89-56-5

Usage

Uses

Used in Pharmaceutical Industry:
5-Methylsalicylic acid is used as an intermediate in the synthesis of pharmaceutical compounds, due to its structural similarity to salicylic acid and its potential for chemical modification.
Used in Dye Manufacturing:
5-Methylsalicylic acid is used in the manufacturing of dyes, as it can be chemically modified to produce a range of colors and shades.
Used in Analytical Chemistry:
5-Methylsalicylic acid is used in the generation of o-sulfate conjugates in situ and their analysis by ultra-performance liquid chromatography-time-of-flight mass spectrometry, providing a valuable tool for the study of chemical reactions and compound characterization.
Toxicity:
The toxicity of 5-Methylsalicylic acid is similar to that of salicylic acid, which means it should be handled with care and used in appropriate concentrations to avoid adverse effects.

Preparation

5-Methylsalicylic acid can be prepared by hydroxylation of 3-methylbenzoic acid.

Purification Methods

Crystallise the acid from H2O. [Beilstein 10 H 227, 10 II 134, 10 III 516, 10 IV 610.]

InChI:InChI=1/C8H8O3/c1-5-2-3-7(9)6(4-5)8(10)11/h2-4,9H,1H3,(H,10,11)/p-1

Upstream product

• 56-23-5 tetrachloromethane 
• 106-44-5 p-cresol 
• 2941-78-8 2-Amino-5-methylbenzoic acid 
• 104-93-8 p-methylanizole 
• 79-37-8 oxalyl dichloride 
• 16108-51-3 2,6-dimethyl-chromen-4-one 
• 859085-54-4 2,6-dimethyl-3-propionyl-chromen-4-one 
• 623-11-0 1-methyl-4-nitrosobenzene 
• 88-61-9 2,4-dimethylbenzenesulfonic acid 
• 613-84-3 2-hydroxy-5-methylbenzaldehyde 
• 1470-57-1 2-hydroxy-5-methylbenzophenone 
• 4995-99-7 5-dimethylaminomethyl-2-hydroxy-benzoic acid 
• 141-52-6 sodium ethanolate 
• 80607-98-3 (Chlorformyl)ameisensaeure-p-tolylester 

Downstream Products

• 22717-57-3 methyl 6-hydroxy-m-toluate 
• 854645-32-2 ethyl 2-ethoxy-5-methylbenzoate 
• 854452-32-7 2-hydroxy-5-methyl-benzoic acid-(4-nitro-phenyl ester) 
• 952-47-6 2-hydroxy-5-methylazobenzene 
• 34265-58-2 ethyl 5-methylsalicylate 
• 10192-91-3 3-(chloromethyl)-5-methylsalicylic acid 
• 945981-89-5 2-formyl-6-hydroxy-3-methyl-benzoic acid 
• 106-44-5 p-cresol 
• 613-84-3 2-hydroxy-5-methylbenzaldehyde 
• 17746-75-7 3-bromo-5-methylsalicylic acid 
• 6049-93-0 2,3-dihydroxy-5-methylbenzoic acid 
• 59672-93-4 2-hydroxy-5-methyl-3-nitro-benzoic acid 
• 53938-41-3 2-hydroxy-5-methyl-benzoic acid anilide 
• 926214-03-1 3-chlorosulfonyl-2-hydroxy-5-methyl-benzoic acid 

Relevant academic research and scientific papers

Palladium-catalyzed ortho-C-H hydroxylation of benzoic acids

A simple Pd(OAc)2 catalyzed ortho-hydroxylation of benzoic acids using TBHP as the sole oxidant has been explored. This protocol features relatively broad substrate scope and operational simplicity. The compatibility of ortho-substituted substrates is an effective complement to the previous ortho-hydroxylation reaction.

Carboxylation of Phenols with CO2 at Atmospheric Pressure

A convenient and efficient method for the ortho-carboxylation of phenols under atmospheric CO2 pressure has been developed. This method provides an alternative to the previously reported Kolbe-Schmitt method, which requires very high pressures of CO2. The addition of a trisubstituted phenol has proved essential for the successful carboxylation of phenols with CO2 at standard atmospheric pressure, allowing the efficient preparation of a broad variety of salicylic acids.

A versatile approach for the synthesis of para -substituted arenes via palladium-catalyzed C-H functionalization and protodecarboxylation of benzoic acids

While a great number of ortho C-H functionalization reactions have been developed and several breakthroughs have been achieved in meta C-H activation, para C-H functionalization is still in its infancy stage. In this article, a versatile strategy for the synthesis of para-substituted arenes has been developed via a tandem process consisting of palladium-catalyzed C-H functionalization and subsequent copper-catalyzed protodecarboxylation of benzoic acids. Both electron-withdrawing and electron-donating functionalities can be introduced into the para positions of arenes bearing a variety of substituents.

Synthesis of cresotic acids by carboxylation of cresols with sodium ethyl carbonate

Carboxylation of o-cresol, m-cresol, and p-cresol with sodium ethyl carbonate (SEC) proceeds regioselectively with the formation of cresotic acids: 2-hydroxy-3-methylbenzoic acid, 2-hydroxy-4-methylbenzoic acid, and 2-hydroxy-5-methylbenzoic acid, respectively. Optimal conditions for conducting the process have been found to be as follows: the reactants ratio of [cresol]: [sodium ethyl carbonate] = (1.5–2): 1, T = 180–185°C, PCO2 = 10 atm, and t = 6–7 h. Simple and convenient methods for the synthesis of cresotic acids, which can be used for their industrial manufacturing, have been developed.

A concise synthetic route to the stereotetrad core of the briarane diterpenoids

A concise synthesis (under 10 steps) of the stereotetrad core of the briarane diterpenoids is reported. This approach harnesses the unique reactivity of salicylate ester derived 2,5-cyclohexadienones to quickly build complexity. In particular, a highly diastereoselective acetylide conjugate addition/β-ketoester alkylation sequence was used to set the relative configuration of the C1 (quaternary) and C10 (tertiary) vicinal stereocenters. The sterochemical outcome of the β-ketoester alkylation appears to be governed by torsional steering in the transition state.

General method for the synthesis of salicylic acids from phenols through palladium-catalyzed silanol-directed C-H carboxylation

A silanol-directed, palladium-catalyzed C-H carboxylation reaction of phenols to give salicylic acids has been developed. This method features high efficiency and selectivity, and excellent functional-group tolerance. The generality of this method was demonstrated by the carboxylation of estrone and by the synthesis of an unsymmetrically o,o′-disubstituted phenolic compound through two sequential C-H functionalization processes.

A Baker-Venkataraman retro-Claisen cascade delivers a novel alkyl migration process for the synthesis of amides

A simple extension of the carbamoyl Baker-Venkataraman rearrangement has been developed. If residual water in the reaction is not strictly excluded a Baker-Venkataraman retro-Claisen cascade takes place, giving amide products, in which an alkyl group apparently migrates between two functionalities of the substrate.

Regioselective ortho-carboxylation of phenols catalyzed by benzoic acid decarboxylases: A biocatalytic equivalent to the Kolbe-Schmitt reaction

The enzyme catalyzed carboxylation of electron-rich phenol derivatives employing recombinant benzoic acid decarboxylases at the expense of bicarbonate as CO2 source is reported. In contrast to the classic Kolbe-Schmitt reaction, the biocatalytic equivalent proceeded in a highly regioselective fashion exclusively at the ortho-position of the phenolic directing group in up to 80% conversion. Several enzymes were identified, which displayed a remarkably broad substrate scope encompassing alkyl, alkoxy, halo and amino- functionalities. Based on the crystal structure and molecular docking simulations, a mechanistic proposal for 2,6-dihydroxybenzoic acid decarboxylase is presented.

Sulfoximines: A reusable directing group for chemo-and regioselective ortho C-H oxidation of arenes

Sulfoximines direct: A new protocol for the chemo-and regioselective ortho C-H acetoxylation of arenes in N-benzoylated sulfoximines is reported. The sulfoximine directing group is easily detached from the C-H oxidation product through acid-promoted hydrolysis, isolated, and reused (see scheme). The meta-substituted phenols are synthesized following this strategy and the stereointegrity of the sulfoximine is preserved in this transformation. C(sp3)-H acetoxylation of the methyl group is also demonstrated.

PD(II)-CATALYZED HYDROXYLATION OF ARENES WITH O2 OR AIR

Pd (II) -catalyzed ortho-hydroxylat ion of variously substituted aromatic carboxylic acids under O2 or air is achieved under non-acidic conditions. Extensive labeling studies support a direct oxygenation of aryl C-H bonds with molecular oxygen.