Aminomethylation solvents

A generally applicable reaction scheme naturally cannot be given. The reaction mechanism of one particular carbinolamine with a particular reagent can depend on the reaction conditions in nonpolar solvents, the nondissociated carbinolamine obviously reacts (Sj 2 mechanism). In polar solvents, on the other hand, the mesomeric cation reacts (S l mechanism). Formally all these reactions belong to the general class of aminomethylation. The reaction products can be considered to be Mannich bases. ... 

Acid-catalyzed aminomethylations of 5W-dibenz[/>,/]azepine (5) in ethanolic solution with formaldehyde and a secondary amine yield the 2-(aminoalkyl) derivatives, e.g. 6.186 If acetic acid is used as the solvent, however, then 2,8-bis(aminoaIkylatiou), e.g. formation of 7, results. 

To remove carboxylic acid, the crude product is redissolved in 20 mL of methylene chloride and is shaken for 30 min with 1 g of aminomethylated polystyrene resin with a substitution of 1.02 mmol/g, available from Novabiochem (Note 3). After filtration and washing of the resin with 50 mL of methylene chloride, the filtrates were collected together in a 250-mL flask and the solvent was removed on a rotary evaporator. 

The most successful approach to producing an aminomethyl derivative was the Gabriel synthesis. A phthalimide substituent can be introduced by Sn2 displacement of the chloride on 17 with potassium phthalimide under homogeneous conditions in DMF. The reaction is quantitative in all D.F. ranges and the phthalimldo-methyl intermediates, 18, are quite soluble in organic solvents. 

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. 

A soln of H-D-Abu-(Me)Arg(Tos)-Gly-Asp(OtBu)-Mamb-OH [Mamb = 3-(aminomethyl)benzoic acid] (393 g, -0.35 mol) (note this quantity was quoted in the original literature but is clearly incorrect) and DIPEA (100 mL, 0.574 mol) in MeCN (3.4 L) was added dropwise to a stirred soln of HBTU (136 g, 0.359 mol) in MeCN (3 L) over 5.5 h. The mixture was stirred overnight, cooled to 0°C for 2 h, and the solids were collected by filtration and washed with MeCN/DIPEA (400 mL/4 mL). The crude product was dissolved in a soln of 18% MeOH in CHC13 (1215 mL) at 34 °C. Silica gel (527 g) was added to the soln, the slurry was filtered, and the filter cake was further extracted with 12% MeOH in CHC13. The filtrate was concentrated and the solvent was replaced with MeCN until GC analysis of the pot contents indicated the CHC13 content was <0.5%. The slurry was stirred at 34°C overnight, and the purified cyclic peptide was collected by filtration. The solids were washed with MeCN (200 mL) and dried yield 158.6 g (58%). 

A mixture of diethyl [(diphenylmethylene)aminomethyl]phosphonate (lmmol), Aliquat 336 (20mg, 0.05 mmol), the appropriate halide (1.5 mmol), and finely ground KOH (300 mg, 5 mmol) was stirred at rt, and the reaction progress was monitored by TLC (silica gel). The mixture was worked up by adding CH2C12 (10 mL) and slurrying with silica gel (50 mg). After filtration, the solvent was removed in vacuo, and the residue was purified by flash chromatography (silica gel). 

Amylamine Aminopentane Aminomethyl-butane,CSHU NH2. Several isomers are known, including Isoamylamine,(CH,)2 -CH-CHj-CHj-NHj. They can be prepd by the reaction of amyl chlorides with ammonia in the presence of alcohol as a mutual solvent. Datta Chatterjee(Ref 2) detd expln temps of amylaminepicrate and amylamineperchlo-rate and found them to be 270° and 262°, respectively... 

A-Methylimidazole (22.5 /il) was added to a mixture of Fmoc-glycinol (20.0 mg, 0.07 mmol), Fmoc-glycine (27.3 mg, 1.3 equiv.), and polystyryl-sulfonyl chloride resin (61.6 mg, 1.3 equiv., 1.49 mmol/g) in dichloro-methane (1 ml). After 2 h, aminomethylated PS-resin (138 mg, 2 equiv.) was added and the suspension shaken for 30 min. After filtration through a fritted filter, the resin was rinsed thoroughly with dichloromethane, and the combined solvents were concentrated to 3 ml. Amberlyte 15 (176 mg) was added and the suspension was shaken again for 30 min and filtered as described above. After evaporation of the solvent, the pure product was obtained as a colorless foam 93 % yield. 

Most reports in this category deal with asymmetric processes. For example, classic Mannich reaction of unmodified ketones, aqueous formaldehyde, and aromatic amines produces a-aminomethylation of the ketones in >99% ee, using L-proline as catalyst. 24 Methyl ketones regioselectively reacted on the methylene carbon. The method is simple, using wet solvents in the presence of air. 

Most polymers belonging to this class are water-soluble only in their protonated form. As a consequence, most potentiometric titrations of these polymers have been performed with OH starting from their hydrochlorides, either in water or in mixed solvents, such as water/dioxane, water/sulfolane, water/acetonitrile 64). Many poly[thio-l-(N,N-dialkyl-aminomethyl)ethylene]s are optically active, and in these cases ORD and CD techniques may be used to study their protonation behaviour, in addition to potentiometric techniques. 

Solvent e at S0"C />-Mcthoxy aniline /V./V-Dimethyl-p-phenylenediaminc 1,3-Bis(aminomethyl)benzenee ... 

When p-nitro-N,N-dimethylaniline (IVc) was ozonized at 0°C in ethyl acetate, methylene chloride, or methanol, a mixture of products resulted. In addition to the expected side-chain oxidation products— p-nitro-N-methylaniline (Vc), p-nitro-N-methyl formanilide (Vic)—a peroxide compound was formed. This peroxide, which is not formed until the solvents are removed, was shown by a series of experiments (described below) to be identical with di-[(N-methyl-p-nitrophenyl)-aminomethyl] peroxide (VII). Deoxygenation of VII with triethyl phosphite (7) yielded the ether VIII, which in turn decomposed at its melting point to the amine IX. 

Mojtahedi, M.M., Sharifi, A., Mohsenzadeh, R, and Saidi, M.R. 2000. Microwave-assisted aminomethylation of electron-rich componnds nnder solvent-free condition. Synthetic Communications, 30 69-72. 

Heterocyclic substrates, such as pyrrole and imidazole derivatives 68, may undergo selective Mannich reactions. C-Aminomethylation is favored by acidic conditions, whereas N-Mannich bases are produced when free amine and formaldehyde, or N,0-acetals in anhydrous solvents, are employed. Heterocyclic N-Mannich bases, however, are not particularly stable and may therefore behave as aminomethylation agents (see,... 

Besides the carbonyl, other residues, such as N-heteroaromatic rings bearing methyl or methylene groups, are also capable of activating the alkyl C—moieties of the substrate. Dimcthyl-nitrooxazinc 73 reacts only on the methyl group in the a position with respect to the O atom.- The triazole-benzodiazcpine 74 behaves similarly, and it has been found that mono- or bis-aminomethylation as well as aminomethylation of the methyl and the methylene group are notably affeeted by the type of solvent used and even by the order of the addition of reactants. 

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