Reactions of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-Alkenylanilines: VII. Synthesis of Indole Heterocycles from Products of Reaction between <Emphasis Type="Italic">N</Emphasis>-Mesyl-2-(1-alken-1-yl)anilines and Halogens

N-Mesyl-2-(1-methyl-1-butenyl)-6-methylaniline reacted with Br₂ to afford N-mesyl-2-(3-bromo-1-penten-2-yl)aniline that under treatment with NH₃ or amines underwent cyclization into N-mesyl-7-methyl-3-methylene-2-ethylindoline. The reaction of N-mesyl-2-(1-methyl-1-buten-1-yl)-4-methyl- and 2-(1-methyl-1-buten-1-yl)aniline with Br₂ gave rise to the corresponding N-mesyl-2-(2-bromo-1-methyl-1-buten-1-yl)anilines. Under the similar conditions N-tosyl-2-(1-cyclohexen-1-yl)aniline was converted into N-tosyl-2-(6-bromo-1-cyclohexen-1-yl)aniline that under treatment with NH₃ furnished N-tosyl-1,2,3,9a-tetrahydrocarbazole. The reaction of N-mesyl-1,2,3,9a-tetrahydrocarbazole with CuBr₂ in MeOH afforded N-mesyl-4-methoxy-1,2,3,4-tetrahydrocarbazole. N-Mesyl-6-methyl-2-(1-cyclopenten-1-yl)aniline in reaction with Br₂ in the presence of NaHCO₃ was oxidized into the corresponding cyclopentenone, and with NBS it gave N-mesyl-2-(2-bromo-1-cyclopenten-1-yl)aniline.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 730–737.Original Russian Text Copyright © 2005 by Gataullin, Sotnikov, Spirikhin, Abdrakhmanov.     

Synthesis and X-ray structures of cyclorhodated indole-tert-thiocarboxamides

Indole-1(and 3)-N,N-dimethylthiocarboxamide, 3-(1-pyrrolidinothiocarbonyl)indole and -1-methylindole (HL) react with hexachlorotetrakis(tri-n-butylphosphine)dirhodium(III) to give cyclorhodated complexes, [Rh(L)Cl₂(PBu₃)₂] with L acting as a C—S chelate ligand (PBu₃ = tri-n-butylphosphine) and indole-2-N,N-dimethylthiocarboxamide forms [Rh(L)Cl₂(PBu₃)₂] with L acting as an N—S chelate. 1-Methylindole-2-N,N-dimethylthiocarboxamide and 2-(1-pyrrolidinothiocarbonyl)-1-methylindole did, however, not react under similar conditions. The complexes were characterized by spectroscopic methods and the structures of the four complexes with HL = indole-1- and 3-N,N-dimethylthiocarboxamide, and 3-(1-pyrrolidinothiocarbonyl)indole and -1-methyl-indole were confirmed by X-ray analysis. The octahedral complex [Rh(L)Cl₂(PBu₃)₂] had trans-(PBu₃)₂ and cis-(Cl)₂ arrangements and L was coordinated through the S and indole ring C2 atoms to form a five-membered chelate ring. The unreactivity of 1-methylindole-2-N,N-dimethylthiocarboxamide and 2-(1-pyrrolidino)thiocarbonyl-1-methyl-indole may be due to steric hindrance caused by the additional 1-methyl substituent.     

Synthesis and spectral analysis of (±)-cis-N-[1-(2-hydroxy-2-phenyl-ethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide and (±)-cis-N-[1-(2-hydroxy-1-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide

Treatment of (±)-cis-N-(3-methyl-4-piperidyl)-N-phenylpropanamide (2) with styrene oxide (1) yielded a mixture of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (3) and (±)-cis-N-[1-(2-hydroxy-1-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (4) . The structure of compound 3 was confirmed by an unambiguous synthesis via (±)-cis-N-[1-(2-oxo-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (6) . The proton and carbon-13 resonances of compounds 3 and 4 were assigned with the aid of two-dimensional heteronuclear correlation experiments.     

Reaction of N1, N2-diarylamidines with chloranil and 2,3-dichloro-1,4-naphthoquinone

Nucleophilic attack by N² of N¹ N²-diarylformamides 1a-c on C-2 of chloranil (2) and subsequently by N¹ on C-1 of 2 initiates the formation of benzimidazolinones 8a-c. In contrast, when 1b-e is reacted with 2,3-dichloro-1,4-naphthoquinone (9) , both chlorine atoms are successively substituted by the two nitrogen atoms and 2-(arylamino)-3-(N-formylarylamino)-1,4-naphthoquinones 13b-e result, which (probably via their cyclic tautomers 12b-e ) may be cyclodehydrogenated to form N¹,N³-diarylnaphtho[2,3-d] imidazoline-2,4,9-triones (as 14b,c ). On the other hand, N¹,N²diarylacetamidines 15a-d attack 2 and 9 at C-2 with N² but subsequently exert nucleophilic character at the acetamidine α-carbon attacking C-1 of 2 and 9 , respectively, thus forming 1-aryl-2-(arylimino)-3a-hydroxy-2,3,3a,6-tetrahydro-1N-indol-6-ones 18a-d and 3-aryl-2-(arylimino)-9b-hydroxy-2,3,5,9b-tetrahydro-1-H-benz[e]indol-5-ones 19b,c , respectively. The latter may be thermally dehydrated to the fully conjugated 2,5-dihydro-3H-benz[e]indol-5-ones 20b,c. Unambiguous structural assignments for 18b and 20c are made on the basis of X-ray crystal structure analyses.     

Syntheses and X-ray crystal structures of five- and six-coordinate copper(II) complexes of N,N,N′,N′-tetraalkylpyridine-2,6-dicarboxamides containing–OClO3 and–OSO2CF3 counter ions

Reactions of anhydrous copper(II) chloride with NaX (1 : 1 or 1 : 2) and AgX (1 : 2) containing appropriate N,N,N′,N′-tetraalkylpyridine-2,6-dicarboxamides(O-daap) in CH₃CN yield monosubstituted five-coordinate [Cu(L₁)Cl(CF₃SO₃)] (1), [Cu(L₂)Cl(ClO₄)] (2), [Cu(L₃)Cl(ClO₄)] (3), and six-coordinate [Cu(L₂)(CF₃SO₃)₂] · H₂O (4) (X = ?OClO₃ and–OSO₂CF₃; L₁ = N,N,N′,N′-tetraethylpyridine-2,6-dicarboxamides; L₂ = N,N,N′,N′-tetraisopropylpyridine-2,6-dicarboxamides; L₃ = N,N,N′,N′-tetraisobutylpyridine-2,6-dicarboxamides). The structures of these complexes have been determined by X-ray crystallography. The Cu²⁺ in 1–3 adopts distorted square-pyramidal geometry, while 4 exhibits octahedral structure. Steric factors in conjunction with lattice effects and the nature of the anions are responsible for the variety in coordination spheres. These compounds undergo extensive intermolecular H-bonding to give to 2-D sheets extending along various planes.     

Synthesis and properties of 1-aryl-2-alkyl-1,4,5,6-tetrahydropyrimidines

A general method is described for the synthesis of 1-aryl-2-alkyl-1,4,5,6-tetrahydropyrimidines 1 , by cyclization of N-acyl-N′-aryltrimethylenediamines 2 with trimethylsilyl polyphosphate. Precursors 2 were obtained by aminolysis of the corresponding N-(3-bromopropyl)amides 3. The ¹H nmr spectra of tetrahydropyrimidines 1 are analyzed, discussing the influence of substituents in positions 1 and 2 of the heterocyclic ring. Alkaline hydrolysis of compounds 1 , which originates exclusively N-acyl-N′-aryltrimethylenediamines 2 , through an intermediate carbinolamine, was also studied. Cleavage of such an intermediate is discussed in the light of the stereoelectronic control theory. Reduction of compounds 1 with borane, leads regiospecifically to N-alkyl-N′-aryltrimethylenediamines 6.     

Competing processes in condensation of 3,3-bis(methylthio)-2-cyano-<Emphasis Type="Italic">N</Emphasis>-arylacrylamides with cyanoacetanilides

Reaction of cyanoacetanilides with 3,3-bis(methylthio)-2-cyano-N-arylacrylamides proceeds to form isomeric N,1-diaryl-1,6-dihydropyridine-3-carboxamides. A single crystal consisting of 2-amino-4-methylthio-N-(2-methoxyphenyl)-6-oxo-1-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide and 2-amino-4-methylthio-1-(2-methoxyphenyl)-6-oxo-N-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide was studied by XRD.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. X. Synthesis of N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones and of 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones

Cycloaddition of dichloroketene to N,N-disubstituted 1-amino-4-methyl-1-penten-3-ones and 1-amino-4,4-dimethyl-1-penten-3-ones occurred in moderate to fair yield only in the case of aromatic N-substitution to give N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones, which were dehydrochlorinated with DBN to afford in good yield N,N-disubstituted 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones. In the case of aliphatic N,N-disubstitution, cyclo-addition led directly to 6-alkyl-4-dialkylamino-3-chloro-2H-pyran-2-ones only for N,N-disubstituted 1-amino-4,4-dimethyl-1-penten-3-ones. The reaction between 1-dimethylamino-4-methyl-1-penten-3-one and dichloroketene gave 3-chloro-4-dimethylamino-3,6-dihydro-6-isopropylidene-2H-pyran-2-one in low yield.     

Synthesis and activity of four (N,N‐dimethylamino)benzamide nonsteroidal anti‐inflammatory drugs based on thiazole and thiazoline

Four compounds derived from 2‐aminothiazole and 2‐amino‐2‐thiazoline were prepared by coupling the respective bases with the acid chlorides of either 3‐ or 4‐(N,N‐dimethylamino)benzoic acid. Products were identified using infrared spectroscopy, ¹H NMR spectroscopy and electrospray mass spectroscopy and in two cases by single‐crystal X‐ray diffraction. Of the four, N‐(thiazol‐2‐yl)‐3‐(N,N‐dimethylamino)‐benzamide (1), N‐(thiazolin‐2‐yl)‐4‐(N,N‐dimethylamino)benzamide (2), N‐(thiazolin‐2‐yl)‐3‐(N,N‐dimethylamino) benzamide (3) and N‐(thiazolin‐2‐yl)‐4‐(N,N‐dimethylamino)benzamide (4), the hydrochloride salts of compounds 3 and 4 showed anti‐inflammatory activity across a concentration range of 10^?2?5 × 10^?4 M while 3 (at a concentration of 10^?5 M) was found to have no adverse effect on myocardial function. The X‐ray crystal structure of 2 and the 1:1 adduct structure of 3 with 3‐(N,N‐dimethylamino)benzoic acid are reported.     

New Synthetic Approach to 4-N-Arylaminoazuleno[2,1-d]pyrimides

1-Cyano-2-N,N-dimethylformamidinylazulenes as new synthons directed to heterocycle-fused azulenes were obtained by the condensation of 2-amino-1-cyanoazulenes and N,N-dimethylformamide dimethyl acetal (DMFDMA). 1-Cyano-2-N,N-dimethylformamidinylazulene (2a) and 1-bromo-3-cyano-2-N,N-dimethylformamidinylazulene (2b) reacted with anilines (3a–h) to give 4-N-arylaminoazuleno-[2,1-d]pyrimidines in moderate yields. This reaction provides a new procedure for synthesis of pyrimidine-fused azulenes.     

Synthesis and Characterization of Oxybis(Diacetoxyborane) Derivatives of Bifunctional Tridentate Aldimines

The reactions of oxybis(diacetoxyborane) with the aldimines, N-(2-hydroxyethyl) salicylaldimine N-(2-hydroxy-1-propyl) salicylaldimine, N-(3-hydroxy-1-propyl) salicylaldimine, N-(o-hydroxyphenyl) salicylaldimine. N-(m-hydroxyphenyl) salicylaldimine, N(2-hydroxyethyl)-2-hydroxy-1-naphthaldimine and N(2-hydroxy-1-propyl) 2-hydroxy-1-naphthaldimine have been carried out in 1: 1 and 1: 2 molar ratios. All the compounds except those derived from N-(3-hydroxy-1-propyl) salicylaldimine have been found to be sparingly soluble in benzene and nonelectrolytes in anhydrous DMF. The newly synthesized derivatives have been characterized by elemental analysis, molecular weight determinations and infrared, proton magnetic resonance, ultraviolet, visible and ¹¹B nuclear magnetic resonance spectral studies.     

On the behavior of α-brominated dimethyl o-benzenediacetate toward nitrogen nucleophiles. Part II. Reaction of dimethyl α-bromo-o-benzenediacetate with hydrazines

Dimethyl α-bromo-o-benzenediacetate ( 1 ) condensed with hydrazine and acetylhydrazine to give respectively 1-carbomethoxy-2-amino-1,4-dihydro-3-(2H)isoquinolinone (2) and its N-acetyl derivative ( 9 ). Replacement of the bromine atom of 1 with the N-1-methylhydrazino ( 3 ) and the N-1-phenylhydrazino ( 5 ) groups occurred by allowing 1 to react respectively with methylhydrazine and phenylhydrazine. In the latter case alkylation by 1 at the N-2 also occurred which led to the formation of the 2-phenylaminoisoquinolinone ( 8 ). Derivatives 3 and 5 smoothly cyclized to the 1-earbomethoxy-5(H)-1,2,3,4-tetrahydro-2,3-benzodiazepin-4-ones 4 and 6 . A series of derivatives of 2 were also pharmacologically tested as antiinflammatory and CNS depressant agents.     

Synthesis ofN-(3-azido-2-nitroxypropyl)-,N-(2,3-diazidopropyl)-, andN-(2-azido-3-methoxypropyl)-N-alkylnitramines

N-(3-Azido-2-nitroxypropyl)-N-alkylnitramines andN-(2,3-diazidopropyl)-N-alkylnitramines were prepared by nitration and azidation ofN-alkyl-N-(2-hydroxy-3-chloropropyl)sulfamates andN-(3-azido-2-hydroxypropyl)-N-alkylsulfamates. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 206–208, January, 1999.     

Dass Hydrierprodukt eines β-Nitro-N-nitrosoamins ist kein 1,2,3-Triazolidin,sondern ein β-Hydroxylamino-N-nitrosoamin

The Product of Hydrogenation of a β-Nitro-N-nitrosoamine Is Not a 1,2,3-Triazolidine, but a β-Hydroxylamino-N-nitrosoamine It is shown, by spectroscopy, that the product of catalytic hydrogenation of N, 2-dimethyl-2-nitro-N-nitrosopropylamine (1) consists of a 5:1 mixture of (E)- and (Z)-2-hydroxylamino-N, 2-dimethyl-N-nitrosopropylarnine (3) and does not contain - as had been claimed - any l, 2-dihydroxy-1, 2, 3-triazolidine (2). Thus there is still no evidence for the existence of the N(OH)N(OH) functionality. The structure of intermediates on the way to 1 are also revised.     

14H-Naphtho[1′,2′:5,6] pyrano[2,3-b]quinoline derivatives

Reaction of (N-alkyl-N-phenyl)ethoxycarbonylacetamides with β-naphthol in the presence of phosphorus oxychloride afforded 1-oxo-3-(N-alkyl-N-phenyl)amino-1H-naphtho[2,1-b]pyrans. These compounds underwent reaction with N,N-dimethylformamide-phosphorus oxychloride at 95° yielding a mixture of 14H-naphtho[1′,2′:5,6]pyrano[2,3-b]quinoline derivatives and 1-oxo-2-formyl-3-(N-alkyl-N-phenyl)amino-9-oxy-1H-phenalene. When the same reaction was performed at 140°, only 14-oxo-14H-naphtho[1′,2′:5,6]pyrano[2,3-b]quinoline was obtained in a very good yield. The structures of such compounds were demonstrated by spectral data and by chemical transformations. On the other hand, the expected formylation in the 2 position was achieved when 1-oxo-3-(N-alkyl-N-benzyl)amino-1H-naphtho[2,1-b]pyrans reacted with N,N-dimethylformamide-phosphorus oxychloride.     

Separation and identification of purine nucleosides in the urine of patients with malignant cancer by reverse phase liquid chromatography/electrospray tandem mass spectrometry

Urinary‐modified nucleosides have a potential role as cancer biomarkers for a number of malignant diseases. High performance liquid chromatography (HPLC) was combined with full‐scan mass spectrometry, MS/MS analysis and accurate mass measurements in order to identify purine nucleosides purified from urine. Potential purine nucleosides were assessed by their evident UV absorbance in the HPLC chromatogram and then further examined by the mass spectrometric techniques. In this manner, numerous modified purine nucleosides were identified in the urine samples from cancer patients including xanthine, adenosine, N1‐methyladenosine, 5′‐deoxy‐5′‐methylthioadenosine, 2‐methyladenosine, N6‐threonylcarbamoyladenosine, inosine, N1‐methylinosine, guanosine, N1‐methylguanosine, N7‐methylguanine, N2‐methylguanosine, N2,N2‐dimethyguanosine, N2,N2,N7‐trimethylguanosine. Furthermore, a number of novel purine nucleosides were tentatively identified via critical interpretation of the combined mass spectrometric data including N3‐methyladenosine, N7‐methyladenine, 5′‐dehydro‐2′‐deoxyinosine, N3‐methylguanine, O6‐methylguanosine, N1,N2,N7‐trimethylguanosine, N1‐methyl‐N2‐ethylguanosine and N7‐methyl‐N1‐ethylguanosine. Copyright © 2009 John Wiley & Sons, Ltd.     

Aminierende,reduktive Kupplung aromatischer Aldehyde mit Tris(dialkylamino)methylvanandium (IV) zu N,N,N′,N′-Tetraaalkyl-1,2-diaryläthylendiaminen

Aminative Reductive Coupling of Aromatic Aldehydes to N,N,N′,N′-Tetraalkyl-1,2-diarylethylenediamines, Induced by Tris(dialkylamino)methylvanadium (IV) In a novel type of reaction, certain aromatic aldehydes (benzaldehyde, p-methoxybenzaldehyde, 1-naphthaldehyde, furan-2-carbaldehyde) and secondary amines are coupled to give N,N,N′,N′-tetraalkyl-1,2-diarylethylenediamines 1–6 . The reagents are tris(dialkylamino)methylvanadium(IV) compounds (cf. Eqn. 2). These are generated in situ either from isolable chlorotris(dialkylamino) vanadium(IV) (Eqn. 3), or preferably, from an Et₂O/pentane solution of VCl₄ which is treated sequentially with 3 equiv. of lithium dialkylamide, 1 equiv. of MeLi, and 0.8 equiv. of an aromatic aldehyde, to give the products 1–6 in a one-pot preparation (Scheme 2). The yields range from 14 to 54%. The diastereoisomeric mixtures (meso- and (±)-forms) obtained are separated by chromatography (Al₂O₃, petroleum ether/Et₂O/Et₃N), and the pure stereoisomers fully characterized. A mechanism of the reductive coupling induced by CH₃V (NR₂)₃ is proposed (Scheme 1).     

1,2,3-thiadiazoles. I. Synthesis of sodium (or potassium) 1,2,3-thiadiazole-4-thiolates via thiocarbazonate esters and N-acylthiohydrazonate esters

A general synthesis of 1,2,3-thiadiazole-4-thiolates 1 and their derivatives 2–3 by an extension of the Hurd-Mori 1,2,3-thiadiazole synthesis is described. Treatment of methyl (or ethyl) [1-(alkylthio)alkylidene]hydrazinocarboxylates 11 (thiocarbazonate esters) or other N-acylthiohydrazonate esters [Y = ureido ( 12 ) or arenesulfonyl ( 13 )] with thionyl chloride affords 2–3 efficiently. Intermediates 11–13 are readily obtained from the N²-thioacylcarbazates 8 , N³-thioacylsemicarbazides 9 , or N²-thioacyl-N¹-(p-toluenesulfonyl)hydrazides 10 , respectively, by S-alkylation. Physicochemical properties of the 1,2,3-thiadiazoles 1–3 and N-acylthiohydrazonate esters 11–13 are also described.     

Reactions of 2-amino-, 2-alkylamino-, and 2-piperidino-1-azaazulenes with aryl and chlorosulfonyl isocyanates

Reaction of 2-amino-1-azaazulene with phenyl isocyanate gave 3-phenyl-2H-3,4-dihydro-1,3,4a-triazabenz[5,4-a]azulene-2,4-dione. Reactions of 2-alkylamino-1-azaazulenes with aryl isocyanates gave 2-(N-ethyl-N′-arylureido)-1-azaazulenes initially, which rearranged to N-aryl-2-alkylamino-1-azaazulene-3-carboxamides and successive reaction with another molar amount of aryl isocyanate furnished uracil-fuzed 1-azaazulenes. Reaction of 2-piperidino-1-azaazulene with aryl isocyanate gave N-aryl-2-piperidino-1-azaazulene-3-carboxamide. Reaction of 2-(substituted amino)-1-azaazulenes with chlorosulfonyl isocyanate gave 3-cyano- and 3-chloro-2-(substituted amino)-1-azaazulenes.     

On the synthesis and isolation of chlorocarbazoles obtained by chlorination of N-substituted carbazoles

Chloro derivatives of N-methylcarbazole ( 1 ), N-phenylcarbazole ( 2 ), N-acetylcarbazole ( 3 ), N-benzoylcarbazole ( 4 ) and 2-methoxy-N-methylcarbazole are synthesized. They are compounds 1a, 1b, 1c, 1d, 1e, 2a, 2b, 3a, 3b, 3c, 3d, 4a, 4b, 5a, 5b, 5c, 5d and 5e . Some of them are described for the first time. By using semiempirical PM3 method theoretical substituent effects on the chlorinating reaction are calculated. A chlorination mechanism of carbazoles and N-substituted carbazoles are compared.