Research on benzodiazines

2-Methyl-4-hydrazinoquinazoline is shown to give on diazotization a covalent hydration product, 5, 5-dihydro-5-methyl-5-hydroxytetrazolo [1, 5-c]quinazoline (V). 2-phenyl-4-hydrazino-quinazoline gives the nonhydrated 5-phenyltetrazolo [1, 5-c]-quinazoline (IIb). Hydrolysis of the hydrated 5-methyl derivative V is shown to result in opening of the pyrimidine ring and formation of 5-(2-aminophenyl)tetrazole, while hydrolysis of the 5-phenyl derivative IIb is found to give, via the azide, 2-phenylquinazoline. Possible reasons for the different behavior on hydrolysis are considered.For Part VII see [1].     

Substituted pyridines. preparation of substituted stilbazoles and their reactions

5-Phenyl-9-bromotetrazolo[1, 5c]quinazoline (I) was synthesized. It was shown that I is covalently hydrated at the N₍₆₎=C₍₅₎ bond. The structure of the covalent hydrate (V) was confirmed by cleavage to 5-(2-amino-5-bromophenyl) tetrazole. The probable mechanisms of the covalent hydration and cleavage are examined. V was converted to the 5-methyl derivative (VII).For part X, see [1].     

Acetals of lactams and acid amides. 35. Synthesis of condensed two- and three-ring pyridine systems on the basis of enamino amides

The synthesis of 2,3,5,6-tetrahydropyrrolo[3,2-c]pyrid-6-one was accomplished by rearrangement of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1, 2-c]pyrimidine. Pyrrolo[3,2-c]pyrimidine, 1,6-naphthyridine, and pyrimido[4,3-b]-azepine derivatives were synthesized on the basis of enamino dinitriles. The hydrolysis of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1,2-c]-pyrimidine in 50% CH₃COOH leads to a pyrrolo[1,2-c]pyrido[4,3-d]pyrimidine derivative. A similar dipyrido[4,3-d-1,2-c]pyrimidine derivative was obtained from 1-cyano-9-dimethylaminomethylene-2,5,6,7,8,9-hexahydropyrido[1,2-c]pyrimidine under these conditions, and 3,4-dioxo-3,4,7,8,9,10-hexahydropyrido[1,2-c]pyrano[4,3-d]-pyrimidine was synthesized bytreatment with a 1 N solution of HCl.See [1] for Communication 34.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 518–522, April, 1982.     

Azide-tetrazole tautomerism of diazidodiazines and their benzo analogs

It has been discovered with the aid of IR and NMR spectroscopy that 5-azidotetrazolo [1,5-a]quinazoline exists in solutions in a tautomeric equilibrium with ditetrazolo [1,5-a:1,5-c]quinazoline, and the thermodynamic and kinetic characteristics of the equilibrium have been determined. Azide-tetrazole tautomerism is not observed under these conditions for ditetrazolo[1,5-a:5,1-c]pyrazine, 6-azidotetrazolo [1,5-b]pyridazine, and their benzo analogs.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2002–2007, September, 1989.     

Studies in the imidazole series

Methods were developed for the synthesis of dihydro and tetrahydro derivatives of imidazo-[1,2-a]- and imidazo[1,2-c]pyrimidine and imidazo[2,1-b]-5-quinazolone from 2-amino- and 4-aminopyrimidines, 2-amino-4-quinazolones, and -haloethanols or 1,2-dihaloethanes. Dihydroimidazo[1,2-c]quinazoline, which was also obtained by cyclization of 4-(-hydroxyethylamino)-quinazoline, was synthesized by reaction of 4-chloroquinazoline with -haloethylamines.See [1] for communication LXXXV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 834–836, June, 1976.     

Studies on the Cyclisation of 4-[2′-Cyclohexenyl]-3-hydroxy[1]benzopyran-2-one

The bicyclic coumarin derivative-1, 3 propano-2-bromo-1,2-dihydro-3H-pyrano [2, 3-c] [1]benzo-pyran-5-one (8) was synthesised by a sequence of reaction viz. acetylation of 4-[2′-cyclohexenyl] -3-hydroxy [1] benzopyran-2-one (4), addition of bromine to cyclohexenyl double bond and treating the resulting acetyldi-bromo derivative (7) with 4% alcoholic KOH. Benzofuro [2, 3-c] [1] -benzopyran-6-one (10) was synthesised from 4 via oxymercuration with mercuric acetate in methanol followed by dehydrogenative damercuration with Pd-C in refluxing diphenyl ether.     

Cyclization of N-(4-quinazolyl)-α-amino carboxylic acids

2,3-Dihydroimidazo[1,2-c]quinazolin-2-one derivatives were obtained by cyclization of N-(4-quinazolyl)--amino carboxylic acids. A scheme including cleavage of the C(₂)-N(₃) bond of the quinazoline ring and subsequent rearrangement is proposed for the mechanism of the cyclization. The structures of the synthesized compounds were established by means of chemical and physicochemical methods.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1268–1271, September, 1976.     

Some Transformations of 2-(Chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[<Emphasis Type="Italic">h</Emphasis>]quinazolin-4(3<Emphasis Type="Italic">H</Emphasis>)-one

The condensation of 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carbonitrile with chloroacetyl chloride afforded chloro-N-(2-cyano-3,3-dimethyl-3,4-dihydronaphthalen-1-yl)acetamide which underwent cyclization to 2-(chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one. The latter reacted with various nucleophiles (alkali metal alkoxides, piperazine, 2-sulfanylethanol) to give 2-(alkoxymethyl)-, 2-(piperazin-1-ylmethyl)-, and 2-{[(2-hydroxyethyl)sulfanyl]methyl}-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin- 4(3H)-ones. The condensation of 2-(chloromethyl)benzo[h]quinazoline with 2-thioxo derivatives of quinazoline and benzo[h]quinazolines led to the formation of bis-quinazolines in which 5,5-dimethyl-5,6- dihydrobenzo[h]quinazolin-4(3H)-one fragment is linked to quinazoline or benzo[h]quinazoline system through a CH₂S bridge.     

Derivatives of the androstane series

Conclusions 1. The synthesis of 17-hydroxyandrostano[3,2-c]pyrazole and of cholestano[3,2-c]pyrazole has been effected by the reaction of the corresponding 2-hydroxymethylene-3-oxosteroids with hydrazine hydrate.2. The mechanism of the formation of these pyrazoles has been studied. It has been shown that the reaction takes place in two stages, regardless of the substituent at C₁₇ of the steroid molecule, with the formation of the 2-hydroxymethylene-3-hydrazone and its dehydration to form the pyrazole derivative.Khimiya Prirodnykh Soedinenii, Vol. 6, No. 1, pp. 31–33, 1970     

Cyclisation of 4-[2-Cyclofentenyl]-3-Hydroxy [1] Benzopypan-2-One

4-[2-cyclopentenyl]-3-hydroxy [1] bonzopyran-2-one(3) was cyclised to the bicyclie coumar in-1,3-ethano-2-bromo-1,2-dihydro-3H-pyrano [2,3-c] [1] benzopyran-5-one (6) by a sequence of reactions viz. acetylation of 3, addition of bromine to cyclopenteny double bond and treating the resulting acetyldibromo compound (5) with 4% alcoholic KOH, Cyclisation of compound (3) with mercuric acetate in methanol gave condensed furan derivative 7 which on reductive demercuration with zinc borohydride in dimethoxyethane gave the 1,3-propano-1,2-dihydrofuro [2,3-c] [1] benzopyran-4-one, 8. Cyclisation of compound 2 with come. H₂SO₄ furnished a mixture of bicyclic derivative 9 ad furo coumarin derivative 8.     

Copper(II) Complexes with Ethyl [(Pyrazolo-1-carbothioyl)-amino]acetate Derivatives: Synthesis and Structure

Optically active derivative of the natural monoterpene (+)-3-carene, namely, ethyl (3bS,4aR)-[(3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazole-1-carbothioyl)-amino]acetate (HL¹) and ethyl [(3,5-dimethyl-pyrazole-1-carbothioyl)-amino]acetate (HL²) were synthesized. Paramagnetic complexes [CuL¹Cl] _n (I) and [Cu₂L² ₂Cl₂] (II) were prepared. According to X-ray diffraction data, complex Iwith anion of (+)-3-carene derivative has chain structure, whereas complex IIwith anion of HL², which has no carbocyclic fragments, is a pseudodimer. Organic anions act as tetradentate bridging, cyclic ligands forming five-membered CuN₃C and CuNOC₂metal cycles. Coordination polyhedron of Cu(ClN₂O + S) in complexes Iand IIis a square pyramid. The values of _efffor complexes Iand II(1.88 and 1.84 _B, respectively) are constant in the temperature interval 78–300 K, which means that the unpaired electrons of Cu(II) ions do not exhibit any noticeable exchange interactions.     

Researches on benzodiazines

2-R-Quinazolones have been synthesized (R=Me, Ph,-pyridyl,-furyl), and subsequently the 4-chlorides and the corresponding 2-R-4-hydrazinoquinazolines were obtained. By the reaction of orthoformic ester and nitric acid on the hydrazines, 5-R- [3, 4-c]-s-triazoloquinazolines and 5-R- [1, 5-c] tetrazoloquinazolines were prepared, respectively. The compounds in which R=Me differ considerably from compounds with other groups, both in color and stability of intermediate reaction products. 5-R- [1, 5-c] tetrazoloquinazolines are hydrolyzed by HCl into quinazol-4-ones.For Part IV see [1].     

Cyclization of pyrazolones: novel synthesis of pyrano,pyrido, pyrimido and spiropyrazole derivatives

Depending on the reaction conditions, two alternative cyclizations are possible for [3?+?3] cyclocondensation of pyrazolone derivative 1a and ethyl cyanoacetate of type pyrano [2,3-c] pyrazol-6(1H)-one 2 and pyrano [2,3-c] pyrazol-4(1H)-one 3. Keeping of enaminic system 3 and benzylidene malononitrile in the presence of catalytic amount of trimethylamine resulted in pyridine cyclization affording pyrazolopyranopyridine derivative 4, not 5. The pyrazolone derivative 6a was obtained as a result of the acid-mediated addition reaction between compound 1a, urea and/or ammonium thiocyanate. In addition, the bispyrazolone of type 6b was obtained from the condensation reaction of urea and pyrazolone derivative. The spiro compound 7 was obtained from the double-addition reaction of pyrazolone to cinnamoyl isothiocyanate. A one-pot three-component condensation of a 3-hydroxybenzaldehyde, pyrazolone 1a, urea and/or thiourea under Biginelli conditions resulted in tetrahydropyrazolo pyrimidine derivatives 8a and 8b, respectively. The acid-mediated reaction of benzaldehyde and pyrazolone derivative 1a in the presence of Ac₂O yielded styrylpyrazole derivative 9. The polyfunctionalized product 9 reacted with hydrazine to furnish pyrazolotriazoloe of type 10. Treatment of styrylpyrazole derivative 9 with aniline furnished the aniline derivative 11 and none of the expected polyheterocyclic derivative 12 was obtained. Compound 9 undergoes pyridine cyclization to produce 13 under the effect of urea. N-phenyl pyrazolone converted into pyrano-dipyrazolone derivative 14. Pyran of type 14 underwent a ring transformation upon treatment with urea and/or thiourea to give the same dipyrazolo pyrimidine derivative 15. The newly synthesized compounds were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, ESI/LC-MS and elemental analysis.     

Cobalt(II), nickel(II) and zinc(II) coordination compounds derived from aromatic amines

The structural and spectroscopic characterization of coordination compounds of four aromatic amines derived from benzimidazole, 2-aminobenzimidazole (L1), 1-(S-methylcarbodithioate)-2-aminobenzimidazole (L2), 2-(2-aminophenyl)-1H-benzimidazole (L3) and 6,6-dimethyl-5H-benzimidazolyl[1,2-c]quinazoline (L4) are reported. Cobalt(II) [Co(L1)₂(CH₃COO)₂] (1) and nickel(II) [Ni(L1)₂(CH₃COO)₂] (2) acetate coordination compounds of L1 are discussed. The synthesis and the X-ray crystal structure of the new 1-(S-methylcarbodithioate)-2-aminobenzimidazole (L2) is informed, together with its cobalt(II) [Co(L2)₂Cl₂] (3), [Co(L2)₂Br₂] (4) and zinc(II) [Co(L2)₂Cl₂] (5), [Zn(L2)₂Br₂] (6) coordination compounds. In these compounds the imidazolic nitrogen is coordinated to the metal center, while the ArNH₂ and the S-methylcarbodithioate groups do not participate as coordination sites. A co-crystal of L1 and L2 is analyzed. Structural analyses of the coordination compounds of L3 showed that this ligand behaves as a bidentate ligand through the aniline and the imidazole groups forming six membered rings in the cobalt(II) [Co(L3)Cl₂] (7) and zinc(II) [Zn(L3)Cl₂] (8) compounds, as well as the nickel(II) nitrate [Ni(L3)₂(H₂O)₂](NO₃)₂ (9). The quinazoline L4 was produced by insertion of one acetone molecule and water elimination in L3, its X-ray crystal diffraction analysis, as well as that of its zinc(II) coordination compound [Zn(L4)₂Cl₂] (10), are discussed.     

Synthesis and structure of 2-methyl-6-oxo-7,8-dihydrospiro(benzo[h]-triazolo[3,4-b]quinazoline-7,1′-cyclopentane)

The reaction of 4-amino-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1-cyclopentane) with benzoyl isothiocyanate led to the corresponding 4-(N-benzoylthioureido) derivative, the cyclization of which gave 4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]qquinazoline-5,1-cyclopentane). Condensation of the latter with hydrazine hydrate gave 2-hydrazino-3,4,5,6-tetrahydrospiro(benzo[h] quinazoline-5,1-cyclopentane), which formed 6-oxo-1H-7,8-dihydrospiro(benzo[h] triazolo[3,4-b] quinazoline7,1-cyclopentane) in reaction with orthoformice ester. Methylation of the product with methyl iodide led to its 2-methyl derivative.Communication 1, see ref. [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 658–662, May, 2000.     

Pyrimidines

3-Arylbenzo[f]quinazolines were obtained by reaction in acetic or propionic acid of -naphthylamine, ammonia, and aromatic aldehydes containing an NR₂ or OH group. A mechanism is proposed for the formation of monoarylbenzo[f]quinazolines from the corresponding intermediate 1,3-diaryldihydrobenzo [f] quinazolines by acid cleavage of the C-aryl bond in the 1 position. This mechanism was confirmed experimentally by establishment of the fact of cleavage of 1,3-bis (p-methoxyphenyl)-1,2-dihydrobenzo[f] quinazoline when the acidity of the medium is increased; 3-(p-methoxyphenyl) benzo [f] quinazoline and anisole were obtained in the reaction products. Condensation in the presence of formic acid gave -arylidene-N-formyl--naphthylamines rather than arylbenzo [f] quinazolines.See [1] for communication LXIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1265–1271, September, 1978.     

低价钛促进的苯并咪唑并[1,2-c]喹唑啉衍生物的合成

利用低价钛试剂促进的2-邻硝基苯基苯并咪唑与原甲酸酯或丙酮或固体光气的反应, 合成了一系列苯并咪唑并[1,2-c]喹唑啉衍生物, 化合物的结构经IR, 1H NMR, MS和元素分析确定, 化合物4c的结构经单晶X射线衍射分析进一步确证. 该方法具有原料易得、操作简便和产率高等优点.     

Synthesis and conformational analysis of new naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives

A new highly functionalized aminonaphthol derivative, 1-(amino(2-aminophenyl)methyl)-2-naphthol (4), was synthesized by the reaction of 2-naphthol, 2-nitrobenzaldehyde and tert-butyl carbamate or benzyl carbamate, followed by reduction and/or removal of the protecting group. The aminonaphthol derivative thus obtained was converted in ring-closure reactions with formaldehyde, benzaldehyde and/or phosgene to the corresponding naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives. The conformational analysis of some derivatives by NMR spectroscopy and accompanying molecular modelling are also reported.     

Synthesis of some new pyrazoloquinazolinone and quinazolinone derivatives

The benzoxazinone derivative 2‐(6,8‐dibromo‐4‐oxo‐4H‐benzo[d]‐1,3‐oxazin‐2‐yl)‐3‐(4‐methoxyphenyl) acrylonitrile ( 1 ) has been used as a starting material for preparation of the hitherto unknown pyrazoloquinazolinone and quinazolinone derivatives. Under different conditions the benzoxazinone ( 1 ) was reacted with hydrazine hydrate to provide the pyrazolocarbonitrile derivative ( 2 ) and the azine derivative ( 3 ) and/or the pyrazoloquinazoline derivative ( 4 ). When ( 4 ) was conducted to react either with EAA (ethyl acetoacetate) or Ac₂O/AcOH (acetic anhydride/acetic acid) mixture or phthalic anhydride/acetic acid mixture, the pyrazoloquinazoline carbonitrile ( 5 ), pyrazolo‐quinazoline acetic acid ( 6 ) or the pyrazoloquinazolinone derivative ( 7 ) were formed respectively. When ( 1 ) was reacted with phenylhydrazine, a mixture of the quinazolinone derivative ( 8 ) and the hydrazone derivative ( 9 ) were obtained. The benzoxazinone derivative ( 1 ) was found also to react with benzylamine in ethanol or without solvent to give the quinazolinone derivative ( 10 ) or the quinazolindione ( 11 ) respectively. Fusion of ( 1 ) with ammonium acetate yielded the quinazolinone ( 12 ), which was methylated to give ( 13 ) and thiated to the thioxyquinazoline derivative ( 14 ), while reaction of ( 1 ) with formamide gave the N‐formylquinazoline derivative ( 15 ).     

Condensed O-, N-heterocycles by the transformation of azidoacrylates

Summary A number of furo[3,2-c]pyridines (4a–4d) and benzo[b]derivative (4e), as well as pyrrolo[2,3-4,5]furo[3,2-c]pyridine (8) were prepared by reaction of the corresponding iminophosphoranes, available from ethyl azidoheteroacrylates and triphenylphosphine, with phenyl isocyanate. The appropriate azidoheteroacrylates were used for the preparation of some substituted furo[3,2-b:4,5-b]dipyrroles (6). The reactions of the prepared compounds are described.

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Kondensierte O-, N-Heterocyclen durch Umwandlung von Azidoacrylaten

Zusammenfassung Eine Anzahl von Furo[3,2-c]pyridinen (4a –4d), ein Benzo[b]derivat (4e) und Pyrrolo[2,3:4,5]furo[3,2-c]pyridin (8) wurden durch die Reaktion von Phenylisocyanaten mit den entsprechenden Iminophosphoranen dargestellt, die aus Ethyl-azidoheteroacrylaten und Triphenylphosphin leicht zugänglich sind. Die entsprechenden Azidoacrylate wurden zur Synthese einiger Furo[3,2-b:4,5-b]dipyrrole (6) verwendet. Die Reaktionen einiger dieser Verbindungen werden beschrieben.