Methylamines ammonium compounds

Methylene chloride is easily reduced to methyl chloride and methane by alkaU metal ammonium compounds in Hquid ammonia. When the vapor is contacted with reduced nickel at 200°C in the presence of excess hydrogen, hydrogen chloride and elementary carbon are produced. Heating with alcohoHc ammonia at 100—125°C results in hexamethylenetetramine, (CH2) N4, a heterocycHc compound with aqueous ammonia at 200°C, hydrogen chloride, formic acid, and methylamine are produced. 

Methylamine occurs in herring brine 2 in crude methyl alcohol from wood distillation,3 and in the products obtained by the dry distillation of beet molasses residues.4 It has been prepared synthetically by the action of alkali on methyl cyanate or iso-cyanurate 5 by the action of ammonia on methyl iodide,6 methyl chloride,7 methyl nitrate,8 or dimethyl sulfate 9 by the action of methyl alcohol on ammonium chloride,10 on the addition compound between zinc chloride and ammonia,11 or on phos-pham 12 by the action of bromine and alkali on acetamide 13 by the action of sodamide on methyl iodide 14 by the reduction of chloropicrin,15 of hydrocyanic or of ferrocyanic acid,16 of hexamethylenetetramine,17 of nitromethane,18 or of methyl nitrite 19 by the action of formaldehyde on ammonium chloride.20... 

Numerous compounds can provide general cryoprotection to proteins, when used at concentrations of several hundred millimolar. These include sugars, polyols, amino acids, methylamines, and salting-out salts (e.g., ammonium sulfate) [59,61,68-70]. Based on the results of freeze-thawing experiments with LDH and PFK and a review of the literature on protein freezing. Carpenter and Crowe [59] have proposed that this cryoprotection can be explained by the same universal mechanism that Timasheff and Arakawa have defined for solute-induced protein stabilization in nonfrozen, aqueous solution (reviewed in [4,70,78,79]). 

Cyano-6-methylaminopyrazine was also prepared from the chloro compound with methylamine hydrochloride and sodium hydroxide in aqueous dioxane (945) and 2-cyano-6-(2, 2 -dimethylhydrazino)pyrazine was prepared similarly (945). 2-Chloro-6-cyanopyrazine with methanol (and similarly with ethanol) and triethylamine gave 2-methoxy-6-(C-methoxyformidoyl)pyrazine (32) [see Section 5D(2)], and 2-chloro-6-carbamoylpyrazine with concentrated aqueous ammonia at 170-175° gave 2 -amino-b-carboxypyrazine (744). 2-Chloro-3-cyano-5,6-diphenylpyrazine with ammonium hydroxide and potassium iodide formed 2-amino-3-carbamoyl-5,6-diphenylpyrazine, but on fusion with ammonium acetate it gave 2-amino-3-cyano-5,6-diphenylpyrazine (848). 

The Birch and Benkeser reactions of some unsaturated organic compounds [318 and references therein], which consist of a reduction by sodium or lithium in amines, can be mimicked electrochemically in the presence of an alkali salt electrolyte. The cathodic reaction is not the deposition of alkali metal on the solid electrode but the formation of solvated electrons. Most of the reactions described were performed in ethylenediamine [319] or methylamine [308,320]. A feature of these studies is variety introduced by the use of a divided or undivided cell. In a divided cell, the product distribution appears to be the same as that in the classic reduction by metal under similar conditions. In contrast, in an undivided cell the corresponding ammonium salt is formed at the anode it plays the role of an in situ generated proton donor. Under such conditions, the proton concentration... 

To do the reaction, 50 grams of the bromo compound is poured into a beaker, and 200 ml of concentrated ammonium hydroxide (28% NH3) or 40% methylamine is added. Next, isopropyl alcohol is added with stirring until a nice smooth solution is formed. It is not good to add too much alcohol because a more dilute solution reacts slower. Now the mixture is poured into a pipe "bomb." This pipe should be made of stainless steel, and have fine threads on both ends. Stainless steel is preferred because the HBr given off in the reaction will rust regular steel. Both ends of the pipe are securely tightened down. The bottom may even be welded into place. Then the pipe is placed into cooking oil heated to around ISOoC. This temperature is maintained for about 3 hours or so, then it is allowed to cool. Once the pipe is merely warm, it is cooled down some more in ice, and the cap unscrewed. 

Internalization affords the next opportunity to ameliorate the toxic actions of BoNT. A number of pharmacological agents have been examined for inhibition of this process with various degrees of success. Simpson (1983) demonstrated that pretreatment of phrenic nerve-hemidiaphragm preparations with the lysosomotropic agents ammonium chloride or methylamine hydrochloride delayed the time-to-block of nerve-evoked muscle contractions after exposure to BoNT serotypes A, B, Cl, and TeNT. Incubation of nerve-muscle preparations with ammonium chloride and methylamine hydrochloride was effective if applied before, concurrently, or up to 20 min after toxin exposure. The efficacy of the lysosomotropic agents was reduced rapidly with further delays, such that no effect was observed if they were administered 30-35 min after toxin exposure. At optimal concentrations, these compounds produced a twofold delay in the time-to-block (Simpson, 1983). 

The preferred alkaline compounds for carrying out my invention are the alkali metal and alkaline earth metal oxides, hydroxides and carbonates, and these compounds are utilized in just sufficient amount to displace the desired amine or amines. It is obvious, of course, that if the mixture of amine salts also contains free mineral acid or an ammonium salt, an additional amoimt of alkali stoichiometrically equivalent to these substances must be added. I have also found that as alkaline reagents for accomplishing this separation it is possible to use other alkylamines or methylamines of different basicity. These amines may be used for displacement together with or in place of the alkalies above mentioned. For example, dimethylamine being more basic than trim-ethylamine may be utilized to displace triethylamine from its hydrohalide salts, when utilized in stoichiometrical proportions. Similarly, diethylamine may be utilized to displace mono and triethylamine from their hydrohalide combinations. 

Amidino and amino groups are converted in high yield into a fused pyrimidine ring on stirring the compound with (in this example, labelled) acetic formic anhydride (review of this compound [3823]. Amidino-nitriles react with either ammonium acetate or methylamine to give fairly good yields of the amino-pteridines (reviews of pteridines [3454, 3594, 3669]). Formic acid provides a carbon atom to complete the pyrimidine ring of a purine in this example of cyclization of an amino-amidine [2431]. No additional atoms are needed in the cyclization of the pyrazine (43.1) to a dihydropteridine [2159]. 

A process due to Sommelet540 is generally applicable (halomethyl)aryl compounds react with hexamethylenetetramine in alcohol or chloroform to yield quaternary ammonium salts, which decompose to aldehydes, formaldehyde, methylamine, and ammonia when boiled with water or dilute acid it is usually unnecessary to isolate the intermediate compound if the whole process is carried out in 1 1 acetic acid-water. 

Certain nitroso phenols and polyhydroxy compounds are exceptions where the exchange takes place under relatively mild conditions and sometimes without the need for a catalyst. For example,/7-nitrosophenol and ammonium salts, when heated on a steam-bath for 0.5 hour, give 50% of /7-nitrosoaniline, 1049.cf.1050 and l-nitroso-2-naphthol and aqueous methylamine solution at 35° give 90% of iV,iV-dimethyl-1 -nitroso-2-naphthylamine.1051 The easier reaction s due to the tautomerism of these phenols with the ketonic isomers, e.g.9 for nitrosophenol ... 

The salt is sometimes called methylamine hydrochloride, and its formula is written CH3NH2.HCI. The replacement of hydrogen in ammonium hydroxide by positive alkyl groups yields compounds which react with water and form bases much stronger than ammonium hydroxide. The accumulation of positive radicals in the quarternary ammonium bases results in the production of marked basic properties in these compounds. Tetra-methyl-ammonium hydroxide shows about as strong basic properties as potassium hydroxide. 

This synthetic procedure, using the hydrochloride salt of the amine and sodium cyanoborohydride in methanol, seems to be quite general for ketone compounds related to 3,4-methylenedioxyphenylacetone. Not only were most of the MD-group of compounds discussed here made in this manner, but the use of phenylacetone (phenyl-2-propanone, P-2-P) itself appears to be equally effective. The reaction of butylamine hydrochloride in methanol, with phenyl-2-propanone and sodium cyanoborohydride at pH of 6, after distillation at 70-75 °C at 0.3 mm/Hg, produced N-butylamphetamine hydrochloride (23.4 g from 16.3 g P-2-P). And, in the same manner with ethylamine hydrochloride there was produced N-ethylamphetamine (22.4 g from 22.1 g P-2-P) and with methylamine hydrochloride there was produced N-methylamphetamine hydrochloride (24.6 g from 26.8 g P-2-P). The reaction with simple ammonia (as ammonium acetate) gives consistently poor yields in these reactions. 

While Frankland was evolving his theory of combining power, the new type theory was making its appearance. The primary amines methylamine and ethylamine had been prepared in 1849 by Charles Adolphe Wurtz (1817-1884), and he recognised that these compounds were related to ammonia. The work was continued by August Wilhelm von Hofmann (1818-1892), who in 1851 prepared primary, secondary and tertiary amines and also quaternary ammonium salts. He classified these as belonging to the ammonia type (Figure 8.5). 

In principle, although not always in practice, reaction intermediates may be isolated. They exist at minima on the energy curve and have a definite lifetime, which may be long or short. For example, in the reaction of an excess of bromoethane with methylamine to give the ammonium salt [Et3NMe]+Br (8.6), the intermediates ethylmethylamine and diethylmethylamine are stable compounds, and if the reaction was stopped at an appropriate time, they could be isolated. Other intermediates, such as the carbocation, 8.2, are short lived and unstable and cannot be isolated, although they can sometimes be observed spectroscopically (Figure 8.7). 

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