Methylammonium Acetate Research Articles

The synthesis of 5-ylidenepyrrol-2(5H)-ones from maleimides and from pyrrol-2-(5H)-ones

A series of maleimides 5 have been prepared by reaction of the appropriate maleic anhydrides with either ammonium acetate or methylammonium acetate in boiling acetic acid. The maleimides underwent Wittig-type reactions with stabilised phosphoranes, under moderately forcing conditions, to give 5-ylidenepyrrol-2(5H)-ones 6. The ease of the reaction and the regiochemistry of the addition to unsymmetrical maleimides depended upon the nature of the 3-substituent and on the presence or absence of an N-alkyl substituent. Thus, 3- methoxymaleim ides reacted exclusively at C-2; the presence of an N-methyl substituent required the use of more forcing reaction conditions, but did not alter the preference for C-2 attack. With 3-methylmaleimides, however, the slight preference for reaction at C-2 in 5c was overturned by the presence of an N-methyl substituent as in 5d. The related reactions of unstabilised phosphoranes or phosphine oxides usually only afforded intractable gums, and with Julia-type reagents only starting materials were recovered. However, the lithium enolate of methyl trimethylsilylacetate (or other Peterson-type reagents) underwent successful addition to N-methylmaleimides at –78 °C; the 5-ylidenepyrrolone product distributions were similar to those obtained with the stabilised phosphoranes. Variation of the 5-alkylidene side-chain was achieved through the reactions of N-methylmaleimides with alkyl Grignard reagents by dehydrating-the first-formed 5-alkyl-5-hydroxypyrtolone. 4-Methoxy-1-methylpyrrol-2(5H)-one could be deprotonated exclusively at the 5-position under kinetic control (i.e. BuLi, THF, –78 °C), and the anion then quenched with a variety of electrophilic agents to give 5-substituted pyrrolones. These derivatives proved amenable to dehydration or dehydrogenation, as appropriate, to afford the corresponding 5-alkylidenepyrrolones.

The use of two different buffers for unequivocal molecular weight determination in liquid chromatography/thermospray mass spectrometry

AbstractHigh‐performance liquid chromatography (HPLC) in combination with thermospray mass spectrometry (LC/TSP‐MS) is an important method for molecular weight determination of unknown compounds. In addition to the well‐known ammonium acetate buffer (NH4OAc) the use of methylammonium acetate (CH3NH3OAc) in the positive‐ and ammonium formate (NH4OFo) in the negative‐ion mode is recommended. Performing a second run with these buffers, even from spectra with only one single quasimolecular ion, an unequivocal molecular weight can be obtained. For correct assignment, the shift in mass of the corresponding quasimolecular ions in each mode is used. Finally, the use of a second buffer greatly facilitates the recognition of superimposed HPLC peaks.

ChemInform Abstract: Condensation of Salicylaldehyde with Phenylacetone and Ammonia.

AbstractThe reaction between salicylaldehyde (I), benzyl methyl ketone (II) and ammonium acetate (III) yields the products (IV)‐(VI).

High-performance liquid chromatographic method for determining trichothecene mycotoxins by post-column fluorescence derivatization

The method described here is based on a separation of deoxynivalenol, nivalenol and fusarenon-X on a C 18 column using aqueous acetonitrile, and successive post-column fluorescence derivatization involving an alkaline decomposition to form formaldehyde and modified Hantzsch reaction with methyl acetoacetate and ammonium acetate (λ ex = 370 nm and λ em = 460 nm). By this method, 5–10 ng of the standard trichothecenes could be determined. By employing a clean-up procedure with a florisil column and a Sep-Pak CN cartridge, 61.4–96.9% recoveries were obtained for deoxynivalenol and nivalenol added to corn, wheat and barley at concentration levels of 0.05–1 ppm.

Fluorescent and photoactivatable fluorescent derivatives of tetrodotoxin to probe the sodium channel of excitable membranes.

Fluorescent and photoactivatable fluorescent derivatives of tetrodotoxin (TTX) have been synthesized. N-Methylanthraniloylglycine hydrazide, anthraniloyl hydrazide, and 2-azidoanthraniloylglycine hydrazide were coupled to the carbonyl at C6 of oxidized tetrodotoxin to form stable fluorescent hydrazones. The C6 ketone can be reductively aminated with either ammonium or methylammonium acetate to form 6-amino- or 6-(methylamino)tetrodotoxin, which can then be acylated by a variety of fluorescent reagents. The biological activity, competitive binding with [3H]tetrodotoxin for the receptor on rat axonal membranes, and equilibrium binding isotherms obtained by fluorescence enhancement or anisotropy indicate that the derivatives are only about 2-5 times less active then tetrodotoxin itself. The 2-azidoanthraniloylglycine hydrazone of oxidized tetrodotoxin, when activated by light, generates a reactive nitrene which is capable of covalent insertion into the toxin receptor. The product of the photolysis is a highly fluorescent tetrodotoxin derivative which is irreversibly linked to the receptor site. The excitation and emission spectra of the fluorescent tetrodotoxin derivatives vary with solvent polarity, and this sensitivity has been used to determine the immediate environmental characteristics of the toxin binding site of the sodium channel. It is concluded that the toxin binding site is highly polar. Emission and excitation spectra reveal that radiationless energy is transferred from tryptophan residues of the receptor to the anthraniloyl group of the TTX derivatives.

A new synthesis of 1,4-dihydropyridines

The synthesis of 1,4-dihydropyridines unsubstituted in the 1-, 2-, and 6-positions from methyl propiolate, aromatic aldehydes, and ammonium acetate in acetic acid is described. The products were oxidised to the corresponding pyridines. Certain features of their n.m.r. spectra are discussed.

Pteridine studies. XLI. New routes to 4-aminopteridines via 3-(dimethylaminomethyleneamino)pyrazine-2-carbonitrile and related compounds.

3-Aminopyrazine-2-carboxamide was converted into 3-(dimethylaminomethyleneamino)pyrazine-2-carbonitrile (1b) with dimethylformamide and phosphoryl chloride. This amidine (1b) was produced by the same reagents also from 3-aminopyrazine-2-carbonitrile (1a), and by the action of dimethylamine on 3-ethoxymethyleneamino-pyrazine-2-carbonitrile (1c). Compound (1c) was made from 3-aminopyrazine-2-carbonitrile with triethyl orthoformate and acetic anhydride.Compounds (1a—c) were used in several new pteridine syntheses. The amidine (1b) gave 4-amino- and 4-methyl-amino-pteridine (2a and b) with ammonium and methylammonium acetate, respectively. Use of the 6-chloro-derivative of amidine (1b) similarly led to 6-chloro-4-amino- and -4-methylamino-pteridine. Pteridine-4-thione was obtained from the amidine (1b) and sodium hydrosulphide. The ethoxymethylene compound (1c) gave 4-aminopteridine with ammonia but 3,4-dihydro-4-imino-3-methylpteridine (3) with cold methylamine; this imine was easily isomerized to 4-methylaminopteridine by a Dimroth reaction, but proved stable as a solid. 3-Aminopyrazine-2-carbonitrile (1a) gave 4-aminopteridine with formamidine acetate at 140°.Some unusual pyrazine reactions were encountered. The ethoxymethylene compound (1c), after brief contact with ammonium acetate solution, gave 3-(aminomethyleneamino)pyrazine-2-carbonitrile (1e). The ethoxy-methylene compound (1c) was hydrolysed by the water in cold 95% ethanol to 3-formamidopyrazine-2-carbonitrile (1d), and condensed with hydrazine hydrate to give 3-hydrazinomethyleneaminopyrazine-2-carboxamidrazone (4b). 3-Aminopyrazine-2-carbonitrile (1a) similarly gave 3-aminopyrazine-2-carboxamidrazone (4a). 3-Aminopyrazine-2-carboxamide was quantitatively brominated to give 3-amino-6-bromopyrazine-2-carboxamide.