[75-75-2] · CH4O3S · Methanesulfonic Acid · (MW 96.12)
(cyclocondensation reagent; precursor for methanesulfonyl chloride and anhydride; catalyst for polymerization, alkylation, and esterification reactions)
Alternate Name: MsOH.
Physical Data: mp 20 °C; bp 167 °C/10 mmHg, 122 °C/1 mmHg; d 1.481 g cm-3; n
Solubility: sol water, ethanol, ether; insol hexane; very sparingly sol benzene, toluene.
Form Supplied in: technical quality is 95% pure containing 2% water.
Analysis of Reagent Purity: 17O NMR.1
Preparative Method: by oxidation of Dimethyl Sulfide with Dimethyl Sulfoxide in the presence of water and a catalytic amount of Hydrogen Bromide.17
Purification: stir with P2O5 (20 g for 500 mL of the acid) at 100 °C for 0.5 h and then distill under vacuum.
Handling, Storage, and Precautions: irritant and highly corrosive liquid; should be stored in glass containers. Use in a fume hood.
MsOH is a weaker acid than Trifluoromethanesulfonic Acid and hence only few reports exist on the use of pure MsOH in cyclocondensation reactions.2 MsOH in dichloromethane effects a symmetry allowed cyclization of the precursor diene to afford 1,2,3,4-tetramethyl-5-(trifluoromethyl)cyclopentadiene, which is used as a ligand in organometallic chemistry (eq 1).3
A 1:10 solution by weight of Phosphorus(V) Oxide in MsOH4 is a convenient alternative to Polyphosphoric Acid for cyclization reactions. For example, the classical preparation of cyclopentenones via intramolecular acylation of alkenoic acids or their lactones (eq 2) and Beckmann rearrangement using polyphosphoric acid (eq 3) give comparable yields when performed with MsOH/P2O5.4
MsOH in conjunction with P2O5 has been used in the rearrangement of 2-vinylcyclobutanones to spiro and fused cyclopentenones (eqs 4 and 5).5
3-Unsubstituted indoles are formed regioselectively by treatment of precursor hydrazones with MsOH/P2O5.6 In the example given in eq 6,6 only 2-3% of the undesired 3-isomer is formed. Because decomposition sometimes occurs, it is advisable to dilute the reagent with a suitable polar, nonbasic solvent like sulfolane or dichloromethane.
MsOH itself is a better cyclizing agent than an admixture with P2O5 for the cyclization of 3-arylpropanoic and 4-arylbutanoic acids to 1-indanones (eq 7) and 1-tetralones (eq 8).7
Cyclization with neat MsOH is also observed in the formation of cyclopentenones from 2-vinylcyclobutanones (eq 9).5
MsOH has also been employed successfully in cyclocondensation reactions in the field of heterocycles (eq 10).8,18 Thus the hexahydroimidazo[1,2-a]pyrimidine-5,7-dione shown in eq 10 gives the corresponding cyclized product in 81% yield.8
MsOH is superior to Sulfuric Acid as the solvent and catalyst for the conversion of benzoic acid to Perbenzoic Acid (eq 11).9
MsOH in the presence of methionine is the reagent of choice and an excellent substitute for Boron Tribromide for O-demethylation of opioid derivatives (eq 12).10 Among the other reagents tested, only TfOH is as effective as MsOH/methionine.
Schmidt rearrangement of optically active cyclic b-keto esters with retention of configuration is effectively carried out with MsOH in the presence of Sodium Azide (eq 13).11
Attempted acid-induced cyclization with MsOH of an intermediate diazo ketone involved in the synthesis of tricyclo[5.2.1.04,10]decane-2,5,8-trione affords the corresponding methylsulfonyloxy derivative via the protonated diazonium salt (eq 14).12
MsOH is a useful reagent for the condensation of 2-(hydroxymethylene)cyclohexanone with sulfonamides in the presence of molecular sieves to afford products in the cis-u diastereoisomeric forms and with >90% stereoselectivity (eq 15).13
The reaction of trimethylphosphine-borane with MsOH in dichloromethane gives the methanesulfonate derivative of the borane (eq 16).14 This compound can be condensed with diphenylphosphine-borane in the presence of Sodium Hydride to give the corresponding dimer. By repeating the sequences of mesylation and condensation, a tetramer containing a linear P-B bond has been synthesized.14
MsOH has also been used to deblock the benzyl protecting group15 and to carry out the acidic hydrolysis of esters.16
Phosphorus(V) Oxide-Methanesulfonic Acid;
Lakshminarayanapuram R. Subramanian & Michael Hanack
Universität Tübingen, Germany
Antonio García Martínez
Universidad Complutense de Madrid, Spain