Substituted Mandelic acidsUses of Mandelic acid and its phenyl substituted derivants:1. Decomposition to the corresponding benzaldehydes w/ HNO3as 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 acidsThis 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!