Methyl iodide, halide displacement

F-Methylation. Phosphonium salts are prepared by the quat-ernization of phosphines with methyl iodide. The displacement reaction is usually conducted in polar solvents such as acetonitrile or DMF. Dialkyl phosphonates are prepared from the reaction of trialkyl phosphites with alkyl halides, commonly known as the Arbuzov reaction. For example, diisopropyl methylphosphonate is prepared by heating a mixture of methyl iodide and Triisopropyl Phosphite (eq 34). ... 

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... 

Route A 1- is very convenient for the substitution of OH groups by bromide or iodide. The reaction conditions are relatively mild (acetonitrile, room temperature, and reflux for 1—3 h, neutral medium). The activating halide (methyl iodide, ally or benzyl bromide) is added in excess (5 equivalents) or in large excess (10 equivalents) when the resultant halide is nearly as reactive as the activating halide. The imidazolium-iV-carboxylates are the important intermediates, which undergo a displacement reaction to give the halides,... 

A compound that includes an aminopyrimidine ring as well as the quaternary salt present in thiamine shows preferential inhibition of absorption of that co-factor by coccidia parasites over uptake by vertebrates. The compound is thus used in poultry where coccidiosis is an economically important disease. Condensation of ethoxymethylenemalononitrile (42-1) with the amidine (42-2) leads to the aminopyrimidine (42-4), probably via the intermediate addition-elimination intermediate (42-3). The nitrile group is then reduced to the methylamino derivative (42-5) by means of hthium aluminum hydride. Exhaustive methylation, for example by reaction with formaldehyde and formic acid, followed by methyl iodide leads to the quaternary methiodide (42-6). The quaternary salt is then displaced by bromine, and the resulting benzyhc-like cylic halide (42-7) is displaced by 2-picoline (42-8). There is thus obtained amprolium (42-9) [43]. 

Depending on the relative nucleophilicities, [Nu]50% ranges from micromolar to molar concentrations (Table 13.5). Although these values represent only order-of-magnitude estimates, they allow some important conclusions. First, in uncontaminated freshwa-ters (where bicarbonate typically occurs at about 10"3 M, chloride and sulfate occur at about 10 4 M, and hydroxide is micromolar or less, Stumm and Morgan, 1996), the concentrations of nucleophiles are usually too small to compete successfully with water in SN2 reactions involving aliphatic halides. Hence the major reaction will be the displacement of the halide by water molecules. In salty or contaminated waters, however, nucleophilic substitution reactions other than hydrolysis may occur Zafiriou (1975), for example, has demonstrated that in seawater ([CL] 0.5 M) an important sink for methyl iodide is transformation to methyl chloride ... 

Thieno[3,2-d]pyrimidine-2(l//)-thiones 217-219 and -4(3//-thiones 245 were S-methylated smoothly with methyl iodide in base to the corresponding 2-methylthio (82EUP43054 89CPB1197) and 4-methylthio (86JHC 1757) compounds. 5-Alkylation of thieno[3,2-d]pyrimidin-4(3//)-one-2(l//)-thione 223 with alkyl halides in dilute sodium hydroxide solution afforded 2-alkylthio derivatives 284. Nucleophilic displacement of the alkyl-thio group in compound 284 by primary amines has also been reported (90EUP404356). 

Many useful reactions take place by the SN2 mechanism. The reaction of an alkyl halide, benerallty OT th6 such as methyl iodide, with hydroxide ion gives an alcohol. Other nucleophiles convert Sn2 Reaction alkyl halides to a wide variety of functional groups. The following table summarizes some of the types of compounds that can be formed by nucleophilic displacement of alkyl halides. 

Phenylthiomethyllithium (2a) was used for the homologation of primary halides in a two-step sequence first halogen displacement by reagent (2a) or the organocuprate derivative (in the case of allylic compound) and then replacement of the phenylthio group by iodo by heating the sulfide with a large excess of methyl iodide in 1 M sodium iodide solution in DMF (Scheme 16). 

If an organic chemist wanted to put a methyl group on a nucleophile, methyl iodide would most likely be the methylating agent used. Of the methyl halides, methyl iodide has the most easily displaced leaving group because 1 is the weakest base of the halide ions. In addition, methyl iodide is a liquid, so it is easier to handle than methyl bromide or methyl chloride. The reaction would be a simple Sn2 reaction. 

A series of methyl- and ethyl-substituted ammoniomethyl iodides (68a-d) was also examined in order to determine the relative rates of displacement at ethyl versus methyl. Although the methyl derivative is more reactive than the ethyl derivative, the rate ratios for this ammonium dealkylative 5n2 process are small compared with those for displacement of halide ion from MeX versus EtX. In contrast, the relative reactivity of the allyl group in substrate (68e) is much greater than has been observed for halide displacement reactions. 

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