Aminomethylation water

Alkene isomerization Alkene hydrogenation Ketone hydrogenation Hydrogenation of cyanides Hydrogenation of nitro group Alkyne hydrogenation Aminomethylation Water gas shift reaction... 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

The reaction of nitrous acid with the amino group of the /3-amino alcohol—e.g. 1-aminomethyl-cyclopentanol 1—leads to formation of the nitrosamine 4, from which, through protonation and subsequent loss of water, a diazonium ion species 5 is formed " —similar to a diazotization reaction ... 

A solution of 192 g of 1 -phenethyl-4-hydroxy-4-aminomethyl piperidine in BOO cc of diethyi-carbonate is heated for 1 /i hours to refiux at about B0°C in the presence of sodium methylate (prepared for immediate use from 2 g of sodium). After this time, the ethyl alcohol formed during the reaction is slowly distilled while the maximum temperature is reached. The excess ethyl carbonate is distilled under reduced pressure. A crystallized residue Is then obtained, which is stirred with 400 cc of water and 400 cc of ether. The solution is filtered and 125 g (77.6%) of practically pure product melting at 232°C to 233°C, are obtained. 

A solution of 60 g of chromic anhydride in 40 ml of water was added dropwise to a suspension of 60 g of 2-aminomethyl-1 -methyl-5-chloro-3-(o-fluorophenyl)-indole hydrochloride in 600 ml of acetic acid. The mixture was stirred at room temperature overnight. To the reaction mixture was added 1.1 liters of ether and 1 liter of water and then 800 ml of 28% ammonium hydroxide, in small portions. The ethereal layer separated, washed with water, dried, and concentrated under reduced pressure. The residue (51.8 g) was dissolved in 100 ml of ethanol, and 100 ml of 20% ethanollc hydrogen chloride was added to the solution and the mixture was cooled. The precipitate was collected by filtration to yield 46.5 g of 1 -methyl-7-chloro-5-(o-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine-2-one hydrochloride, melt-... 

The resulting precipitate is collected by filtration, washed with water followed by ethanol, and dried to give 56.3 g of crude 2-aminomethyl-1 -methyl-5-nitro-3-phenyllndole hydrochloride, melting point 263°C to 267°C. 

The emulsifier aminomethyl propanol serves several purposes in hairspray. It acts as a buffering agent, controlling the acidity of the mixture to make it neutral ( pH balanced ). It also helps keep the polymers mixed with the water and alcohol, and controls the water solubility of the final mist, giving it the needed humidity resistance. It also helps to form the polymers into a gel. 

The Mannich condensation has traditionally been carried out in the presence of water as a three-component condensation involving a carbonyl compound (or related carbon nucleophile), formaldehyde, and a primary or secondary amine. The initial step is a condensation between the latter two reactants to form a mono- or dialkyl(methylene)ammonium ion which subsequently serves as the electrophilic partner in the reaction. With unsymmetrical ketones aminomethylation generally occurs at both positions to give mixtures of isomeric 3-amino ketones. The ratio of the isomers depends strongly on the structure of the ketone, and the more highly branched (3-amino ketone usually predominates. 

Another GC/MS method that was validated as a food tolerance method involved the determination of glyphosate and (aminomethyl)phosphonic acid (AMPA) in crops. In this method, glyphosate and AMPA residues are extracted from crop commodities (corn grain) with water. The extracts are then partitioned with dichloromethane,... 

Reduction of Poly(2-cyano-l,3-phenylene arylene ether), 20 Twenty-five mL of a 1.0 M solution of lithium aluminum hydride (LAH) in THF was cooled to 0° C before adding a solution of 1.64 g (5.0 meg) of 20 in 120 mL of THF. The resultant slurry was stirred for 24 h at 0° C, refluxed for 1 h, recooled to 5° C, and the excess LAH decomposed with 2 mL of water. The volume of the solution was reduced to 25 mL before pouring the mixture into 500 mL of 5% HC1 to dissociate the amine aluminum salt complex and precipitate the polymer. The polymer was recovered by filtration, reslurried in 20 mL of water and the pH adjusted to 9.0 with NaOH. After recovery of the neutralized polymer was recovered, it was dried in vacuo redissolved in CHC13, and reprecipitated using water as the nonsolvent. Final drying in vacuo for 24 h at 35° C left 1.2 g (72.3%) of poly[oxy-l,4-phenylene-(l-methylethylidene)-l, 4 -phenylene-oxy-(2"-aminomethyl)-l",3"-phenylene], 21, [n] (CHCI3) 0.3 dl/g. 

This method, although described for indoles, probably also worlds with 5-OH-tryptamine (serotonin), and 5-OH-DMT (bufotenin) with compounds of the latter type, orally active psilocybin analogs will be obtained in one step. Dissolve 5 g 5-OH-indole (or analog) in 25 ml ethanol. Add 5.5 g 33% aqueous dimethylamine (or other amine, e.g., piperidine) and add slowly dropwise with stirring 3.5 g 38% aqueous formaldehyde. Two minutes after the end of the addition shake with water and CHCI3 dry and evaporate in vacuum the CHClj phase to get 5 g oily 4-dimethyl-aminomethyl-5-OH-indole (1) (can chromatograph on 100 g alumina and elute with ethyl acetate). It has been claimed that this method does not work. 

II). To a warm solution of 5.2 g urotropine (hexamethylenetetramine) in 45 ml CHCI3, add 8 g (II) in 10 ml CHCI3 and let stand four hours at room temperature. Filter, wash with CHC13 and dry. Dissolve 2.3 g precipitate in 10 ml concentrated HCI and let stand two hours at room temperature. Add 30 ml water, basify with NaOH and extract with ether. Precipitate with dry HCI gas to get 3-Br-5-aminomethyl-isoxazole (III). Test for activity. Dissolve 8.8 g... 

III) and 5.6 g KOH in 60 ml methanol and reflux thirty hours. Dissolve in 100 ml water, acidify with dilute HCI evaporate in vacuum and dissolve residue in hot methanol to get 3-melhoxy-5-aminomethyl-isoxazole (IV). Test for activity. Convert (IV) to muscimole as described in method 1 or as follows reflux in concentrated HCI four hours and evaporate in vacuum (recrystallize-methanohtetrahydrofuran 1 1). Can add tetraethylamine to precipitate. 

The reaction of methyl 2-amino-2-deoxy-a-D-glucofuranoside and dimethyl methoxymethylenemalonate in water for 5 h gave aminomethyl-enemalonate (37) in 92% yield (87M14). 

Benzoic acids substituted with a basic side chain also are also of interest as pro-moieties whose physicochemical properties and rates of enzymatic hydrolysis can readily be modulated. A number of drugs have been converted to prodrugs with this type of pro-moiety, e.g., hydrocortisone, prednisolone, acyclovir, chloramphenicol, and paracetamol [148] [149], These prodrugs appear well suited as parenteral formulations, being water-soluble, stable in slightly acidic solution, and readily hydrolyzed enzymatically. As examples, we consider here the hydrolysis in human plasma of a number of (aminomethyl)ben-zoates of metronidazole (8.109-8.115, Sect. 8.5.5.1, Table 8.9) [138], These prodrugs are very rapidly activated, which may be beneficial for parenteral administration. However, this type of pro-moiety may be cleaved too rapidly after oral administration to be of interest for poorly absorbed drugs. 

Pliotolytic. Bussacchini et al. (1985) studied the photolysis (7, = 254 nm) of phenmedipham in ethanol, ethanol/water, and hexane as solvents. In their proposed free radical mechanism, homolysis of the carbon-oxygen bond of the carbamate linkage gave the following photoproducts 3-(hydroxylphenyl)carbamic acid methyl ester, m-toluidine, 2-hydroxy-4-aminomethyl benzoate, 3-hydroxy-5-aminomethyl benzoate, 2-amino-4-hydroxymethyl benzoate, and 2-amino-6-hydroxymethyl benzoate. 

Thiadiazole, the 2-amino, 2-aminomethyl, 2-aminomethyl-5-methyl, and 2,5-dimethyl derivatives are all soluble in water. Generally, as the size of the substituents on carbon increases, the aqueous solubility decreases and the solubility in organic solvents increases. 

Nylon 22 has a lower Tm (285 ). greater flexibility, and lower water absorption than nylon 6. Cycloaliphatic polyimtdes. such as those produced by the condensation of 2, 4-bis(aminomethyl) cyclohexane and suberic acid, have relatively low water absorption and excellent nonconductive electric nronentes. 

Fig. 9. 600 MHz EXSY spectrum showing the exchange of magnetization between ammonium protons and two distinct water components in a peptidyl-water cluster bound to -aminomethyl polystyrene resin swollen in DMF-d1. Reproduced with permission from Ref. 88. Copyright 2001 American Chemical Society.

To a 200-mL, round-bottomed flask equipped with magnetic stirring, 2-(aminomethyl)pyridine (Acros, 8 mL, 80 mmol) is added to a solution of picolyl chloride HCl (25.6 g, 160 mmol) in distilled water (40 mL). Sodium hydroxide (31.0 mL of a 10 M solution, 320 mmol) is added dropwise (approximately 5 drops/min) over a period of 2 h using an addition funnel. The flask is then placed in a 70°C oil bath for 30 min. The solution is removed from the oil bath and is cooled to room temperature. The resulting dark red solution is transferred to a separatory funnel and extracted with three 150-mL portions of CHC13. The combined extracts are dried over anhydrous Na2S04. After filtration, the CHC13 is removed on a rotary evaporator. The... 

When ammonia or primary amines are used, the product amines may participate in further aminomethylation, resulting in the formation of a mixture of amines. Other byproducts (aldehydes, alcohols, carboxamides) may also be formed. The reaction to produce tertiary amines from secondary amines, however, is fairly selective. Aminomethylation of ethylene with piperidine was reported to form /V-propyl-piperidine with 75% yield when the reaction was carried out in the presence of [Fe(CO)5] and water without an external source of CO (170°C, 14 h).207... 

Pyrrole and indole rings can also be constructed by intramolecular addition of nitrogen to a multiple bond activated by metal ion complexation. Thus, 1-aminomethyl-l-alkynyl carbinols (obtained by reduction of cyanohydrins of acetylenic ketones) are cyclized to pyrroles by palladium(II) salts. In this reaction the palladium(II)-complexed alkyne functions as the electrophile with aromatization involving elimination of palladium(II) and water (Scheme 42) (81TL4277). 

---