Methyl iodide reaction with amines

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

Calculate activation energies for Sn2 reactions of ammonia and trimethylamine with methyl iodide via transition states ammonia+methyl iodide and trimethyl-amine+methyl iodide, respectively. Is attack by ammonia or trimethylamine more facile Rationalize your observation by comparing electrostatic potential maps for the two transition states. Which transition state requires more charge separation Is this also the higher-energy transition state ... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

The Hofmann elimination reaction was used by early organic chemists as the last step of a process known as a Hofmaim degradation—a method used to identify amines. In a Hofmann degradation, an amine is exhaustively methylated with methyl iodide, treated with silver oxide to convert the quaternary ammonium iodide to a quaternary ammonium hydroxide, and then heated to allow it to undergo a Hofmann elimination. Once the alkene is identified, working backwards gives the stmcture of the amine. 

SOLUTION TO 10a Although an amine cannot undergo an elimination reaction, a quaternary ammonium hydroxide can. The amine, therefore, must first be converted into a quaternary ammonium hydroxide. Reaction with excess methyl iodide converts the amine into a quaternary ammonium iodide, and treatment with aqueous silver oxide forms the quaternary ammonium hydroxide. Heat is required for the elimination reaction. 

Methyl iodide. See also lodomethane nucleophiUc substitution, 312, 359, 726 reaction with amines, 883... 

I-Alkenes. Reaction of a Grignard reagent or an alkyllithium in ether (refluxing) with dimelhyl(methylene)ammonium iodide results in formation of an alkyldimethylamine, which can be isolated as the methyl iodide salt. The amine is converted into a 1-alkene by oxidation to the oxide followed by pyrolysis at 160°. Examples ... 

Allow a mixture of 0-5 g. of the tertiary amine and 0-5 ml. of colourless methyl iodide to stand for 5 minutes. If reaction has not occurred, warm under reflux for 5 minutes on a water bath and then cool in ice water. The mixture will generally set solid if it does not, scratch the sides of the tube with a glass rod. RecrystaUise the solid product from absolute alcohol, ethyl acetate, acetone, glacial acetic acid or alcohol-ether. 

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). 

Fig. 3. Synthesis of fluoxetine (31). 3-ChIoro-I-phenyl-I-propanol reacts with sodium iodide to afford the corresponding iodo derivative, followed by reaction with methylamine, to form 3-(methyl amin o)-1-phenyl-1-propan 0I. To the alkoxide of this product, generated using sodium hydride, 4-fluorobenzotrifluoride is added to yield after work-up the free base of the racemic fluoxetine (31), thence transformed to the hydrochloride (51)...

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

The Hofmann elimination is useful synthetically for preparing alkenes since it gives the least substituted alkene. The reaction involves thermal elimination of a tertiary amine from a quaternary ammonium hydroxide these are often formed by alkylation of a primary amine with methyl iodide followed by reaction with silver oxide. The mechanism of the elimination is shown in Scheme 1.13 in this synthesis of 1-methyl-1-... 

A thio-substituted, quaternary ammonium salt can be synthesized by the Michael addition of an alkyl thiol to acrylamide in the presence of benzyl trimethyl ammonium hydroxide as a catalyst [793-795]. The reaction leads to the crystallization of the adducts in essentially quantitative yield. Reduction of the amides by lithium aluminum hydride in tetrahydrofuran solution produces the desired amines, which are converted to desired halide by reaction of the methyl iodide with the amines. The inhibitor is useful in controlling corrosion such as that caused by CO2 and H2S. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

For example, Mannich reaction of N-methylpyrrole affords the corresponding dimethylaminomethyl derivative (2) and treatment with methyl iodide affords the quaternary salt (3). Displacement of the quaternary amine by means of cyanide leads to the substituted... 

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