another possiblity is a post ullman made on SM
Ullmann
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New OTC methylating agent - Methyl Ethane Sulfonate (MES)
(A.) Methyl Methane Sulfonate (MMS) generation from Mesyl Chloride and Methylation of Salicylaldehyde therewith followed by (B.) Methyl Ethane Sulfonate (MES) generation from the Ethane Sulfonyl Chloride prepared from the in situ Chlorination of the Bunte salt from Sodium Thiosulfate and Ethyl Bromide. A cheap and easy way to methylating agent for the amator chemist.
A. Preparation of MethylMethaneSulfonate (MMS) from commercially avaiable mesyl chloride. Its use for methylating salicylaldehyde in a one pot reaction. A generation and in situ utilisation of a very toxic methylating agent avoiding the trouble and danger of stocking it.
In a 500 ml three necked RBF with a N2 inlett, a dropping funnel, a condensator with a silicagel tube. To a methanolic solution of 150 mmol methanesulfonyl chloride (MM 115, 17.3 g, d1.48, 11.7 ml) in 100 ml of cold dry MeOH (ice bath/salt), there is added during 15 minutes dropwise with cooling 150 mmol of sodium methoxyde 3M solution in MeOH (50 ml, 150 mmol). NaCl precipitate. After the addition is done the mixture is let reach RT over 15 minutes. There is thus obtained 150 ml of 1M solution of MMS in MeOH (+salt). It is used as such for the next reaction.
To the above prepared 1M solution of MMS in MeOH there is dissolved 12.2 g (MM 122, 100 mmol) salicylaldehyde. There is then added in one portion anhydrous Na2CO3 (2 eq, 200 mmol, MM 106, 21.2g). The N2 inlet is taken off and the mixture is then refluxed for the night. The next morning the conversion was 73% (HPLC vs references), it was homogeneous on chromatography.
Another run was attempted using Na2CO3 as a base for the generation of MMS:
In a 500 ml three necked RBF with a N2 inlett, a dropping funnel, a condensator with a silicagel tube. To a suspension of anhydrous Na2CO3 (300 mmol, MM 106, 32 g) in MeOH (150 ml) there is added via seringue dropwise and with cooling 150 mmol methanesulfonyl chloride (MM 115, 17.3 g, d1.48, 11.7 ml). An exothermic reaction occur. After the addition is done the mixture is let reach RT over 30 minutes. It is used as such for the next reaction. Addition of 100 mmol salicylaldehyde and reflux overnight gave a 70% conversion to o-anisaldehyde (vs references again).
Now having shown the possibility of generating the carcinogenic methylating agent and using it in situ let it become OTC by making our own Ethane Sulfonyl Chloride...
B. Methyl EthaneSulfonate (MES) generation from the Ethane Sulfonyl Chloride prepared from the in situ Chlorination of the Bunte salt from Sodium Thiosulfate and Ethyl Bromide.
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The Interaction of Chlorine with Different Types of Organic Sulfur Compounds
Ref: JACS 60 1486
In some runs the sodium alkylthiosulfate was formed
by mixing the alkyl halide or sulfate (0.1 mole) with an
equivalent amount of 20% sodium thiosulfate solution and
50-75 cc. of acetone. When the formation of a homogeneous
solution indicated complete reaction the acetone was
removed with steam and the solution cooled and chlorinated
as usual. In this manner a 55% yield of ethylsulfonyl
chloride was obtained. An attempt to form sodium
cyclohexyl thiosulfate using cyclohexyl chloride was
unsuccessful.
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In a one liter RBF:
EtBr : 0.5 mole MW 109 d 1.46 --> 55 g = 38 ml (I add 40ml)
Sodium thiosulfate.5 H20 : 0.5 mole MW 248 --> 124 g dissolved in 400 ml H20
Acetone 250 ml
After one day of stirring a clear homogeneous solution is obtained. Acetone is then evaporated. According to US2293971 there is added 200 ml of GAA to the 300 ml of solution obtained. Meanwhile in another 1L RBF there is placed 300 g sodium dichloroisocyanurate (MW 220, 85%, 1160 mmole, 55% chlorine -> 140 g active chlorine (2 moles)) covered with a small amount of water. With the help of a teflon tubing through septums bridging the two 1L RBF and going into the solution with the bunte salt chlorine is generated for two hours and passed in by dropping at 0-15°C 250 ml of 32% HCl (2.5 mole) on the DCCA. Be cautious of back pressure jump and frothing! Near the end of generation of the chlorine the solution with bunte salt took a permanent yellow-green tinge. It means excess chlorine was present. After ten minutes it was still yellow and workup was started. The solution is pourred in one liter of water which precipitated 30 g of ethane sulfonyl chloride. Four extractions with 4x50 ml CH2Cl2 were done and all fractions are combined then washed once with sulfite and two times with water. The CH2Cl2 evaporated in vacuo and the yellow and fluid residue is weighted : 62 g is obtained MW 128 -> 468 mmol (94%).
The generated ethanesulfonyl chloride is then used for methylation by decomposing it in MeOH with a carbonate.
Although this reaction work as described some tuning must be done in regard to the lot of salts generated and consequent trouble in stirring the reaction. For instance if syringaldehyde is used as substrate instead of salicylaldehyde the sodium salt will be unstirrable because of too much salt/insolubility of Na+/-syringaldehyde. Use of K2CO3 or KOH in MeOH or acetone or DMF will then probably be preferable if ever the K salt of say for instance syringaldehyde is more soluble in MeOH than the Na salt. At worst a cautious filtration or decantation of the methanolic MES solution from the generated NaCl and NaHCO3 may be useful or necessary.
Enjoy!
Kind Regards,
Dr Ullmann
[Edited on by Ullmann]
CV5P1085.pdf