With Methyl Iodide

Diaryl ditellurium compounds refluxed with an excess of methyl iodide are converted to aryl methyl tellurium diiodides. 

Irgolic Organo Tellurium Compounds with 2 Te —C Bonds or 1 Te = C Bond 

4-Ethoxyphenyl Methyl Tellurium Diiodide A mixture of 1 g (1.98 mmol) of bis[ethoxyphenyl] ditcllurium and 50 g (0.35 mol) of methyl iodide is heated under reflux for 0.5 h. The yellow precipitate of dimethyl 4-ethoxyphenyl telluronium iodide is filtered off. Light petroleum ether is added to the cold filtrate to crystallize the product yield 0.34 g (33%) m.p. 108°. 

The reactions of diaryl ditelluriums with other alkyl halides have not been investigated. 

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Purdie t Methody also chiefly for hydroxy compounds. The substance is mixed with a small excess of dry silver oxide, and then shaken (or, if necessary, heated) with methyl iodide, a smooth methylation usually occurring. 

When the methyl-phenyl-pyrazolone is heated with methyl iodide in methano-lie solution, it acts in the form (D), the — NH— group undergoing methy lation, with the formation of the hydriodide of 2,3-dimethyl- l-phenyl-5 Pyrazolone, or antipyrine (F), a drug used (either as the free base or as the... 

Members of Classes (i), (ii) and (iv) usually react readily with methyl iodide to give methiodides, i.e., quaternary ammonium iodides. 

Similar results are obtained with methyl iodide, ethyl bromide, ethyl iodide, iodoform, carbon tetrachloride, and benzyl chloride. 

Nucleophilic reactivity of the sulfur atom has received most attention. When neutral or very acidic medium is used, the nucleophilic reactivity occurs through the exocyclic sulfur atom. Kinetic studies (110) measure this nucleophilicity- towards methyl iodide for various 3-methyl-A-4-thiazoline-2-thiones. Rate constants are 200 times greater for these compounds than for the isomeric 2-(methylthio)thiazole. Thus 3-(2-pyridyl)-A-4-thiazoline-2-thione reacts at sulfur with methyl iodide (111). Methyl substitution on the ring doubles the rate constant. This high reactivity at sulfur means that, even when an amino (112, 113) or imino group (114) occupies the 5-position of the ring, alkylation takes place on sulfiu. For the same reason, 2-acetonyi derivatives are sometimes observed as by-products in the heterocyclization reaction of dithiocarba-mates with a-haloketones (115, 116). 

Alkylation of A-4-thiazoline-2-one may yield O-R or N-R derivatives according to experimental conditions. With diazomethane in ethanol O-raethylation takes place (29. 36. 214). N-Methylation is reported when a basic solution of A-4-thiazoline-2-one reacts with methyl iodide or dimethylsulfate (21, 29, 215, 216), Reaction of l-chloro-2-dimethyl-aminoethane with the sodium salt of 4 R-A-4-thiazoline-2-one (91) in alcohol, first claimed to yield the aminoalkylether (217, 218), was shown after infrared investigation to give the N-substituted derivative (92) (107), even when R Ph (Scheme 45). More probably the site of reaction in... 

Methylamino)-4-methylselenazole was obtained by methylation of the potassium salt of 2-acetamido-4-methylselenazole with methyl iodide, followed by hydrolysis (Scheme 13) (26). 

In 1882, Will (90), by reacting CS2 with the product (56) resulting from the condensation of dibromoethane with N,N -diphenylthiourea, obtained the first derivative of thiazolidine-2-thione (57). He observed the reaction of 57 with methyl iodide to afford an addition compound (58). 

The first kinetic results in the area were obtained by studying the quatemization of 4-alkyl-, 5-alkyT, and 2-alkylthiazoles with methyl iodide (253-255). A deeper and more exhaustive study of this reaction has been carried out recently with more elaborate substrates (152). 

If the rate constants for quaternization of 2-alkylthiazoles depended on electronic factors, they would all be greater than that of thiazole, which has the low est pK. and all of the same order. The decrease in rate constants that is observed is attributed wholly to steric effects. In Table III-50 we report the main parameters for the reaction of 2-alkylthiazoles with methyl iodide. 

TABLE m-50. RATE CONSTANTS AND ACTD ATION PARAMETERS FOR THE REACTION OF 2-ALKYLTHl AZOLES WITH METHYL IODIDE IN NITROBENZENE (256)... 

TABLE in-52. KINETIC DATA FOR THE OUATERNI-ZATION OF 2- AND 4-ALKYLTHIAZOLES WITH METHYL IODIDE IN NITROBENZENE AT 25°C (256)... 

The quatemization of 5-alkylthiazoles with methyl iodide in nitrobenzene has been studied (254) results are summarized in Table III-54. 

TABLE ra-54. RATE AND ACTIVATION CONSTANTS FOR THE REACTION OF 5-ALKYLTHlAZOLES WITH METHYL IODIDE IN NITROBENZENE. (254). 

As we have seen the nucleophile attacks the substrate m the rate determining step of the Sn2 mechanism it therefore follows that the rate of substitution may vary from nucleophile to nucleophile Just as some alkyl halides are more reactive than others some nucleophiles are more reactive than others Nucleophilic strength or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate By measuring the rate at which various Lewis bases react with methyl iodide m methanol a list of then nucleophihcities relative to methanol as the standard nucleophile has been compiled It is presented m Table 8 4... 

It looks as though all that is needed is to prepare the acetylenic anion then alkylate it with methyl iodide (Section 9 6) There is a complication however The carbonyl group m the starting alkyne will neither tolerate the strongly basic conditions required for anion formation nor survive m a solution containing carbanions Acetyhde ions add to carbonyl... 

Physostigmme an alkaloid obtained from a West African plant is used in the treatment of glaucoma Treatment of physostigmme with methyl iodide gives a quaternary ammonium salt What IS the structure of this salt" ... 

Ethers are formed under conditions of the Williamson ether synthesis Methyl ethers of carbohydrates are efficiently prepared by alkylation with methyl iodide m the presence of silver oxide... 

The aHphatic iodine derivatives are usually prepared by reaction of an alcohol with hydroiodic acid or phosphoms trHodide by reaction of iodine, an alcohol, and red phosphoms addition of iodine monochloride, monobromide, or iodine to an olefin replacement reaction by heating the chlorine or bromine compound with an alkaH iodide ia a suitable solvent and the reaction of triphenyl phosphite with methyl iodide and an alcohol. The aromatic iodine derivatives are prepared by reacting iodine and the aromatic system with oxidising agents such as nitric acid, filming sulfuric acid, or mercuric oxide. 

Analytical methods iaclude thin-layer chromatography (69), gas chromatography (70), and specific methods for determining amine oxides ia detergeats (71) and foods (72). Nuclear magnetic resonance (73—75) and mass spectrometry (76) have also been used. A frequentiy used procedure for iadustrial amine oxides (77) iavolves titratioa with hydrochloric acid before and after conversion of the amine to the quaternary ammonium salt by reaction with methyl iodide. A simple, rapid quaHty control procedure has been developed for the deterrniaation of amine oxide and unreacted tertiary amine (78). 

Methyl-2-Pyrrolidinone. N-Meth5l-2-pyrrohdinone [872-50-4] (44) (NMP or methyl-2-pyrrohdone, M-Pyrol) was fkst reported in 1907 as prepared by alkylation of 2-pyrrohdinone with methyl iodide (81). The present commercial route, ie, condensation of butyrolactone with methylamine, was first described in 1936 (50). 

Quaternary ammonium alkyl ethers are prepared similarly an alkaline starch is reacted with a quaternary ammonium salt containing a 3-chloto-2-hydtoxyptopyl or 2,3-epoxyptopyl radical. Alternatively, such derivatives can be prepared by simple quaternization of tertiary aminoalkyl ethers by reaction with methyl iodide. Sulfonium (107) and phosphonium (108) starch salts have also been prepared and investigated. Further work has explained the synthesis of diethyl aminoethyl starch (109) as well as the production of cationic starches from the reaction of alkaline starch with... 

In the case of nicotinamide, the color yield is often low. This problem can be circumvented by either hydrolysis to nicotinic acid or by conversion of the amide to a fluorescent compound. Treatment of nicotinamide with methyl iodide yields the quaternary ammonium salt, /V-methyl nicotinamide (5). Reaction of this compound with acetophenone yields a fluorescent adduct (49). Other carbonyl compounds have also been used (50—54). 

IV-Methylation of polysubstituted pyridazinones is frequently accompanied by some side reactions, mainly substitutions. For example, methylation of 4-nitro-5,6-diphenyl-pyridazin-3(2//)-one with methyl iodide in the presence of sodium methoxide affords... 

Alkylations of cinnolin-4(lf/)-one (8) with methyl iodide, ethyl iodide, dimethyl and diethyl sulfates, isopropyl bromide, benzyl chloride, etc. take place predominantly at position 2 to give 2-alkyl-4-hydroxycinnolinium anhydro salts (83), together with small amounts of l-methylcinnolin-4-one (84). 

Table 10 Experimental and Calculated Ni/N Methylation Product Ratios for the Reaction of 3-X,6-Y-Pyridazines with Methyl Iodide in Acetonitrile...

Quatemization of various pyridazinethiones and pyridazinyl sulfides is dependent on the substituents attached to the pyridazine ring. For example, 3-methylthiopyridazine and 6-methyl-3-methylthiopyridazine react with methyl iodide to form the corresponding 1-methyl-3-methylthio and l,6-dimethyl-3-methylthio derivatives (85). On the other hand, if a larger group, such as methoxy or phenyl, is attached at the 6-position, quaterniza-tion takes place at position 2 to give 6-substituted 2-methyl-3-methylthiopyridazines (86 Scheme 24). 

AIkyI-substituted pyridazine-3(2//)-thiones undergo reaction with methyl iodide at the sulfur atom. Methylation of 4,5-diaminopyridazine-3(2ff)-thione with excess methyl iodide produces 4,5-diamino-l-methyIthiopyridazinium iodide (81JOC2467). 

The Reissert compound obtained from phthalazine and potassium cyanide in the presence of benzoyl chloride can be converted with methyl iodide and sodium hydride in DMF into... 

Although it is seldom used, esterification of pyrimidinecarboxylic acids proceeds normally. Conditions are illustrated by the conversion of pyrimidine-4-carboxylic acid (181 R = H) into its methyl ester (181 R = Me) by methanol/sulfuric acid (47%), methanol/hydrogen chloride (80%), or by diazomethane (ca. 100%) (60MI21300). The isomeric methyl pyrimidine-2-carboxylate is formed by treatment of the silver salt of the acid with methyl iodide. Higher esters, e.g. (182 R = Bu), are usually made by warming the acid (182 R = H) with the appropriate alcohol and sulfuric acid (60JOC1950). 

Both thermal and Hilbert-Johnson reactions occur quite readily in 2- and 4/6-alkoxyquinazolines. For example, distillation of 2,4-bis-/3-diethylaminoethoxyquinazoline in vacuo yields l,3-bis-/3-diethylaminoethylquinazolin-X4(l/J,3H )-dione (60JCS3546). A complicated example is furnished by heating a tetramethoxybipyrimidine with methyl iodide to give four separable products progressively (81AJC1157). 

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