Synthesis of 4(3H)-quinazolinones from derivatives of methyl 2-isothiocyanatobenzoate

Ethyl N-(2-methoxycarbonylphenyl)thiocarbamate ( 2), N -(2-ethoxycarbonylphenyl)-4-methoxythiobenz-amide ( 3b ), and 2-(4-methoxyphenyl)-4H-3,1-benzothiazin-4-one ( 4a ), react with nucleophilic reagents containing at least one primary amino group to yield a variety of 2-substituted and 2,4-disubstituted 4(3H)quinazolinones, as well as some tricyclic and tetracyclic products.     

A Reaction‐Based Fluorescent Probe for Imaging of Native Hypochlorous Acid

Hypochlorous acid (HOCl), one of the reactive oxygen species (ROS), is highly reactive and short‐lived. It is a challenge to dynamic monitor HOCl activity in living systems. Hence, we synthesized a new fluoresce nt probe RF1 based on protection of the hydroxyl group by N,N‐dimethylthiocarbamate recognition group, which reached a low fluorescence background signal and highly sensitive property. On account of the electrophilic addition of Cl⁺ to the sulfide of thiocarbamate moiety, probe RF1 was converted to resorufin and triggered emitting bright. RF1 showed not only the highly sensitive and selective response to HOCl in vitro, but also can be applied in environmental water samples and detected HOCl by test strips. Besides, the ability of RF1 monitoring HOCl in HeLa cells by exogenous simulation and tracing native HOCl in macrophages cells were also explored.     

4-(<Emphasis Type="Italic">N,N</Emphasis>-Dialkylthiocarbamoylthio)-5-nitropyrimidines as new potential nitric oxide donors

On heating at pH 6.86, 4-(N,N-dialkylthiocarbamoylthio)-5-nitropyrimidines are transformed into dithiolopyrimidines, which are either oxidized to bis(4-dialkylthiocarbamoylpyrimidin-5-yl) disulfides or converted into 4,6-diamino-5-nitropyrimidine derivatives with carbon disulfide elimination. The direction of the reaction is determined by the nature of a substituent in position 2 of pyrimidine and the bulk of the thiocarbamate substituent. Mechanistic schemes for these processes were proposed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2777–2783, December, 2005.     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. IX. Routes to substituted oxazolidin-2-ones and oxazolidine-2-thiones

4-Chlorobenzenesulfonyl isocyanate (I) reacted with 2-chloroethanol and 1-chloro-2-propanol to give, respectively, 2-chloroethyl 4-chlorobenzenesulfonyl carbamate (III) and 1-chloro-2-propyl 4-chlorobenzenesulfonyl carbamate (VI). The carbamates III and VI cyclized under the influence of pyridine to afford, respectively, 3-(4-chlorobenzenesulfonyl)oxazolidin-2-one (IV) and 3-(4-chlorobenzenesulfonyl)-5-methyloxazolidin-2-one (VII). The oxazolidin-2-ones were stable toward hydrochloric acid but hydrolyzed in 2M sodium hydroxide solution to N-(2-hydroxyethyl)-4-chlorobenzenesulfonamide (V) and N-(2-hydroxy-1-propyl)-4-chlorobenzene-sulfonamide (VIII), respectively. 4-Toluenesulfonyl isothiocyanate (II) reacted with 2-chloroethanol to give 2-chloroethyl 4-chlorobenzenesulfonyl thiocarbamate (IX), which was converted by pyridine to 3-(4-toluenesulfonyl)oxazolidine-2-thione (X).     

Synthesis of 5-Alkyl(aryl)-2-alkylsulfanyl(alkoxy)-4-hydroxy-6H-1,3-oxazin-6-ones

Alkyl carbamates and S-alkyl thiocarbamates react with substituted malonyl dichlorides in boiling benzene to give the corresponding 2,5-substituted 4-hydroxy-6H-1,3-oxazin-6-ones. The reaction of S-methyl thiocarbamate with unsubstituted malonyl dichloride in boiling diethyl ether or benzene leads to formation of S-methyl (3-methylsulfanylaminocarbonyl-3-oxopropionyl)thiocarbamate and is not accompanied by cyclization, whereas in boiling toluene 4-hydroxy-2-methylsulfanyl-6H-1,3-oxazin-6-one is obtained.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005, pp. 468–472.Original Russian Text Copyright © 2005 by Lalaev, Yakovlev, Zakhs.     

Synthesis and mechanism of formation of novel 2,5-dihydro-2,5-diimino-3,4-di[(N,N-dimethylamino)methylideneamino]pyrroles and 5-amino-3,4-di[(N,N-dimethylamino)methylideneamino]-2H-2-iminopyrroles

Formation of 5-amino-3,4-di[(N,N-dimethylarnino)methylidenearnino]-2H-2-iminopyrroles 3 from the reaction of (Z)-N¹-(2-amino-1,2-dicyanovinyl)-N²-substituted-formamidines 1 with dimethylformamide diethyl acetal has been shown to occur by initial formation of (Z)-N¹-{l,2-dicyano-2-[N,N-dimethylamino)methylideneamino]vinyl}formamidines 8 (isolated), followed by base catalysed cyclisation and imi dazole ring opening by dimethyl amine. The kinetic product of the ring opening reaction is the 2,5-diimino2,5-dihydropyrrole derivatives 11, which have been isolated and characterized spectroscopically and by a single crystal X-ray analysis on the R = Ph derivative. In solution at room temperature the N-aryl derivatives undergo a rapid Dimroth rearrangement to give the thermodynamic ally more stable isomer 3 , but compound 11 (R = Me) is much more stable in solution.     

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.     

Synthesis, structure, and spatial arrangement of Si-substituted N-(dimethylsilylmethyl)imides

The synthesis of N-(chlorodimethylsilylmethyl)succinimide and N-(chlorodimethylsilylmethyl)-glutarimide by the reaction of the corresponding N-trimethylsilylimides with chlorodimethylsilane and by the reaction of unsubstituted imides with a mixture of hexamethyldisilazane with dimethylchloromethylchlorosilane is described. The formation of N-(chlorodimethylsilylmethyl)succinimide is followed by substitution by the silicon atom, which, depending on the reagent ratio, provides N-(dimethylsuccinimidomethyl)succinimide as the major or minor product. ¹H, ¹³C, and ²⁹Si NMR spectroscopy and X-ray diffraction analysis showed that the silicon atom in N-(chlorodimethylsilylmethyl)glutarimide is five-coordinate. By contrast, in N-(chlorodimethylsilylmethyl)succinimide and N-(dimethylsuccinimidomethyl)succinimide, according to NMR and X-ray diffraction data, the silicon atom is four-coordinate. Quantumchemical calculations by the AM1 method show that the molecular conformations of N-(chlorodimethylsilylmethyl)imides containing an intramolecular OSi bond are not energetically most favorable in the gas phase.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 10, 2004, pp. 1617–1623.Original Russian Text Copyright © 2004 by Pogozhikh, Ovchinnikov, Kramarova, Negrebetskii, Shipov, Albanov, Voronkov, Pestunovich, Baukov.This revised version was published online in April 2005 with a corrected cover date.     

Mono- and dinuclear Zn(II) complexes of Schiff-base ligands: syntheses,characterization and studies of photoluminescence

Six Schiff-bases HL¹-HL⁴, L⁵ and L⁶ [HL¹ = 2,6-bis[1-(2-aminoethyl)pyrolidine-iminomethyl]-4-methyl-phenol, HL² = 2,6-bis[1-(2-aminoethyl)piperidine-iminomethyl]-4-methyl-phenol, HL³ = N-{1-(2-aminoethyl)pyrolidine}salicylideneimine, HL⁴ = N-{1-(2-aminoethyl)piperidine}salicylideneimine, L⁵ = 2-benzoyl pyridine-N-{1-(2-aminoethyl)pyrolidine}, L⁶ = 2-benzoylpyridine-N-{1-(2-aminoethyl)piperidine}] have been synthesized and characterized. Zn(II) complexes of those ligands have been prepared by conventional sequential route as well as by template synthesis. The same complexes are obtained from the two routes as evident from routine physicochemical characterizations. All the Schiff-bases exhibit photoluminescence originating from intraligand (π–π*) transitions. Metal mediated fluorescence enhancement is observed on complexation of HL¹-HL⁴ with Zn(II), whereas metal mediated fluorescence quenching occurs in Zn(II) complexes of L⁵ and L⁶.     

8-Aza-2′-deoxyguanosine and Related 1,2,3-Triazolo[4,5-d]pyrimidine 2′-Deoxyribofuranosides

The synthesis of 8-azaguanine N⁹-, N⁸-, and N⁷-(2′-deoxyribonucleosides) 1–3 , related to 2′-deoxyguanosine ( 4 ), is described. Glycosylation of the anion of 5-amino-7-methoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine ( 5 ) with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 6 ) afforded the regioisomeric glycosylation products 7a/7b, 8a/8b , and 9 (Scheme 1) which were detoluoylated to give 10a, 10b, 11a, 11b , and 12a . The anomeric configuration as well as the position of glycosylation were determined by combination of UV, ¹³C-NMR, and ¹H-NMR NOE-difference spectroscopy. The 2-amino-8-aza-2′-deoxyadenosine ( 13 ), obtained from 7a , was deaminated by adenosine deaminase to yield 8-aza-2′-deoxyguanosine ( 1 ), whereas the N⁷- and N⁸-regioisomers were no substrates of the enzyme. The N-glycosylic bond of compound 1 (0.1 N HCl) is ca. 10 times more stable than that of 2′-deoxyguanosine ( 4 ).     

Synthesis, X-Ray Diffraction Data, and 1H and 13C NMR Spectra of N-(N-Arylsulfonylimidoyl)-1,4-benzoquinonimines Derived from N-Aroyl(acetyl)-1,4-benzoquinonimines

Oxidation of N-(N-arylsulfonylimidoyl)-4-aminophenols gave the corresponding N-[N-arylsulfonylimidoyl)-1,4-benzoquinonimines, derivatives of N-aroyl- and N-acetyl-1,4-benzoquinonimines. The structure of the products was studied by the X-ray diffraction method and ¹H and ¹³C NMR spectroscopy. N-(N-Arylsulfonylimidoyl)-1,4-benzoquinonimines were found to undergo fast (on the NMR time scale) Z E isomerization about the CÍN bond in the quinonimine fragment. N-(N-Arylsulfonylacetimidoyl)-1,4-benzoquinonimines in solution give rise to dynamic Z E-isomerization with respect to the CÍN bond in the N-arylsulfonylacetimidoyl fragment.     

Polyazanaphthylene nucleosides II. Synthesis of β-D-ribofuranosyl derivatives of 4-quinazolone

The preparation of N¹ (2,3-O-isopropylidene-β-D-ribofuranosyl)-4-quinazolone ( 6 ) and N³-β-D-ribofuranosyI-4-quinazolone ( 3b ) are reported. The N³ derivative was prepared by the direct condensation of 4-trimethylsilyloxyquinazoline ( 2 ) and 2,3,5-tri-O-benzoyl- D - ribofuranosyl bromide. The N¹ derivative was prepared from the previously reported N¹ -β-D-ribofuranosyl-2,4-quinazolinedione via the cyclonucleoside 4 .     

SYNTHESIS AND NMR SPECTROSCOPIC STUDY OF NEW 5-METHYLFURYL-CONTAINING SCHIFF BASES AND RELATED BIS(AMINOPHOSPHONATES)

The synthesis of three novel 5-methylfuryl-containing Schiff bases: N,N′-bis(5-methylfurfurylidene)-4,4′-diaminodiphenylmethane, N,N′-bis(5-methylfurfurylidene)-1,4-phenylenediamine, and N,N′-bis(5methylfurfurylidene)benzidine and the corresponding bis(aminophosphonates) derived from them, 4,4′-bis{N-methyl(diethoxyphosphonyl)-1-[(5-methyl)-2-furyl]} diaminodiphenylmethane, 1,4-bis { N-methyl(diethoxyphosphonyl)-1-[(5-methyl)-2-furyl]} diaminobenzene, and bis{N-methyl(diethoxyphosphonyl)-1-[(5-methyl)-2-furyl]}- benzidine, is reported. The compounds have been characterized by elemental analysis, TLC, IR, and NMR ( ¹ H, ¹³ C, and ³¹ P) spectra. For comparison, new ¹³ C and ³¹ P NMR data of three furyl-containing analogues of the above bis(aminophosphonates) are also regarded. The NMR studies of the two series of bis(aminophosphonates) reveal the presence of one diastereomer (meso or racemic form).     

Synthesis and Properties of a 2-Diazohistidine Derivative: A New Photoactivatable Aromatic Amino-Acid Analog

N^α[(tert-Butoxy)carbonyl]-2-diazo-L -histidine methyl ester 1 was synthesized starting from the corresponding L-histidine derivative. The physico-chemical properties of this new photoactivatable amino-acid derivative were established. The synthetic precursor of 1 , 2-amino-L -histidine derivative 3 , was best isolated and characterized as 2-amino-N^α-[(tert-butoxy)carbonyl]-N^τ-tosyl-L -histidine methyl ester ( 4 ). Selective deprotections of 4 (N^α-Boc, N^α-Tos, COOMe) were achieved, thus allowing the use of the corresponding products in peptide synthesis. The optically active dipeptides 8 and 9 were synthesized by coupling 2-amino-N^τ-tosyl-L -histidine methyl ester ( 5 ) with N-[(tert-butoxy)carbonyl]-L -alanine and N^α-[(tert-butoxy)carbonyl]-N^τ-tosyl-L -histidine ( 6 ) with L-alanine methyl ester, respectively. The question of selective diazotization of a 2-aminohistidine residue in a synthetic peptide was studied using competitive diazotizations between 2-amino-1H-imidazole and several amino-acid derivatives susceptible to undergo nitrosylation. The results show that synthetic photoactivatable peptides incorporating a 2-diazohistidine residue might become useful photoaffinity probes.     

Heterylation of 3-R1-5-R2-1,2,4-Triazoles with Derivatives of 3,5-Dinitro-1,2,4-Triazole

Heterylation of 3-R¹-5-R²-1'2'4-triazoles (pK _a 3-12) with N-alkyl-, N-alkenyl-, N-alkoxy-carbonyl-, N-oxoalkyl-, N-nitroxyalkyl, N-nitroaminoalkyl-3'5-dinitro-1'2'4-triazoles results insubstitution of a nitro group in 5 position of the dinitro compound yielding 1-R-methyl-3-nitro-5-(3-R¹-5-R²-1,2,4-triazolyl)-1,2,4-triazoles. The side processes: Hydroxide-ion attack on C⁵ and (or) N¹ of the ring both in the substrate and in the target compound afford 1-R-methyl3-nitro-1,2,4-triazol-5-ones, 3,5-dinitro-1,2,4-triazole and NH-acids of N-C-bitriazole series. Optimal reaction media are aprotic dipolar substances, and for compounds prone to heterolysis ethyl acetate-water systems. The azole pK _a is the decisive factor controlling the composition and the ratio of reaction products. The process is promising for azoles with pK _a > 5, and the optimal range of pK _a is 8-10.     

Synthesis of Dipeptides via Addition of N-(Nitroacetyl)amino-Acid Derivatives to Michael Acceptors: Scope,Stereoselectivity, and Absolute Configuration

Michael addition of N-nitroacetyl derivatives 1 of proline esters using KF under phase-transfer catalysis resulted in the formation of adducts 3–9 with chemical yields ranging from 40–90% (Scheme). Stereoselectivity of up to 51% was obtained on addition of benzyl N-(nitroacetyl)-L -prolinate ( 1a ). The absolute configuration at the newly created chiral centre was established in the case of 9 by carrying out a reductive acylation and comparing the product 10 with an authentic sample of ethyl N-(O⁵-ethyl N²-acetyl-L -glutam-1-yl)-L -prolinate (L, L - 10 ).     

13C nuclear magnetic resonance spectroscopy of selected adenine nucleosides: Structural correlation and conformation about the glycosidic bond

Structural correlations have been carried out from ¹³C chemical shifts (δ) and by analysis of ¹J(CH) coupling constants, and the conformation about the glycosidic bond has been studied by means of the ³J(CH) vicinal coupling constants between C-8 and H-1′ of some adenine nucleosides such as adenosine (Ado), N(7)-β-D-ribofuranosyladenine (N(7)-Ado), N(9)- and N(7)-β-D-xylofuranosyladenine (N(9)-xylAde and N(7)-xylAde), N(9)-(3-chloro-3-deoxy-β-D-xylofuranosyl)adenine (3′-Cl-xylAde) and N(9)-(2-chloro-2-deoxy-β-D-arabinofuranosyl)adenine (2′-Cl-araAde). The analysis of the influence on δ¹³C of the nature and configuration of the substituent in the carbohydrate fragment of the molecule has revealed two types of effects, namely, 1,2-cis and 1,2-trans. This approach, as well as the ³J(CH) values and the analysis of the C-3′-endo?C-2′-endo equilibrium of the carbohydrate fragment of nucleosides, and circular dichroism (CD) data, provides important information on the conformation about the glycosidic bond. The magnitudes of ³J(C-4, H) are indicative of the position of attachment of the carbohydrate fragment to the heterocyclic base.     

Inversion-Voltammetric Determination of Heavy Metal Ions on Electrodes Modified with Mono- and bis-N-Thiophosphoryl Thiourea

A method is proposed for determining Ni^{2 +}, Co^{2 +}, Cu^{2 +}, Cd^{2 +}, and Pb^{2 +} ions by inversion voltammetry on carbon-paste electrodes modified with N-diisopropoxythiophosphoryl-N'-phenyl thiourea and its derivatives: N,N'-bis-(diisopropoxythiophosphorylamidothiocarbonyl)-1,5-diamino-3-oxapentane, N,N'-bis- (diisopropoxythiophosphorylamidothiocarbonyl)-1,8-diamino-3,6-dioxaoctane and N,N'-bis-(diisopropoxythio- phosphorylaminothiocarbonyl)-1,10-diaza-18-crown-6.     

Electrospray-Ionization Mass Spectrometry. Part 2. Neighboring-Group Participation in the Mass-Spectral Decomposition of 4-Hydroxycinnamoyl-spermidines

The three mono substituted N-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines 1–3 have been studied by positive-ion electrospray-ionization tandem mass spectrometry (ESI-MS/MS). Because of the neighboring-group participation, the MS/MS of [ 1 + H]⁺ and [ 2 + H]⁺ are essentially similar, while compound 3 can be easily distinguished from 1 and 2 because of the characteristic ions at m/z 218. However, with the source collision-induced dissociation (source-CID) MS/MS technique, the compounds 1 and 2 can be unambiguously distinguished by the signal of the pyrrolidinium ion (m/z 72) from their daughter ion (m/z 275). The source-CID MS/MS of the labeled compound N-(4-aminobutyl)-N-(3-aminopropyl)-N-[3-(4- hydroxyphenyl)prop-2-en[¹⁵N]amide] ([¹⁵N(4)]- 2 ) provide more information on the decomposition mechanisms and proved the occurrence of a partial transamidation reaction 2→1 during the measurement.     

Investigations of Steric and Electronic Factors Influencing the Cyclopalladation of meta-Toluidine Analogues

The cyclopalladation of two different types of aniline derivatives is described: the acetylated anilines N-(3-methylphenyl)acetamide ( 2a ), 3-(acetylamino)-4-chlorobenzoic acid ( 2c ), and N-(2-chlorophenyl)acetamide ( 2d ) are cyclometalated easily with palladium(II) acetate and trifluoroacetic acid to yield the corresponding complexes 4a, 4c , and 4d , respectively, whereas the acetylated meta-toluidine N-(2-chloro-5-methylphenyl)acetamide ( 2b ) cannot be metalated at the only accessible site between the acetylamino and the methyl group. This aromatic C? H bond can be activated, however, with the second type of meta-toluidine derivatives: the 2-chloro-5, N-dimethyl-N-nitrosoaniline ( 3b ) readily undergoes cyclopalladation to yield the corresponding Pd^II complex di-μ-trifluoro-acetato-bis[3-chloro-6-methyl-2-(N-methyl-N- nitrosoamino)phenyl-C,N? O]dipalladium(II) ( 5b ) containing a five-membered palladacycle with coordination of Pd^II at the nitroso N-atom, which is established by ¹⁵N-NMR spectroscopy.