can benzylamine be removed from the reaction mixture as proposed above?
5) What does "AcH" abbreviate?
Any input, directions and comments would be much appreciated!
Take care
DrIvEn
References and Data:
(1) Reaction between aromatic aldehydes and a-amino acids. I. New facts on the Akabori reaction. Takagi, Eiichi. J. Pharm. Soc. Japan (1951), 71 648-51.
(2) Physical Data of Various Chemicals Produced by the Akabori Reaction of Benzaldehyde and dl-alanine
Phenylpropanolamine (racemic mix of d- and l-norephedrine)
Base Bp: 101-101.5°
HCl Bp : 190-194°
HCl (+)-form Bp : 171-172°
PhCH2NH2 is benzylamine:
Physical State:
Liquid Appearance: clear colorless to slightly yellow
Odor: ammonia-like
pH: Not available.
Vapor Pressure: 0.6 mbar @ 20 deg C
Viscosity: mPas 20 deg C
Boiling Point: 182 - 185 deg C @ 760.00mm Hg
Freezing/Melting Point: 10 deg C
Solubility in water: > 500 G/L (20°C) IN WATER
Specific Gravity/Density: .9810g/cm3
d,l-PhCH(OH)CHPhNH2 is 2-amino-1,2-diphenylethanol:
This compound has several racemic forms, (1R,2R)(1S,2R)(1RS,2RS),(1RS,2SR)
For example: (1R,2R)-(+)-2-Amino-1,2-diphenylethanol:
Product Number 523704 CAS Number 88082660 Formula C14H15NO Formula Weight 213.3 APPEARANCE WHITE POWDER MELTING POINT 143.8-146.8 DEGREES CELSIUS INFRARED SPECTRUM CONFORMS TO STRUCTURE. PROTON NMR SPECTRUM CONFORMS TO STRUCUTRE. TITRATION 99.1 % (WITH HCLO4) OPTICAL ROTATION +7.5 DEGREES (C=0.6198%, ETOH)