PHOSPHORUS-NITROGEN COMPOUNDS. PART 52.1 THE SYNTHESIS OF SOME 1,3,2-BENZODIAZAPHOSPHORINE 2-OXIDES AND 2-SULPHIDES

Abstract

The reactions of 4-methyl-2-[N-(p-toluidinyl)methyl]aniline with phosphorus oxychloride, thiophosphoryl chloride, and their derivatives yield 1,3,2-benzodiazaphosphorine 2-oxides and 2-sulphides. Their ¹H NMR and infrared spectra are discussed. Related 1,3,2-benzodiazophosphorine and 1,3,2-dibenzodiazaphosphocine 2-oxides and 2-sulphides are compared.     

Stable nitroxide radicals. Reaction between 2-cyano- and 4-cyanobenzoquinoline N-oxides and the grignard reagent

2,2-Diphenylbenzoquinolinenitroxide radicals were obtained starting from 2-phenyl-, 2-cyano, 4-cyano-benzoquinoline N-oxides, or from unsubstituted benzoquinoline N-oxides with phenylmagnesium bromide. The elimination of bromomagnesium hydride from the 2-unsubstituted benzoquinoline N-oxides and cyanomagnesium bromide from the 2- or 4-cyanobenzoquinoline N-oxides is discussed.     

Furopyridines. XXVII. Reactions of 2-methyl and 2-cyano derivatives of furo[2,3-b]-, -[3,2-b]-, - [2,3-c]- and -[3,2-c]pyridine

Bromination of 2-methylfuropyridines 1a-d-Me gave the 3-bromo derivatives 2a-d , while the 2-cyano compounds 1a-d-CN resulted in the recovery of the starting compounds. Nitration of 1a-d-Me and 1a-d-CN did not yield the corresponding nitro derivative, except for 1-c-CN giving 3-nitro derivative 3c in 7% yield. N-Oxidation of 1a-d-Me and 1b-d-CN with m-chloroperbenzoic acid yielded the N-oxides 4a-d-Me and 4b-d-CN , whereas 1a-CN did not afford the N-oxide. Cyanation of N-oxides 4a-d-Me and 4b-d-CN with trimethylsilyl cyanide gave the corresponding α-cyanopyridine compounds 5a-d-Me and 5b-d-CN . Chlorination of 4a-d-Me and 4b-d-CN with phosphorus oxychloride also gave the α-chloropyridine compounds 6b-d-Me and 6b-d-CN , accompanying formation of γ-chloropyridine 6a-Me, 6′b-Me and 6′b-CN , β-chloropyridine 6′b-CN , and α'-chloropyridine derivatives 6′c-Me and 6′c-CN . Acetoxylation of 4a-d-Me and 4b-d-CN with acetic anhydride yielded α-acetoxypyridine compounds 7a-Me and 7b-CN , pyridone compounds 11d-Me, 11c-CN and 11d-CN , 3-acetoxy compounds 8, 9b, 9c , and 2-acetoxymethyl derivatives 10b and 10c.     

Polycyclic N-hetero compounds. XXII Reaction of pyridine N-oxides and Pyrazine di-N-oxides with formamide

Reactions of pyridine N-oxides, pyrazine di-N-oxides, and their benzologues with formamide are described. Carbamoylation mainly occurred at aromatic ring with loss of the N-oxide oxygen atom, however, 2,4,6-trimethylpyridine 1-oxide gave 2- and 4-pyrimidinyl derivatives.     

RuO<Subscript>4</Subscript>-mediated oxidation of<Emphasis Type="Italic">N</Emphasis>-benzylated tertiary amines. Are amine<Emphasis Type="Italic">N</Emphasis>-oxides and iminium cations reaction intermediates?

N-Benzylmorpholine,-piperidine, and-pyrrolidine (1A-C, resp.) are oxidised by RuO₄ (generated in situ) at both endocyclic and exocyclic (benzylic) N—α-methylene positions to afford lactams (and dioxo-derivatives) and benzaldehyde (and benzoyl derivatives), respectively. The N-oxides of 1A-C, formed by a minor side reaction, are not involved as intermediates. Control experiments showed the transient formation of endo- and exocyclic iminium cations trapped with NaCN as the corresponding nitriles. The proposed course of the RuO₄-mediated oxidation of 1A-C involves the consecutive steps 1⇒iminium cations+cyclic enamine⇒oxidation products. The endocyclic/exocyclic regioselectivity of the oxidation reaction lies between 0.8 (for 1A) and 2.1 (for 1B). The amine cation radical and the N-α-C· carbon-centered radical seem not to be involved.     

Oxidative cyclization of some 1,3-dioximes with lead tetraacetate

Oxidation of 1,3-dioximes 1 with lead tetraacetate gives di-N-oxides of pyrazolines 4 or pyrazoles 5 or N-oxides of oxadiazines 7 as the main reaction products. The reaction mechanism is discussed.     

Quinoline nitroxide radicals. Ipso-attack in the reaction between 2-methoxy and 2-cyanoquinoline N-oxide,and phenylmagnesium bromide

2-Methoxy and 2-cyanoquinoline N-oxide, when treated with phenylmagnesium bromide, undergo a nucleophilic ipso-attack at C-2, yielding, by elimination of methoxymagnesium bromide or cyanomagnesium bromide, the corresponding 2-phenylquinoline N-oxides, which react with the excess of Grignard reagents forming 2,2-diphenylquinoline 1-oxyls. Even when the methoxy and cyano groups are in position 4, the attack by the Grignard reagent takes place at C-2 giving 2-phenylquinolines and 2-phenylquinoline N-oxides by elimination of hydroxymagnesium bromide and bromomagnesium hydride, respectively; the formation of 2,2-diphenylquinoline l-oxyls in these reactions is discussed.     

Pyrimidine N-oxides. Oxidation of 5-nitroso-2,4,6-triaminopyrimidine

The peroxytrifluoroacetic acid oxidation of 5-nitroso-2,4,6-triaminopyrimidine ( 1b ) led to the formation of two products: 5-nitro-2,4,6-triaminopyrimidine 1-N-oxide ( 2 ) and 5-nitro-2,4,6-triaminopyrimidine 1-3-di-N-oxide ( 3 ). On the basis of previous experience 2 was the sole expected oxidation product. However, 3 represents a rather unexpected development in that di-N-oxides in the pyrimidine series are uncommon. The yields are good for both products and structures are assigned on the basis of elemental analysis, mass spectral data, and chemical reactions. The reaction sequence is also discussed.     

Synthesis and oxidation of 1-hydroxy-3(2)-imidazoline-derived enaminones

Interaction of 1-hydroxy-3-imidazoline and 3-imidazoline 3-oxide derivatives with esters in the presence of LDA gives enaminones, derivatives of imidazolidine. Oxidation of these compounds with MnO₂ leads to4H-imidazoleN-oxides, oxidative dirnerization products, or stable nitroxyl radicals, depending on the structure of the initial compound.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1789–1795, July, 1996.     

New β-amino-α-trifluoromethyl alcohols and their exploration in the synthesis of trifluoromethylated imidazole derivatives

Racemic and enantiomerically pure β-amino-α-trifluoromethyl alcohols were obtained via sequential nucleophilic trifluoromethylation of selected α-imino ketones, derived from arylglyoxals, and subsequent removal of the MeO or Ph(Me)CH substituent, respectively, located at the N-atom. The obtained products, containing a primary amino group, were used for the synthesis of imidazole N-oxides bearing a trifluoromethyl group as a part of the N(1)-alkyl chain. Imidazole N-oxides with an electron-withdrawing ester group at C(4) underwent spontaneous isomerization under the reaction conditions, and the corresponding imidazol-2-ones derivatives were isolated as final products.     

Syntheses based on anabasine. Preparation and transformations of N-oxides

The oxidation of N-acetyl-and N-benzoylanabasine with the tert-butyl hydroperoxide (TBHP)— MoCl₅ system or MCPBA proceeds selectively at the nitrogen atom of the pyridine ring. The oxidation of N-methylanabasine under similar conditions gives a mixture of stereo-isomeric N-oxides at the piperidine nitrogen atom, their ratio depending on the reagent used. The oxidation of anabasine by TBHP— MoCl₅ or MCPBA is accompanied by dehydrogenation and results in anabaseine N-oxide. The reactions of anabasine and anabaseine pyridine N-oxides with acetic anhydride were investigated. The substituted 1H-3-pyridin-2-ones were prepared. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 322—328, February, 2006.     

Fused 1,2-dithioles. IV. Synthesis and reactions of 1,2-dithiole s-oxides

1,2-Dithiolopyrrolones and their heterologues of type 1 are resonance stabilized systems displaying a high dipole moment. Upon oxidation with organic peracids compounds 2 , 5 , 15a, 16a, 20a and 25a gave the corresponding S(2)-oxides and, depending on substituents, in some cases the S(2)- and S(1)-dioxides. The S(2)-monoxides showed a proclivity to disproportionation and were easily reduced to dithioles with symme trical dimethylhydrazine. From S(2)-oxides and several primary amines bicyclic isothiazole-S-oxides were obtained (S/N-exchange reaction). From the N-unsubstituted isothiazole S-oxide 10e the N-hydroxyisothiazole 9d was synthesized by an aza-Pummerer-type rearrangement. The assumption is made that S(2)-oxides may be biologically important as active metabolites of pyrrothines and analogues of type 1 in their action as antibacterials and antimycobacterials.     

2H-3,1-benzoxazine-2,4-(1H)-dione (isatoic anhydride). 15. Reactions with lactone enolates

The reaction of N-methylisatoic anhydride, 1 , with the lithium enolates derived from various butyrolactones or δ-valerolactone produces stable anthranoyl lactone derivatives 4 . Heating these products in toluene results in a cyclization to afford 4-hydroxy-3-(2-hydroxyalkyl)-1-methyl-2(1H)-quinolinones, 8 and 14 , in good yields.     

Direct arylation of azine N-oxides with aryl triflates

Palladium catalyzed direct arylation of azine N-oxides using aryl triflates to afford the corresponding 2-aryl azine N-oxides is described. The reaction is carried out with a range of both N-oxides and aryl triflates. The arylation can be carried out in sequence to yield differentially diarylated products. The regioselectivity and scope of 3-substituted azine N-oxides are investigated. The method is applied to the synthesis of a compound that exhibits antimalarial and antimicrobial activities.     

1,8-Naphthyridines. Part I. Synthesis of some trifluoromethyl-1,8-naphthyridine derivatives

The synthesis of some 2-amino-1,8-naphthyridine derivatives substituted in the 5- and/or 7-positions with trifluoromethyl is described along with their conversions to the corresponding 1,8-naphthyridin-2(1H)ones. A modified procedure for oxidizing electron-deficient heterocyclic compounds to their N-oxides is presented.     

Azomalonate Syntheses Part II. Synthesis and Reactivity of Novel 1,2,4-Triazin-5-one Derivatives

Base treatment of azomalonates derived from N-substituted dialkyl (2-chloroacetamido)malonates results in the formation of 4-substituted alkyl 5-oxo-1,4,5,6-tetrahydro-1,2,4-triazine-3-carboxylates. The same malonates coupled with diazotized 2-amino-5-chlorobenzophenone or methyl anthranilate afford triazinones which can be cyclized into novel triazino[1,6-a]indoles. Two representative heterocycles are further characterized by typical reactions. Whereas oxidation gives the corresponding triazine-5,6-diones, the outcome of the reduction is strongly dependent on the nature of the substituent at C(4). Bromination followed by aqueous workup leads to the 6-hydroxy derivatives. Some mechanistic aspects of this novel triazinone synthesis are discussed.     

Cross-coupling reaction of chloropyrazines with ethylenes

Various chloropyrazines and their N-oxides were submitted to the cross-coupling reaction with ethylenes, such as styrene, ethyl acrylate and acrylonitrile. While the chloro-phenylpyrazines and 2-chloropyrazine 1-oxides were slugglish in this reaction system, the expected products were obtained from almost all the 2-chloro-3,6-dialkylpyrazines and their 4-oxides in moderate to good yields.     

Studies on 5-arylidene-3-phenyl-2-methylmercaptohydantoins

The action of ammonium acetate on 5-arylidene-3-phenyl-2-methylmercaptohydantoins 1g,h in acetic acid led to the formation of the 5-arylidene-3-phenylhydantoin derivatives 4a,b . In absence of a solvent, ring opening and rearrangement took place with the formation of the 5-arylidene-N²-phenylglycocyamidine derivatives 7a-c . Compounds 7a-c reacted with methyl iodide to afford the corresponding 3-methyl derivatives 9a-c . The structures of the synthesised products were established and the mechanism proposed for the rearrangement reaction was discussed.     

Reactions of α-pentafluorophenylpyrylium salts with hydroxylamine

The reactions of α-pentafluorophenylpyrylium salts with hydroxylamine in ethanol afford isoxazoline derivatives and/or pyridine N-oxides depending on the steric characteristics of the substituent in the second α position. The structure of 2-hydroxy-2-pentafluorophenyl-4-phenyl-2,3,5,6,7,8-hexahydroquinoline 1-oxide, which was synthesized by the reaction of 2-pentafluorophenyl-4-phenyl-5,6,7,8-tetrahydrobenzopyrylium perchlorate with NH₂OH, was established by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 402–407, February, 2008.     

SPIONs as a nanomagnetic catalyst for the synthesis and anti-microbial activity of 2-aminothiazoles derivatives

A series of aminothiazole derivatives have been synthesized by using ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs) nanomagnetic catalysis, which were prepared by reducing the Fe(II) and Fe(III) precursors using aqueous ammonia then characterized by the XRD, FTIR, SEM, and TEM. The 2-aminothiazole derivatives were obtained by coupling 2-aminothiazole diazonium salt with active methylene compounds then cyclization with hydrazine hydrate to afford pyrazolyl derivatives. The one-pot reaction of 2-aminothiazole with an aromatic aldehydes in the presence of Fe₃O₄ NPs to give Schiff bases derivatives. An efficient protocol is developed proudest yields and reduction reaction time and easy separation. Therefore, all synthesized compounds were evaluated for anti-microbial activity.