Methyl sulfate

Reactions of the Hydroxyl Group. The hydroxyl proton of hydroxybenzaldehydes is acidic and reacts with alkahes to form salts. The lithium, sodium, potassium, and copper salts of sahcylaldehyde exist as chelates. The cobalt salt is the most simple oxygen-carrying synthetic chelate compound (33). The stabiUty constants of numerous sahcylaldehyde—metal ion coordination compounds have been measured (34). Both sahcylaldehyde and 4-hydroxybenzaldehyde are readily converted to the corresponding anisaldehyde by reaction with a methyl hahde, methyl sulfate (35—37), or methyl carbonate (38). The reaction shown produces -anisaldehyde [123-11-5] in 93.3% yield. Other ethers can also be made by the use of the appropriate reagent. 

Methylation. Methylating agents such as methyl sulfate and methyl iodide react with coumarin in the presence of sodium hydride to give methyl 2-methoxycinnamate [15854-58-7] (29). 

Cinnolin-3(2//)-one (7) is methylated with diazomethane or methyl sulfate to give 2-methylcinnolin-3(2H)-one. In a similar manner, benzylation with benzyl chloride, cyanoethylation with acrylonitrile in the presence of benzyltrimethylammonium hydroxide and glucosidation with tetra-O-acetyl-a-o-glucopyranosyl bromide in the presence of a base affords the corresponding 2-substituted cinnolin-3(2//)-ones. However, glucosidation of the silver salt of cinnolin-3(2//)-one produces the corresponding O-substituted compound. 

Methoxymathyl methyl sulfate 3 as an electrophilic reagent (or melhoxymethylalion of alkenes... 

Methoxymethyl methyl sulfate (3). To a stirred solutran of dimelhoxy methane 1 (6 08 g, 80 mmol) in CH2CI2 at 60°C was added freshly distilled SO3 2 (6 40 g, 80 mmol) to give a solutran of 3... 

Me2S04, 2 N NaOH, MeOH, H2O, reflux, 30 min, 85% yield.In this case the hemiacetal of phthaldehyde is alkylated with methyl sulfate this use is probably restricted to cases that are stable to the strongly basic conditions. 

To a cold solution of 80 g. (2 moles) of sodium hydroxide in 500 cc. of water in a i-l. flask is added 50 g. (0.266 mole) of gallic acid. The flask is immediately tightly stoppered (Note i), and the mixture shaken occasionally until all the acid has dissolved 89 g. (67 cc.) of methyl sulfate (0.71 mole) is then added (Note 2) and the flask is shaken for twenty minutes, being cooled by means of cold water in order that the temperature does not rise above 30-35°. Occasionally the stopper is raised to release any pressure. A second portion of 89 g. of methyl sulfate is then added and shaking continued for ten minutes longer. During this second addition the temperature may rise to 40-45°. 

The toxic nature of methyl sulfate vapor must always be borne in mind. 

Trimethylgallic acid is most conveniently prepared by methylating gallic acid with methyl sulfate. It has also been obtained... 

C. Pyocyanine alkylation). A solution of 2 g. (0.011 mole) of a-hydroxyphenazine in 13.4 g. (10 ml., 0.1 mole) of methyl sulfate (Note 10) is placed in a 250-ml. Erlenmeyer flask fitted with a calcium chloride drying tube and heated at 100° (oil bath) for 10 minutes. The solution is allowed to cool to room temperature, and about 7.5 ml. of dry ether is added. The dark brown solid is filtered on a 7-cm. Eiichner funnel and washed with about ISO ml. of dry ether in several portions (Note 11). 

The methyl sulfate should be frcshlj distilled under reduced pressure. 

W-Metbylpbenazonium metbosulfate see 5-methylphenazinium methyl sulfate on p. 547 in Chapter 6. 

Neostigmine methyl sulfate [51-60-5] M 334.4, m 142-145 . Crystd from EtOH. (Highly TOXIC.]... 

Methylphenazinium methyl sulfate [299-11-6] M 306.3, m 155-157 (198°dec by rapid heating). It forms yellow prisms from EtOH (charcoal). Solubility in H2O at 20° is 10%. In the presence of aqueous KI it forms a semiquinone which crystallises as blue leaflets from EtOH. [Wieland and Roseen Chem Ber 48 1117 1913, Voriskova Collect Czech Chem Commun 12 607 1947, Biilow Chem Ber 57 1431 1924.]... 

Occasionally we have found iron contaminants in aromatic steroids that have not been adequately purified. The methylation of a phenolic steroid with methyl sulfate and alkali is often carried out just prior to a Birch reduction and iron in the tap water precipitates with the steroid during the... 

Benzyloxycarbonyloxy)phenyl]dimethylsulfonium methyl sulfate, NaOH, H20,51-95% yield. " This is a water-soluble reagent for benzyloxy carbamate formation. Analogous reagents for the introduction of BOC and Fmoc were also prepared and give the respective derivatives in similar high yields. 

The nitration of l,2,5-selenadiazolo[3,4-/] quinoline 77 with benzoyl nitrate affords the 8-nitro derivative 78, whereas methylation with methyl iodide or methyl sulfate afforded the corresponding 6-pyridinium methiodide 79 or methosulfate 80, respectively (Scheme 29). The pyridinium salt 80 was submitted to oxidation with potassium hexacyanoferrate and provided 7-oxo-6,7-dihydro derivative 81 or, by reaction of pyridinium salt 79 with phenylmagnesium bromide, the 7-phenyl-6,7-dihydro derivative 82. Nucleophilic substitution of the methiodide 79 with potassium cyanide resulted in the formation of 9-cyano-6,9-dihydroderivative 83, which can be oxidized by iodine to 9-cyano-l,2,5-selenadiazolo [3,4-/]quinoline methiodide 84. All the reactions proceeded in moderate yields (81IJC648). 

Treatment of an alkaline solution of quinoxalin-2-one or quinoxa-line-2,3-dione with an alkyl iodide or sulfate results in A-methylation. Thus methylation of 3-aminoquinoxalin-2-one (74) with methyl sulfate and alkali gives 3-amino-l-methylquinoxalin-2-one (75) and not as previously reported the isomeric 0-methyl derivative. ... 

Treatment of 49 with a strong base such as sodium ethoxide serves to remove the last proton on the heterocyclic ring. Alkylation of the resulting carbanion with allyl bromide affords aloxidone (50) methyl sulfate on the carbanion gives trimetha-dione (51), while ethyl sulfate yields paramethadione (52). ... 

Alkylation of the 5(4)-nitro compound with methyl sulfate in nonpolar solvents affords dimetridazole (91), ° an antitrichomonal agent used in veterinary practice. Alkylation with chlorohydrin leads to metronidazole (92), a drug that has found widespread use in the treatment of vaginal trichomoniasis. Finally, alkylation by means of iv-(2-chloroethyl)morpholine affords nitrimida-zine (93),... 

Chemical Name 4-Amino-6-methoxy-1-phenylpyridazinium methyl sulfate Common Name —... 

This compound may be produced by reacting o-chlorobenzophenone with acetonitrile in the presence of sodium amide or another strongly basic condensing agent, to form the nitrile of /3-phenyl-/3-o-chlorophenyl-hydracrylic acid, which is then hydrogenated to yield Tphenyl-l-o-chlorophenyl-S-aminopropanol-l. The latter intermediate compound is subsequently dimethylated with an agent such as methyl sulfate to provide the desired end product l-o-chlorophenyl-Tphenyl-S-dimethylaminopropanol. 

Chemical Name 4-(2-cyclohexyl-2-hydroxy-2-phenylethyl)-1,1-dimethylpiperazinium methyl sulfate... 

Benzoyl-N -methyl piperidine Diphemanil methyl sulfate... 

Clorazepate dIpotassium Cycrimine HCI Diphemanil methyl sulfate Feno profen Medazepam Procyclidine HCI Tamoxifen Tiemonium iodide 4-Bromobenzyl cyanide... 

Amezinium methyl sulfate Bromopride Cefoxitin sodium Cimetide... 

Hexamethonium bromide Hexocyclium methyl sulfate Ipronidazole Mefruside... 

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