dioulasso
(Stranger)
12-31-03 01:12
No 479855
      Substituted Mandelic acids
(Rated as: excellent)
    

Substituted Mandelic acids


Uses of Mandelic acid and its phenyl substituted derivants:

1. Decomposition to the corresponding benzaldehydes w/ HNO3
as in: Post 391475 (pHarmacist: "One More piperonal patent, High-yielding", Novel Discourse)
This is a good alternative to aromatic formylations.

2. Reduction to the corresponding Phenylacetic acids
This can be done w/:
- HI/P as in     ../rhodium /phenylacetic.html (unsubstituted)
or: Patent US4590295 for 4-OH-PAA (from phenol in one pot)

For 4-OH-PAA: Patent US4198526
- Cr(III)Cl3 / Zn w/ 97% yield (!)cool
- H3PO2 (Hypophosphorous acid)
- Catalytic hydrogenation

3.  The synthesis of novell Pemoline analoges of phenetylamines, from mandelic acid esters.
According to ../rhodium /pemoline.html or Refs within.
(this is a wery INTERRESTING possibility!)laugh




Synthesis of substituted Mandelic acids:

I.) Reaction of substituted benzenes w/ Glyoxylic acid:


A. w/ aquaeous Glyoxilic acid in warious solvents. Substrate: 1,2-Methylenedioxybenzene (Benzodioxole),  in GAA, yield of 1,2-MD-mandelic acid is 95%
Patent EP1229031
Similarly in: Post 391475 (pHarmacist: "One More piperonal patent, High-yielding", Novel Discourse)

B. w/ aquaeous Glyoxilic acid in the presence of a tertiary amine and a trivalent metal catalyst.
Patent US5354897

C. w/ aquaeous Glyoxilic acid and aq. NaOH. Substrates: Phenols, yields are low (~30%)
Patent US4339602

D. w/ aquaeous Glyoxilic acid and Al2O3. Substrate: Catechol, yield:70%.
Patent US4165341
Post 225608 (foxy2: "Re: 4-Methylaminorex Synth w/o CNBr", Novel Discourse)

E. w/ Glyoxilic acid hydrate and 97% Formic acid (in: GAA). Substrate is 1,2,3,5-Tetramethyl benzene, yield: 71%.
Patent DE10029413

F. w/ Glyoxilic acid hydrate and 85% H3PO4. Substrate: 1,2-Methylenedioxybenzene, yield 76%
Patent US4190583
Post 225606 (foxy2: "Re: 4-Methylaminorex Synth w/o CNBr", Novel Discourse)

G. One more method w/ glyoxylic acid: Post 225604 (foxy2: "Re: 4-Methylaminorex Synth w/o CNBr", Novel Discourse)


I’ve found no reference for synthesis of alkoxy substituted mandelic acids. Deffinitely 2,5-Dimethoxymandelic a. would be the most interresting. Yields for both methylendioxybenzene and phenols are high (w/ aq. glyoxylic a., since thats the cheaper solution) thus succes on methoxy substituted compounds may be expected.

For synth of Glyoxilic acids see refs in: Post 427038 (foxy2: "Preparation of Glyoxylic acid", Novel Discourse)



II.) An alternative would be dichlorination of the corresponding acetophenones (lacrymatory), followed by alkaline hydrolysis. 
As in:Organic Syntheses, CV 3, 538 (http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0538)
(Dibromination may be an alternative.)


III.) Substituted mandelic acids can also prepared from subst. Benzenes by reactingh w/ ethyl oxomalonate in the presence of SnCl4, followed by alkaline hydrolysis.
Organic Syntheses, CV 3, 326 (http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0326)
(not too convenienttongue)




Looking forvard for your cooments and suggestions, especially concerning the pemoline analoge possibility and the methoxy issue!smile

" Unorthodox cooking, illicit cooking. A bit of real science, in fact. "
 
 
 
 
    roger2003
(Hive Bee)
12-31-03 11:16
No 479961
      Idea for Synthesis of (substituted) Mandelic acid     

Condensation of (substituted)Benzaldehyde and Nitromethan  --> 1-Phenyl-2-nitroethanol

Patent US2151517

Transformation of Primary Nitroalkanes

1-phenyl-2-nitroethanol --> Mandelic acid

Matt, C.; Wagner, A.; Mioskowski, C.
J. Org. Chem. 62, 234-235 (1997) (../rhodium/pdf /nitro2bromide2acid.pdf)
DOI:10.1021/jo962110n

.