Reaction with Methyl Iodide

Product elucidation of trimethyloxonium tetrafluoroborate and methyl iodide reactions with [l,2,3]triazolo[4,5- -pyridazines (Schemes 1-3) using mainly 2-D heteronuclear multiple bond correlation (HMBC). NMR... 

Methyl iodide, reactions with dialkyl-amino-thiazoles, 32. See also Alkylation 4-Methylthiazole, preparation of, from Na/NH3 reduction of 4-methyl-A-4-thiazoline-2-thione, 397 2-Methylthio-3-methylthiazolium salts, as catalyst for methylthiothiazole rearrangement, 406 Methylvinylketone, reaction of, with... 

The monobenzo compound (107 R1=R2 = H) forms a stable salt with methyl iodide. Reaction with TCNE results in elimination of hydrogen cyanide and formation of the tricyanovinyl derivative (107 R1 = C(CN)=C(CN)2, R2 = H) (67JA2626). 

Tetrabutylammonium tetrahydridoborate methyl iodide Reactions with dihorane in methylene chloride Prim, amines from nitriles... 

The synthetic access to a broad variety of nucleophilic [ C]methyl and [ " C]methylene synthons has significantly widened the scope of [ C]methyl iodide. Reaction with... 

Solution A was prepared by dissolving potassium acetate in methanol Solution B was pre pared by adding potassium methoxide to acetic acid Reaction of methyl iodide either with solu tion A or with solution B gave the same major product Why" What was this product" ... 

Amide 138 undergoes N-methylation by reaction with methyl iodide furnishing compound 139. However, the reaction with dimethyl sulfate provides O-methyl derivative 140 (Scheme 1) <2002CHE828>. 

Compound LII, on the other hand, can be made readily. It can have either the planar tricovalent boron structure or the "triptych tetra-covalent structure. In the latter structure the nitrogen is attached to boron and should be considerably less basic and nucleophilic than usual. It does in fact react unusually slowly with methyl iodide and with acids. The neutralization reaction with acids in water is not only slow but of zero order with respect to the acid. It is believed to have a rate-determining transformation from the triptych to the more basic form as the first step. 

N-(l-Methyl- and l-benzyl-3-pyrrolyl)aminomethylenemalonates (1476, R = Me, CH2Ph) were obtained in 91% and 91% yields, respectively, when 3-pyrrolylaminomethylenemalonate (1476, R = H) was reacted with methyl iodide or with benzyl bromide in DMF in the presence of sodium methylate at ambient temperature for 10-60 min (85JHC83 89JHC1029). N-Methyl derivatives (1477) were prepared in nearly quantitative yield under the previous conditions with methyl iodide if the reaction mixtures were stirred overnight. 

The KIE in the 2,6-dimethylpyridine-methyl iodide reaction is more than twice the KIE in the 2-methylpyridine-methyl iodide reaction. This is also consistent with a steric origin for the KIE because the 2,6-dimethylpyridine transition state must be much more sterically crowded than the 2-methyl-pyridine transition state. If the increase had been due to an inductive effect, the increase in the KIE in the 2,6-dimethylpyridine reaction should have been approximately twice the KIE for the 2-methylpyridine reaction, i.e. approximately 0.94 rather than the 0.91 that was observed. 

The steric rather than the inductive origin of the secondary deuterium KIE is also suggested because kH/kD = 0.994 per deuterium found in the per-deuteropyridine-methyl iodide reaction is smaller (less inverse) than the kH/kn = 0.988 per deuterium found for the 4-deuteropyridine reaction. A secondary inductive KIE should be more inverse when a deuterium is substituted for a hydrogen nearer the reaction centre, i.e. at the meta- or ortho-rather than at the para-position of the pyridine ring. Thus, if the KIE were inductive in origin, the KIE in the perdeuteropyridine reaction should be more inverse than that observed for the 4-deuteropyridine reaction. If the observed KIE were the result of a steric KIE, on the other hand, a less inverse KIE per deuterium could be found in the perdeuteropyridine reaction, i.e. a less inverse KIE per deuterium would be expected if there were little or no increase in steric hindrance around the C—H(D) bonds as the substrate was converted into the SN2 transition state. Since the KIE per D for the perdeuteropyridine reaction is less than 1%, the transition state must not be sterically crowded and the KIE must be steric in origin. Finally, the secondary deuterium KIEs observed in the reactions between 2-methyl-d3-pyridine and methyl-, ethyl- and isopropyl iodides (entries 3, 7 and 9, Table 17) are not consistent with an inductive KIE. If an inductive KIE were important in these reactions, one would expect the same KIE for all three reactions because the deuteriums would increase the nucleophilicity of the pyridine by the same amount in each reaction. The different KIEs for these three reactions are consistent with a steric KIE because the most inverse KIE is observed in the isopropyl iodide reaction, which would be expected to have the most crowded transition state, and the least inverse KIE is found in the methyl iodide reaction, where the transition state is the least crowded. 

The synthesis of yet another example begins with the allylation of the enamide (21-2) with methyl iodide. Reaction of this intermediate (23-1) as above with the ami-nopyrrazole (23-2) leads to the formation of the fused pyrimidinopyrrazole (23-3). This last productis is next acylated with thiazole-carboxillic acid (23-4) in the presence of aluminum chloride. There is thus obtained the sleep inducing agent indiplon (23-5) [24]. 

In the case of monomer 23 it appears that an equilibrium exists between ionic and covalent propagating species in polymerisations initiated by methyl iodide, though with OT counterion only ionic intermediates are observed. Presumably therefore the effective nucleophilicity of this monomer is very similar to that of I. N-(2-iodopropyl)-N-methyl formamide was prepared from an equimolar reaction of methyl iodide with 23, and H NMR spectroscopy in CD3CN showed that the following equilibrium was rapidly established ... 

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