Reduction of salicylic acids to 2-methylphenols

Lego · Tue Aug 09, 2005 1:15 am

An easy two-step reductionof salicylic acids and alcohols to 2-methylphenols
Francesco Mazzini, Piero Salvadori
Synthesis, 2005, DOI:10.1055/s-2005-872072
http://dx.doi.org/10.1055/s-2005-872072
http://rapidshare.de/files/3784676/s-2005-872072.pdf.html

Synthesis of o-Cresol; Typical Procedure
To a solution of salicylic acid (1.12 g, 8 mmol) and Et₃ N [2.9 mL, 20.8 mmol, 2.6 equiv (1.1 equiv in the reduction of salicylic alcohols)] in THF (50 mL) at 0 °C was added ClCO₂ Et [2 mL, 20.8 mmol, 2.6 equiv (1.1 equiv in the reduction of salicylic alcohols)], and the mixture was stirred for 3 h at 0 °C. The resulting white precipitate was filtered off and washed with THF (15 mL). The combined filtrates were concentrated to small volume, re-diluted with THF (15 mL) and carefully added to a solution of NaBH₄ (2.43 g, 64 mmol, 8 equiv) in H₂ O (15 mL) at 0 °C. After 3 h at 0 °C, the temperature of the white suspension was allowed to rise to r.t. and it was stirred for an additional hour. The mixture was neutralized with 1 M HCl and THF was evaporated. The aqueous layer was extracted with EtOAc and the combined organic extracts were subsequently washed to neutrality with water and dried over Na₂ SO₄ . Purification by column chromatography (hexane–EtOAc, 3:1) gave o-cresol (800 mg, 92% yield).

So this could turn salicylic acid into a valuable precursor for DOM.
Oxidation of salicylic acid (2-hydroxybenzoic cid) to 2,5-dimethoxybenzoic acid, reduction, methylation and formylation and there is 2,5-dimethoxy-4-methylbenzaldehyde Smile

Oxidation of salicylic acid to 2,5-dimethoxybenzoic acid:
Posted by Lego in the old Hive board, very oldschool Wink

but it works...

2,5-Dihydroxysalicyl alcohol from hydroquinone:
https://www.synthetikal.com/hiveboard/chemistrydiscourse/000490200.html

lemuralia · Tue Aug 09, 2005 2:30 am

Cool post,Thanks! Very Happy

java · Consumer

Good find Lego...it stands to reason that if NaBH4 will reduce COOH in phenylalanine , it will reduce in this case the function on benzylic type carboxylic acids* and since NaBH4 sill also reduce benzylic type alcohols** with a little help from Al( III)Cl, then it's reasonable to see this catalyst NaBH4 being used on this reaction...................I was hoping it would also work in non benzylic aromatic primary alcohols also...................java

*-Direct Link URL: http://home.ripway.com/2005-1/247174/TransitionMetalCompoundMediatedReductionof-AminoAcids.pdf
Alternate URL: http://host.picturewizard.com/2005-1/247174/TransitionMetalCompoundMediatedReductionof-AminoAcids.pdf

**-Direct Link URL: http://home.ripway.com/2004-11/211899/nabh4+al(iii)clreduction.pdf
Alternate URL: http://host.picturewizard.com/2004-11/211899/nabh4+al(iii)clreduction.pdf

lemuralia · Mon Aug 15, 2005 7:09 am

when reducing the COOH to the alcohol is THF really required? Can another solvent be used?

java · Consumer

If you read the transitional metal compound, you will see they use water as the solvent......much better for me ...........java