Synthesis and thermal transformations of pyrazolines obtained by 1,3-dipolar addition of diazocyclopropane to maleimides

1-Pyrazolines, obtained by 1,3-dipolar cycloaddition of diazocyclopropane to N-phenyl- and N-cyclohexylmaleimides, undergo complete dediazoniation at 175 °C for 10–16 h with the formation of spiro[3-azabicyclo[3.1.0]hexane-6,1′-cyclopropane]-2,4-diones 3 (80–89%) and isomeric 3-cyclopropyl-1H-pyrrole-2,5-diones 4. On the example of 3-cyclopropyl-1-phenyl-1H-pyrrole-2,5-dione, it was shown that compounds 4 are able again to enter into 1,3-dipolar cycloaddition with diazomethane or diazocyclopropane with the reaction in the case of diazocyclopropane being nonselective and leading to two regioisomeric pyrazolines in the ratio ∼1.7: 1, thermolysis of which, conversely, proceeds with high selectivity and exclusively affords a spiropentane derivative. An action of the aqueous methanol solution of sodium hydroxide on the spiropentanes fused with succinimide fragment and subsequent acidification of the salts obtained lead to stable cis-amidoacids of spiropentane series. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1680–1685, August, 2008.     

Addition of diazocyclopropane generatedin situ to vinyl bromide and chemical transformations of the resulting 5-bromospiro(1-pyrazoline-3,1′-cyclopropane)

The reaction of diazocyclopropane generatedin situ with vinyl bromide occurs as regioselective 1,3-dipolar cycloaddition to give 5-bromospiro(1-pyrazoline-3,1′-cyclopropane) in ∼60% yield. Reactions of the latter with nucleophilic reagents, which can occur both with retention and opening of the cyclopropane ring, were studied. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 688–690, April 1998.     

Five-membered 2,3-dioxo heterocycles: LXXVI. Reaction of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

Methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione to give methyl 11-aryl-12-benzoyl-9-hydroxy-4,6-dimethyl-3,5,10-trioxo-4,6,8,11-tetraazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates which underwent thermal recyclization to 1-aryl-3-benzoyl-4-hydroxy-1′,3′-dimethylspiro[pyrrole-2,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,5,6′(1H,1′H,3′H,7′H)-tetraones.     

Synthesis of 1,3,4-thiadiazolo[3′,2′∶1,2]pyrimidino[5,6-d]-1,3-thiazine derivatives

2-R-5-Imino-6H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-ones react with aromatic and heterocyclic aldehydes in the presence of Et₃N to give condensation products on the methylene group, which react with carbon disulfide to yield the corresponding 2,6-disubstituted 8-thioxo-9,9a-dihydro-1,3,4-thiadiazolo[3′,2′∶1,2]pyrimidino[5,6-d]1,3-thiazin-5-ones. Deceased. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 366–368, February, 1999.     

Reaction of methyl 1-bromocyclopentane- and 1-bromocyclohexanecarboxylates with zinc and 2-arylmethylidene-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2<Emphasis Type="Italic">H</Emphasis>)-ones

Methyl 1-bromocyclopentanecarboxylate and methyl 1-bromocyclohexanecarboxylate reacted with zinc and 2-arylmethylidene-2,3-dihydro-1H-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2H)-ones to give 4′-aryl-4′,5′-dihydro-2′H-spiro[cyclopentane(cyclohexane)-1,3′-indeno[1,2-b]pyran]-2′-ones or 4-aryl-5,6-dihydrospiro[benzo[h]chromene-3,1′-cyclopentane(cyclohexane)]-2(4H)-ones, respectively.     

4,4-dimethyl-4,5-dihydro-1,2-dithiolo-[3,4-c]quinoline-1-thiones in 1,3-dipolar cycloaddition reactions with acetylenic dipolarophiles

The behavior of 4,4-dimethyl-4,5-dihydro-1,2-dithiolo[3,4-c]quinoline-1-thiones in the 1,3-dipolar cycloaddition reaction with acetylenic dipolarophiles has been studied. The rate of cycloaddition is reduced along with the decrease of electron-deficiency of the triple bond. Substituted 4-(1′,3′-dithiol-2′-ylidene)-1,2-dihydroquinoline-3-thiones were shown to be the reaction products. On using a twofold excess of acetylenedicarboxylic acid dimethyl ester, adducts of composition 1∶2 were formed which occured to be substituted 1′, 3′-dithiole-2′-spiro-1-(5,6-dihydrothiino[2,3-c]quinolines). Voronezh State University, Voronezh 394693, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 656–660, May, 1999.     

Oxidation of camphor ethylene dithioacetal

(1R,1′R,2S,4R)-1,7,7-Trimethylspiro[bicyclo[2.2.1]heptane-2,2′-[1,3]dithiolane] 1′-oxide, (1R,2S,3′R,4R)-1,7,7-trimethylspiro[bicyclo[2.2.1]heptane-2,2′-[1,3]dithiolane] 1′,1′,3′-trioxide, and (1R,4R)-1,7,7-trimethylspiro[bicyclo[2.2.1]heptane-2,2′-[1,3]dithiolane] 1′,1′,3′,3′-tetraoxide were synthesized by oxidation of camphor ethylene dithioacetal with m-chloroperoxybenzoic acid at different substrate-tooxidant ratios. The structure of the products was proved by IR and NMR spectroscopy and X-ray analysis.     

Reaction of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with naphthalen-1-amine,quinolin-8-amine,and 1,3-diketones

Condensation of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with naphthalen-1-amine and cyclohexane-1,3-dione, methyl 2,2-dimethyl-4,6-dioxocyclohexane-1-carboxylate, or dimedone gave the corresponding 7-(2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-yl)-7,8,9,10,11,12-hexahydro-12H-benzo[c]acridin-8-ones. The reaction of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with naphthalen-1-amine and indan-1,3-dione produced 7-(2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-yl)-8H-benzo[h]indeno[1,2-b]quinolin-8-one. 7-(2′-Hydroxy-1,1′: 3′,1″-terphenyl-5′-yl)-7,8,9,10,11,12-hexahydrobenzo[b][1,10]phenanthrolin-8-ones were obtained by three-component condensation of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with quinolin-8-amine and cyclohexane-1,3-dione, methyl 2,2-dimethyl-4,6-dioxocyclohexane-1-carboxylate, or dimedone.     

Synthesis of new spiro compounds containing a carbamate group

1,3-Dipolar cycloaddition to methyl 4-[2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)-1-oxoethyl]-phenylcarbamate of diazomethane in chloroform-diethyl ether and of 3,4-dimethoxybenzonitrile oxide generated from the corresponding aldehyde oxime by the action of N-chlorobenzenesulfonamide sodium salt (Chloramine B) in boiling ethanol gave, respectively, methyl 4-(2-oxo-1′,5′-dihydro-1H-spiro[indole-3,4′-pyrazol]-3′-ylcarbonyl)phenylcarbamate and methyl 4-[3′-(3,4-dimethoxyphenyl)-2-oxo-1H,4′H-spiro[indole-3,5′-isoxazol]-4′-ylcarbonyl]phenylcarbamate. The condensation of methyl 4-[2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)-1-oxoethyl]phenylcarbamate with hydrazine hydrate in ethanol afforded methyl 4-(2-oxo-1,2,2′,4′-tetrahydrospiro[indole-3,3′-pyrazol]-5′-yl)phenylcarbamate.     

A Dehydrogenated Cycloadduct of N-Phenylmaleimide and the Azomethine Ylide Derived from Ninhydrine and Phenylalanine: Structure and Conformation

Summary.  The structure of the dehydrogenation product 1′,3a′-dihydro-3′-((1,3-dioxoindan-2-ylidene)-phenyl-methyl)-5′-phenyl-spiro-(indan-2,1′-pyrrolo[3,4-c]pyrrole)-1,3,4′,6′-(5′H, 6a′H)-tetrone derived from the cycloadducts (±)-(3a′S,6a′R)-1′,3a′-dihydro-3′-((R)-α-(1,3-dioxoindanyl)-benzyl)-5′-phenyl-spiro-(indan-2,1′-pyrrolo[3,4-c]pyrrole)-1,3,4′,6′(5H,6a′H)-tetrone and/or (±)-(3a′S,6a′R)-1′,3a′-dihydro-3′-((S)-α-(1,3-dioxoindanyl)-benzyl)-5′-phenyl-spiro-(indan-2,1′-pyrrolo[3,4-c]pyrrole)-1,3,4′,6′(5H,6a′H)-tetrone, which were synthesized by 1,3-dipolar cycloaddition of N-phenylmaleimide to 2-((2-(1,3-dioxoindan-2-yl)-2-phenyl-ethenyl)-imino)-indan-1,3-dione, was determined by X-ray analysis. Crystal data (CCD, 180 K): rhombohedral, R&3macr;;, a = 34.0871(7), c = 13.9358(5) ?, Z = 18; the structure was solved by direct methods and refined by full-matrix least-squares procedures to R(F, I ≥ 3σ(I)) = 0.053. The molecule contains a central folded ring system of two cis-fused 5-membered heterocyclic rings; each ring is nearly planar, and the angle between the rings amounts to 59.0°. Dynamic ¹H NMR spectroscopy of the product revealed an exchange process caused by restricted rotation of the double bonded 1,3-indandione moiety and the phenyl group about the C_sp2-C_sp2 single-bonds. Molecular modeling and complete lineshape analysis indicated a four site exchange process for which free energies of activation and free energies could be established. ΔG ^‡ values for the barriers of rotation are in the range of 57–59 kJ · mol^− 1 at 273 K, which is unusually high for an unsubstituted phenyl group. Received May 3, 2001. Accepted (revised) June 8, 2001     

Five-membered 2,3-dioxo heterocycles: LXX. Spiro heterocyclization of 1H-pyrrole-2,3-diones by the action of 1,5-binucleophiles. Crystalline and molecular structure of ethyl 1′-benzyl-7-methoxy-3,3-dimethyl-1,2′-dioxo-5′-phenyl-1′,2,2′,3,4,10-hexahydro-1H-spiro[acridine-9,3′-pyrrole]-4′-carboxylate

Ethyl 1-alkyl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates reacted with 3-arylamino-5,5-dimethylcyclohex-2-en-1-ones as carbon-centered 1,5-binucleophiles to give the corresponding substituted ethyl 1′-alkyl-3,3-dimethyl-1,2′-dioxo-5′-phenyl-1′,2,2′,3,4,10-hexahydro-1H-spiro[acridine-9,3′-pyrrole]-4′-carboxylates whose structure was proved by X-ray analysis.     

Comparative quantum chemical investigation of structures and properties of diazocyclopropane and other diazoalkanes

The electronic structures and dissociation energies of diazocyclopropane (1), diazomethane (2), 2-diazopropane (3), and diazocyclobutane (4) were calculated at the density functional B3LYP and the ab initio MP2 levels using the 6-31G(d) basis set and at the G2(MP2,SVP)//B3LYP/6-31G(d) level. Distinctive features of diazocyclopropane 1 are the low energy of dissociation with loss of the nitrogen molecule; ΔE = 18.7 kcal mol⁻¹, B3LYP; 9.2 kcal mol⁻¹, G2 at 0 K) and a nonplanar structure, in which the C=N bond forms an angle of 115.7° with the plane of the cyclopropane ring. The behavior of molecules 1 and 2 in the 1,3-dipolar cycloaddition to ethylene (5), acrylonitrile (6), and methyl acrylate (7) was studied. The reactions of 1 with 6 and 7 have very low activation barriers (ΔE _a = 4.7 and 4.4 kcal mol⁻¹, respectively; at the B3LYP level). For these reactions, the G2 method gives even smaller activation parameters (1.8 and 0.3 kcal mol⁻¹, respectively). The results of our calculations provide a good explanation for high reactivity of diazocyclopropane 1. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1072–1076, May, 2005.     

Synthesis of a Bifunctional 1,1′-Diphenyl-1,2,3,4-tetrahydroquinoline Derivative: 1,1′-Diphenyl-1,2,3,4,1′,2′,3′,4′-octahydro-6,6′-biquinolinyl-3,3′-diol

Summary. Intramolecular cyclization of N,N′-di(3-chloro-2-hydroxy)propyl-N,N′-diphenylbenzidine occurs to give bis-1,2,3,4-tetrahydroquinoline derivative 1,1′-diphenyl-1,2,3,4,1′,2′,3′,4′-octahydro-6,6′-biquinolinyl-3,3′-diol.     

New alkaloids from <Emphasis Type="Italic">Casimiroa edulis</Emphasis> fruits and their pharmacological activity

The extract of Casimiroa edulis was investigated for antihypertensive activity. The ethanol and total alkaloids (in chloroform) extracts were found to have antihypertensive properties at doses of 500 and 200 mg/kg, respectively. Four quinolinone alkaloids were isolated and identified as: 2-(2′-hydroxy-4′-methoxyphenyl)-5,8-dimethoxy-3-propyl-1H-quinolin-4-one (1), 5,8-dimethoxy-2-(3′-methoxyphenyl)-3-propyl-1H-quinolin-4-one (2), 5,8-dimethoxy-2-(3′,4′-dimethoxyphenyl)-3-propyl-1H-quinolin-4-one (3), and 5,6-dimethoxy-2-(2′,5′,6′-trimethoxyphenyl)-1H-quinolin-4-one (4). Interestingly, compounds 1, 2, and 3 were found to be new alkaloids. The four isolated alkaloids showed antihypertensive activity at doses of 50, 100, 200, and 300 mg/kg, respectively. Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 473–476, September–October, 2007.     

Studies on the Synthesis and Potentiometric Properties of Three Novel Tripodal Ligands and their Complexes

Three novel tripodal ligands, N,N′,N′′-tri-(3′-phenylpropionic acid-2′-yl-)-1,3,5-triaminomethylbenzene (Ll), N,N′,N′′-tri-(4′-methylvaleric acid-2′-y1-)-1,3,5-triaminomethylbenzene (L2) and N,N′,N′′-tri-(3′methylvaleric acid-2′-yl-)-1,3,5-triaminomethylbenzene (L3), have been synthesized and fully characterized. The stabilizing ability of complexes of the three ligands with transition metal ions Cu(II), Ni(II), Zn(II) and Co(II) and rare earth metal ions La(III), Nd(III), Sm(III), Eu(III) and Gd(III) has been investigated by the pontentiometric method in water and in aqueous KNO₃ (0.1 mol dm⁻³) at 25.0±0.1 °C, respectively. The results show that there is a great deal of difference between two series of complexes’ stabilities. An explanation of the difference has been given.     

An efficient method for the synthesis of 9-β-D-2′-deoxyribofuranosyl-6-methylpurine

A new method for the preparation of 9-β-D-2′-deoxyribofuranosyl-6-methylpurine from inosine (1) is described. Inosine was converted to 6-chloropurinenucleoside (4) via acetylation, chlorination, and deacetylation. Compound 4 was transformed to the key intermediate 6-methylpurinenucleoside (7) via protection of the 2′,3′,5′-hydroxy groups of 4 with 3,4-dihydropyran to give compound 5, then methylation at the 6-position of 5 with dimethyl copper lithium gave compound 6; depyranylation of 6 led to the subsequent selective protection of the 3′,5′-hydroxy groups of 7 with O[Si(I-Pr)₂Cl]₂ followed by reaction with phenyl chlorothionoformate to give compound 9. Compound 9 was then converted to the target compound 11 via 2′-deoxidation and 3′, 5′-desilylation. The structures of these products were identified by Mass Spectrum (MS), ¹H-NMR (Nuclear Magnetic Resonance) spectra and elemental analysis. Translated from Chinese Journal of Organic Chemistry, 2006, 26(10): 1394–1397 (in Chinese)     

Reactions of N , N -Disubstituted 5-Arylmethylidene-2-amino-thiazol-4(5 H )-ones with CH Acids

 N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with diethyl malonate, ethyl benzoylacetate, acetylacetone, or cyclopentadiene in refluxing toluene and in presence of powdered sodium to give the respective 5-arylmethylidene-2′-amino-2,5′-bithiazolylidene-4,4′-dione derivatives in moderate yields. 5-Benzylidene-2-morpholin-4-yl-2-thiazol-4(5H)-one reacted with malononitrile in toluene and in presence of powdered sodium under mild conditions to afford the 1:1 adduct, benzylmalononitrile, and 2-morpholin-4-yl-2-thiazol-4(5H)-one. However, similar treatment of 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-one with malononitrile yielded the 2,5′-bithiazolylidene-4,4′-dione derivative together with 4-methoxyphenylmethylidene malononitrile. Treatment of 5-benzylidene- and 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-ones with 3-phenyl-4-oxo-2-thioxo-1,3-thiazolidine in refluxing toluene and in presence of powdered sodium produced 5-arylmethylidene-3-phenyl-4-oxo-2-thioxo-1,3-thiazolidines in good yields. The structures of all products were deduced from microanalytical and spectroscopic data, mechanistic details are discussed.     

Synthesis and structure of 4′,4′-dimethyl[16α,17α]spiropentanopregn-4-ene-3,20-dione

4′,4′-Dimethyl[16α,17α]spiropentanopregn-4-ene-3,20-dione was synthesized. The addition of diazo-2,2-dimethylcyclopropane generated from N-(2,2-dimethylcyclopropyl)-N-nitrosourea to 16,17-didehydropregnenolone acetate occurs regio-and stereospecifically to give 3β-acetoxy-1′,1′-dimethyl-20-oxopregn-5-ene-[16α,17α;7′,6′]-4′, 5′-diazaspiro[2.4]-hept-4′-ene in high yield. Its thermolysis affords a spiropentane-containing steroid, which is transformed into the target diketone. The anti position of the gem-dimethyl group in the fused spiropentane fragment is evident from the X-ray diffraction study of the final product. Dedicated to Academician O. M. Nefedov on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2040–2042, November, 2006.     

Acylation of spiro(1-pyrazoline-3,1′-cyclopropanes) to form 1-acyl-3-(2-chloroethyl)-2-pyrazolines and transformation of bicyclic 2-pyrazolines into 1,4,5,6-tetrahydropyridazines

Strained polycyclic spiro(1-pyrazoline-3,1-cyclopropanes) react with acetyl or benzoyl chlorides at 0–15 °C regioselectively to give in high yields corresponding 1-acyl-3-(2-chloro-ethyl)-2-pyrazolines. Under the same conditions 6-ethenyl-4,5-diazaspiro[2,4]hept-4-ene gives a mixture of two pyrazolines resulting from the acyl group attack directed at different nitrogen atoms. Bicyclic pyrazolines-2 obtained by acylation of the cycloaddition products of diazocyclopropane with 3,3-disubstituted cyclopropenes transform under the action of hydrogen chloride to 1,4,5,6-tetrahydropyridazines in high yields.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2208–2211, November, 1995.The work was carried out with financial support of the Russian Foundation for Basic Research (Grant No. 94-03-08902).     

Reaction of N-Heterocycles with Acetylenedicarboxylates in the Presence of N-Alkylisatins or Ninhydrin. Efficient Synthesis of Spiro Compounds

Summary. The 1,3-dipolar intermediates generated by addition of isoquinoline, to dialkyl acetylenedicaboxylates are trapped by N-alkylisatins to produce dialkyl 1,2-dihydro-2-oxo-1-alkylspiro[3H-indol-3,2′-[2H,11bH][1,3]oxazino[2,3-a]isoquinoline]-3′,4′-dicarboxylates in excellent yields. The reaction of isoquinoline, quinoline, or pyridine with dimethyl acetylenedicarboxylate in the presence of ninhydrin led to dimethyl 1,2-dihydro-1,3-dioxospiro[3H-indene-3,2′-[2H,11bH][1,3]oxazino[2,3-a]isoquinoline]-3′,4′-dicarboxylate, dimethyl 1,2-dihydro-1,3-dioxospiro[3H-indene-3,3′[3H,4aH][1,3]oxazino[3,2-a]quinoline]-1,2-dicarboxylate, or dimethyl 1,2-dihydro-1,3-dioxospiro[3H-indene-3,2′-[2H,9aH]pyrido[2,1-b][1,3]oxazino]-3,4-dicarboxylate.