Methyl iodide amines from

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. 

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-... 

On the basis of fundamental experiments (see Section IV,A,2) some indenobenzazepine alkaloids have been efficiently synthesized from the corresponding protoberberines via 8,14-cycloberbines. For example, the cycloberbine 428 derived from the protoberberine 427 was heated with methanesulfonic acid in aqueous tetrahydrofuran to afford a 2 1 mixture of cis- and trans-indenobenzazepines 429 in 92% yield (Scheme 85). The mixture was methylated with methyl iodide to give the cts-N-methyl derivative 430 and the unchanged trans secondary amine (21%), which was very difficult to methylate and which gave the /V-methyl derivative only in 6% yield even on treatment with dimethyl sulfate for 43 hr. Contrary to the ordinary cases (Section IV,A,2), the trans derivative did not isomerize to the cis isomer 430 under various acidic conditions. Debenzylation of 430 by hydrogenolysis afforded fumarofine (417), which was converted to O-methylfumarofine (316) by methylation with diazomethane (215). 

Hindered di-t-alkylamines RNHBu1 (R = t-Bu, t-octyl or 1-adamantyl) have been synthesized from t-alkylamines as follows. Reaction with peracetic acid gave the nitrosoalkanes RNO, which were treated with t-butyl radicals, generated from t-butylhydrazine and lead(IV) oxide, to yield t-butyloxyhydroxylamines. Reduction with sodium naphthalide in THF gave the products (equation 12). The di-t-alkyl-amines are inert to methyl iodide and dimethyl sulphate but can be alkylated by methyl fluorosulphonate42. 

V-Methyl-/V-(2-perlhioroalkyl)ethy I amines 17 (R = C4F9, QT n or C-xI i 7) were prepared from the azides 16 by sequential reaction with triphenylphosphine, methyl iodide and aqueous potassium hydroxide45. 

The A -methyl derivative (32) was obtained from 31 via a Leuckart reaction and isolated as its hydrochloride 32 is also formed in the Hoffmann-Lbflfterreaction(photolysisinsulfuricacid)ofthei r-chloramine (33), since after separation of secondary amines and addition of methyl iodide a 10% yield of the methiodide (34) was obtained. The secondary amine (31) was also converted to its A-acyl and JV -nitroso derivatives (35-37) and (38), respectively, by conventional procedures. Free-radical chlorination of 37 gave the ca o-2-chloro derivative (39) and... 

Solid tertiary amines and imines may be quantitatively alkylated by gas-solid and solid-solid techniques. Methylation of quinuclidine (176) to give the methoiodide 177 is achieved waste-free by exposure of 176 to a stoichiometric amount of methyl iodide vapor (Scheme 23). Difficulties with the disintegration of the crystals of 177 from those of 176 (reaction step 3) are overcome by ultrasound treatment from a cleaning bath at 20 °C [22]. Numerous applications of this technique to tertiary amines can be envisaged. However, solid Troeger s base (with interlocked layers, i.e., no possibility for molecular migrations) is not alkylated by methyl iodide vapor unless an excess of the vapor is applied to induce intermediate (partial) liquefying of the solid [22]. 

The catalyst is generally a palladium compound promoted with a trivalent amine or phosphine in the presence of methyl iodide as described earlier. Systems proven to bias acetaldehyde are utilized, of course (e.g. see Table I, run 12). A yield of 85% acetaldehyde from methyl acetate is typical by this method. It can be utilized in stoichiometric addition to easily prepared acetic anhydride resulting in EDA formation. When considering that the "boiling pot" reaction by-products are recyclable acetic acid, acetic anhydride and small amounts of EDA, the yield to vinyl acetate related products is 95%. 

The hydroxyquinoline (39-2) provides the starting material for a quinolone that incorporates a hydrazine function. Reaction of (39-2) with 2,4-dintrophenyl O-hydroxylamine ether (41-1) in the presence of potassium carbonate leads to a scission of the weak N-O hydroxylamine bond by the transient anion from the quinolone the excellent leaving character of 2,4-dinitrophenoxide adds the driving force for the overall reaction, resulting in alkylation on nitrogen to form the hydrazine (41-2). The primary amine is then converted to the formamide (41-3) by reaction with the mixed acetic-formic anhydride. Alkylation of that intermediate with methyl iodide followed by removal of the formamide affords the monomethylated derivative (41-4). Chlorine at the 7 position is then displaced by A-methylpiperazine and the product saponified. There is thus obtained amifloxacin (41-6) [48]. 

The Mannich reaction is a particularly good method of introducing a reactive functional group into a sensitive aromatic nucleus. The reaction has been very useful in ferrocene chemistry. Treatment of chromium acetylacetonate under Mannich conditions yielded a tris-V,N-dimethylaminomethyl chelate (XXXIII). This remarkable substance was very difficult to purify because of its extreme solubility in all solvents ranging from n-heptane to water. The trisamino chelate (XXXIII) is a deep purple, hydroscopic oil and behaves like a typical organic amine. Reaction of this amine with methyl iodide afforded a trisquater-nary ammonium salt (XXXIV), soluble in water but insoluble in organic solvents. When this salt (XXXIV) was treated with cyanide ion, trimethylamine was lost and the cyanomethyl chelate (XXXV) was formed. 

EXTENSIONS AND COMMENTARY N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide (mp 223-224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175-177 °C from ) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above. 

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