Substituted Mandelic acids

[dioulasso]

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    

https://www.thevespiary.org/rhodium/Rhodium/chemistry/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 (!)
-   H3PO2 (Hypophosphorous acid)
-   Catalytic hydrogenation

3.  The synthesis of novell Pemoline analoges of phenetylamines, from mandelic acid esters.
According to

https://www.thevespiary.org/rhodium/Rhodium/chemistry/pemoline.html

or Refs within.
(this is a wery INTERRESTING possibility!)



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 convenient )



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

[roger2003]

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) (

https://www.thevespiary.org/rhodium/Rhodium/pdf/nitro2bromide2acid.pdf

)
DOI:10.1021/jo962110n