Compounds IIIb Research Articles

Synthesis of new heterocyclic enamines and their cyclization with oxalyl chloride

Substituted furan-2,3-diones are convenient synthons exhibiting high reactivity and unusual chemical behavior toward various reagents [1, 2]. Heterocyclic ensembles derived from these compounds were found to possess versatile biological activity [3]. Functionally substituted furan-2,3-diones can be synthesized by reaction of heterocyclic β-enaminoketones with oxalyl chloride [4–6]. By reaction of diaroylacetylenes Ia and Ib with biphenyl-3,3′,4,4′-tetraamine (II) according to the procedure described in [7] we obtained new heterocyclic enamines, 2,2′-(3,3′-diaryl-1,1′,2,2′-tetrahydro-6,6′-biquinoxaline-2,2′-diylidene)bis(1-arylethanones) IIIa and IIIb (Scheme 1). Heating of compounds IIIa and IIIb with oxalyl chloride in boiling anhydrous chloroform led to the formation of new representatives of the furan-2,3-dione series, 4,4′-(3,3′-diaryl-6,6′-biquinoxaline-2,2′-diyl)bis(5-aryl-2,3-dihydrofuran-2,3-diones) IVa and IVb (Scheme 2). Presumably, bis-furandiones IVa and IVb are formed via initial acylation of compounds IIIa and IIIb with oxalyl chloride at the exocyclic =CH fragments to give intermediate acyl chlorides [8] which are converted into hydroxyenimine structure with subsequent intramolecular cyclization. 2,2′-(3,3′-Diphenyl-1,1′,2,2′-tetrahydro-6,6′-biquinoxaline-2,2′-diylidene)bis(1-phenylethanone) (IIIa). A solution of 4.68 g (20 mmol) of compound Ia in 10 ml of acetonitrile was added to a solution of 2.14 g (10 mmol) of tetraamine II in 20 ml of acetonitrile, and the mixture was heated to the boiling point and cooled. The precipitate was filtered off and recrystallized from acetonitrile. Yield 5.75 g (89%), orange– red crystals, mp 252–254°C (from acetone). IR spectrum, ν, cm: 3034 br (NH), 1580 br (C=O). H NMR spectrum, δ, ppm: 6.29 s (2H, CH), 6.93–7.90 m (26H, Harom), 15.70 s (2H, NH). Found, %: C 81.74; H 4.60; N 8.67. C44H30N4O2. Calculated, %: C 81.71; H 4.68; N 8.66. 2,2′-[3,3′-Bis(4-methylphenyl)-1,1′,2,2′-tetrahydro-6,6′-biquinoxaline-2,2′-diylidene]bis[1-(4-methylphenyl)ethanone] (IIIb) was synthesized in a similar way. Yield 5.98 g (85%), orange–red crystals, mp 223–225°C (from acetone). IR spectrum, ν, cm: 3024 br (NH), 1586 br (C=O). H NMR spectrum, δ, ppm: 2.34 s (6H, Me), 2.50 s (6H, Me), 6.35 s (2H, CH), 6.90–7.92 m (22H, Harom), 15.76 s (2H, NH). Found, %: C 82.09; H 5.43; N 7.95. C48H38N4O2. Calculated, %: C 82.03; H 5.45; N 7.97. 4,4′-(3,3′-Diphenyl-6,6′-biquinoxaline-2,2′-diyl)bis(5-phenyl-2,3-dihydrofuran-2,3-dione) (IVa). Oxalyl chloride, 2.52 g (20 mmol), was added to a solution of 6.47 g (10 mmol) of compound IIIa in 40 ml of anhydrous chloroform. The mixture was heated for

Synthesis of a New Series of 2-(2-Hydroxynaphthylazo)aryltellurium Compounds

A new series of 2-(2-hydroxynaphthylazo)arylmercury chlorides (Ia–Ib) were prepared by azo coupling of diazonium salts of 2-aminophenyl-, 2-amino-5-bromophenyl-, 2-amino-5-methylphenyl-, and 2-amino-5-nitrophenylmercury chlorides with 2-naphthol. Reactions of compounds Ia–Ib with tellurium tetrabromide in 1:1 and 2:1 molar ratios in dry dioxane gave 2-(2-hydroxynaphthylazo)aryltellurium tribromides (IIa–IId) and bis(2-(2-hydroxynaphthylazo)aryl)tellurium dibromides (IIIa–IIId), respectively, in good yields. Reduction of compounds IIa–IIc and IIIc–IIId by ethanolic hydrazine hydrate gave the corresponding ditellurides (IVa–IVc) and tellurides (Vc–Vd), respectively, in moderate to good yields. Treatment of compounds IIIb and IIId with [Pd(PPh3)4] in acetonitrile gave new symmetrical biaryls containing azo groups. All compounds were characterized by spectroscopic data and elemental analysis. GRAPHICAL ABSTRACT

Synthesis of a new organic anion by reaction of 4-aryl(hetaryl)-4-oxobutane-1,1,2,2-tetracarbonitriles with ammonia

4-Oxoalkane-1,1,2,2-tetracarbonitriles are known to react with concentrated aqueous ammonia to produce compounds of two types. Adducts of tetracyanoethylene and cyclic ketones (such as cyclopentanone and cyclohexanone) give rise to 2,7-diazabicyclic compounds [1], whereas from aliphatic tetracyanoethylated ketones isonicotinic acid derivatives are formed [2]. There are no published data on reactions of aqueous ammonia with tetracyanoalkanones derived from methyl aryl(hetaryl) ketones. When such reactions were carried out under the conditions reported in [1, 2], strong tarring occurred, and no individual products were isolated. By varying the conditions of this reaction we succeeded in obtaining ammonium 4-aryl1,1,2,2-tetracyano-4-oxobutan-1-ides IIa–IIc by mixing ketones Ia–Ic with a freshly prepared solution of ammonia in ethyl acetate at reduced temperature. Structures analogous to IIa–IIc but having singly charged metal cations were reported in [3, 4]. Compounds IIa–IIc turned out to be unstable in the solid state: on exposure to air they lost hydrogen cyanide with formation of ammonium 4-aryl-1,1,2-tricyano-4oxobut-2-en-1-ides IIIa–IIIc that are derivatives of a new organic anion. Intermediate formation of ammonium salts IIa–IIc is confirmed by their transformation into initial ketones Ia–Ic by the action of dilute hydrochloric acid immediately after isolation. Some structural similarity of salts IIIa–IIIc to betaines described in [5] may be noted. The latter were synthesized from tetracyanoethylene and pyridinium ylides. The structure of compounds IIIa–IIIc was confirmed by their IR, H NMR, and mass spectra and elemental analyses. The synthesis of salts III is an example of new reaction pathway of 4-oxoalkane1,1,2,2-tetracarbonitriles with ammonia. Ammonium 1,1,2-tricyano-4-(4-methoxyphenyl)4-oxobut-2-en-1-ide (IIIa). 4-(4-Methoxyphenyl)-4oxobutane-1,1,2,2-tetracarbonitrile (Ia), 0.139 g (0.5 mmol), was added to 2 ml of a freshly prepared solution of ammonia in ethyl acetate, cooled to –10°C, and the mixture was vigorously stirred until it became homogeneous. After several minutes, a solid separated and was filtered off, washed with cold ethyl acetate, and kept for 5–7 days on exposure to air. Yield 0.115 g (86%), mp 84–85°C. IR spectrum, ν, cm: 2230, 2199 (C≡N); 1667 (C=O). H NMR spectrum, δ, ppm: 3.81 s (3H, OCH3), 6.51 s (1H, CH), 7.01 d (2H, Harom), 7.07 br.s (4H, NH4), 7.79 d (2H, Harom). Mass spectrum: m/z 251 (Irel 49%) [M – NH3]. Found, %: C 62.51; H 4.77; N 20.95. C14H12N4O2. Calculated, %: C 62.68; H 4.51; N 20.88. Compounds IIIb and IIIc were synthesized in a similar way. Ammonium 1,1,2-tricyano-4-oxo-4-(2-thienyl)but-2-en-1-ide (IIIb). Yield 0.096 g (79%), mp 85– 87°C. IR spectrum, ν, cm: 2221, 2196 (C≡N); 1672 (C=O). H NMR spectrum, δ, ppm: 6.41 s (1H, CH), 7.16 d.d (1H, Harom), 7.19 br.s (4H, NH4), 7.65 d.d (1H, R = 4-MeOC6H4 (a), 2-thienyl (b), 3,4-(MeO)2C6H3 (c). ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 597–598. © Pleiades Publishing, Ltd., 2010. Original Russian Text © M.Yu. Belikov, O.V. Ershov, A.V. Eremkin, Ya.S. Kayukov, O.E. Nasakin, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 4, pp. 604–605.

4 + 2]-cycloaddition of alkyl vinyl ethers to 3-aroylpyrrolo[1,2-a]quinoxaline-1,2-dione

Reactions of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2diones with activated alkenes were not studied previously. We examined reactions of 3-(4-chlorobenzoyl)4-(4-chlorophenyl)pyrrolo[1,2-a]quinoxaline-1,2-dione (I) with alkyl vinyl ethers IIa and IIb at a ratio of 1 : 5 in boiling toluene (20–30 min, until violet color typical of initial compound I disappeared) and obtained new difficultly accessible bridged heterocyclic compounds, 16-alkoxy-2,14-bis(4-chlorophenyl)-15-oxa-3,10-diazatetracyclo[8.7.0.0.0]heptadeca-2,4,6,8,13pentaene-11,12-diones IIIa and IIIb. Compounds IIIa and IIIb are likely to be formed via thermal [4 + 2]cycloaddition of the O=C–C=C conjugated bond system in pyrrolo[1,2-a]quinoxaline-1,2-dione I at the polarized double C=C bond in vinyl ether IIa or IIb. crystallized from toluene. Yield 78%, mp 224–225°C. IR spectrum, ν, cm: 1728 (C=O), 1713 (C=O). H NMR spectrum, δ, ppm: 0.81 t (3H, CH3, J = 7.0 Hz), 2.18 d.d (1H, 17-H, J = 13.4, 4.6 Hz), 2.36 d (1H, 17-H, J = 13.4 Hz), 3.37 m (1H, OCH2), 3.44 m (1H, OCH2), 5.62 d (1H, 16-H, J = 4.6 Hz), 7.40– 7.93 m (12H, Harom). Found, %: C 65.75; H 4.38; N 5.15. C30H24Cl2N2O4. Calculated, %: C 65.82; H 4.42; N 5.12.

Reaction of salicylalkylenediimines with 2-chloro-4,5-diphenyl-1,3,2-dioxaphospholene

The structure of compounds IIIa–IIIc was proved by the IR, Н, and Р NMR spectroscopy, mass spectrometry, and composition, by the elemental analysis data. The IR spectra of the products IIIa–IIIc contain absorption bands at 1623–1627 (С=N) and 2590–2724 cm (broadened complex band, NH2). The chemical shift of the phosphorus atom at δP from –114 to –122 ppm is characteristic of the hexacoordinated phosphorus derivatives. Notice that the P NMR spectra of the reaction mixtures of IIIa–IIIc contain signals indicative of the formation of diastereoisomers mixture. As a result of fractional crystallization compound IIIa was obtained as the two diastereoisomers mixture in the ratio 1:1. Compounds IIIb and IIIc were isolated as individual diastereomers. Due to their salt structure the Н NMR spectra of compounds IIIa– IIIc contain poorly resolved signals, therefore only group analysis of the proton signals was performed on the basis of chemical shifts without considering the fine structure of the spectra. The transannular N→P bond (2.006–2.007 A) is realized in the compounds IIIa–IIIc. The intermolecular bonding of similar type was earlier observed in the series of pentacoordinated phosphorus derivatives [1–5]. On treating with triethylamine, the product IIIa undergoes dehydrochlorination to give phosphorate IVa of neutral structure (δР –105.87 ppm).

4+2]-cycloaddition of alkyl vinyl ethers to 4,5-diaroyl-1H-pyrrole-2,3-diones

Reactions of 4,5-diaroyl-1H-pyrrole-2,3-diones with activated alkenes were not reported previously. We examined the reaction of 1-aryl-4,5-diaroyl-1Hpyrrole-2,3-diones Ia and Ib with alkyl vinyl ethers IIa and IIb at a ratio of 1 : 1.5 in anhydrous benzene. The reaction mixtures were heated at 60–70°C until the bright red color typical of initial pyrrolediones I disappeared (25–30 min), and the products were 6-alkoxy-7a-aroyl-1,4-diaryl-7,7a-dihydropyrano[4,3-b]pyrrole-2,3(1H,6H)-diones IIIa and IIIb. Compounds IIIa and IIIb are likely to be formed via thermal [4 + 2]-cycloaddition of the conjugated O=C– C=C bond system in pyrrolediones Ia and Ib to the polarized C=C bond in alkyl vinyl ethers IIa and IIb. 152°C. IR spectrum, ν, cm: 1725, 1690. H NMR spectrum, δ, ppm: 1.18 t (3H, CH3, J = 6.8 Hz), 2.04 s (3H, CH3), 2.06 s (3H, CH3), 2.18 s (3H, CH3), 2.27 s (3H, CH3), 2.38 d.d (1H, 7-H, J = 12.8, 9.6 Hz), 2.96 d.d (1H, 7-H, J = 12.8, 4.2 Hz), 3.77 m (1H, OCH2) 3.81 s (3H, OCH3), 3.94 m (1H, OCH2), 5.64 d.d (1H, CH, J = 9.6, 4.2 Hz), 6.95–7.29 m (10H, Harom). Found, %: C 73.39; H 6.18; N 2.63. C33H33NO6. Calculated, %: C 73.45; H 6.16; N 2.70. 6-Butoxy-7a-(4-methylbenzoyl)-1,4-bis(4-methylphenyl)-1,2,3,6,7,7a-hexahydropyrano[4,3-b]pyrrole-2,3-dione (IIIb) was synthesized in a similar way. Yield 78%, mp 150–151°C. IR spectrum, ν, cm: 1720, 1684. H NMR spectrum, δ, ppm: 0.92 t (3H, CH3, J = 7.2 Hz), 1.39 m (2H, CH2), 1.60 m (2H, CH2), 2.31 s (3H, CH3), 2.37 s (3H, CH3), 2.41 s (3H, CH3), 3.04 d.d (1H, 7-H, J = 12.4, 4.8 Hz), 3.35 d.d (1H, 7-H, J = 12.4, 8.8 Hz), 3.78 m (1H, OCH2), 4.03 m (1H, OCH2), 5.80 d.d (1H, 6-H, J = 8.8, 4.8 Hz), 6.97–7.72 m (12H, Harom). Found, %: C 75.74; H 6.31; N 2.61. C33H33NO5. Calculated, %: C 75.69; H 6.35; N 2.67.

Synthesis and mesomorphic properties of oxadiazole esters derived from (R)‐2‐octanol, (S)‐2‐n‐octyloxypropanol and (2S,3S)‐2‐chloro‐3‐methylpentanol

A novel series of chiral liquid crystalline materials based on 1,3,4‐ and 1,2,4‐oxadiazole derivatives were synthesised. These compounds contain a chiral chain derived from (R)‐2‐octanol (Ia–Ic), (S)‐ethyl lactate (IIa–IIc) or (S)‐isoleucine (IIIa–IIIc). Their liquid crystalline properties were studied by polarizing optical microscopy and differential scanning calorimetry. With the exception of compounds IIa and IIb, all of the new compounds exhibit an enantiotropic chiral nematic (cholesteric) phase. A monotropic chiral smectic C phase (ferroelectric) was also found in compounds Ia, IIa and IIb, whereas in compound IIIa an enantiotropic chiral smectic C phase was observed. Compounds Ic, IIc, IIIb and IIIc are purely chiral nematic (cholesteric) in character. In addition, a monotropic blue phase was observed in compounds Ib and IIIa.

Nucleophilic [3+3]-addition of N-Unsubstituted enamine to monocyclic 1H-Pyrrole-2,3-diones

A reaction is described of substituted 1H-pyrrole-2,3diones (methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1Hpyrrole-2-carboxylates) with N-alkyland N-arylsubstituted 3-amino-5,5-dimethyl-2-cyclohexen-1-ones providing 1-alkyland 1-aryl-susbtituted 6,6-dimethyl2,4-dioxo-2,3,4,5,6,7-hexahydro-1H-indole-3-spiro2'-(1'-aryl-3'-aroyl-4'-hydroxy-5'-oxo-2',5'-dihydro1'H-pyrroles) [1, 2]. The reaction proceeds as successive attacks of β-CH and NH groups of the enamino fragment of the carbocyclic enamines first on the carbon atom in the position 2 and then on the carbonyl group of the methoxycarbonyl moiety (substituent in the position 2) of pyrrolediones followed by methanol elimination. In reaction of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5dihydro-1H-pyrrole-2-carboxylates Ia and Ib with N-unsubstituted 3-amino-5,5-dimethyl-2-cyclohexen-1-one (II) taken in a ratio 1:1 performed by boiling in anhydrous benzene for 1–2 min (to the disappearance of the bright red color of initial compounds Ia and Ib) we unexpectedly obtained methyl 11-aryl-12-benzoyl-9-hydroxy-5,5dimethyl-3,10-dioxo-8,11-diazatricyclo[7.2.1.02,7]dodec2(7)-ene-1-carboxylates IIIa and IIIb. Spectral characteristics of compounds IIIa and IIIb are close to those of a model substituted 3,10,13-triazapentacyclo[10.7.1.01,10.04,9.014,19]eicosa-4,6,8,14(19)-tetraene, whose structure was confirmed by XRD analysis [3]. Evidently the bridged compounds IIIa and IIIb formed by the addition of β-CH and NH2 groups of the enamino fragment of carbocyclic enamine II to atoms C2 and C4 respectively of monocyclic pyrrolediones Ia and Ib.

Antimicrobial Evaluation of Some Mannich Bases of Acetophenones and Representative Quaternary Derivatives.

1-Aryl-3-dimethylamino-1-propanone hydrochlorides Ia-f (series I) as mono-Mannich bases bis (β-aroylethyl) ethylamine hydrochlorides IIa, IIb, IId, IIe (series II) as bis-Mannich bases, 3-aroyl-4-aryl-1-ethyl-4-piperidinol hydrochlorides (structural isomer of bis derivatives IIIa-e, series III), and some of their representative quaternary salts (Ig, IIIf, IIIg) were synthesized. Antimicrobial activities of the compounds were evaluated against some bacteria and fungi. Series I and III showed antimicrobial activity against gram positive bacteria. All series demonstrated activity against fungi, however, they generally did not affect gram negative bacteria at the concentration range tested (2–64 µg/ml). Quaternisation procedure improved the bioactivity in compound IIIa for antibacterial activity and in compounds IIIa and IIIb for antifungal activity against Trichophyton rubrum and Mycosporium canis. There was no relationship between Hammett values of the aryl substituents and bioactivities in series III. The mono-Mannich bases of series I had better antimicrobial activities than bis-Mannich bases of series II. Compounds Ia, If, IIId had equal and compounds If and IIIf had higher antibacterial activities compared to the reference drug, streptomycin (CAS 57-92-1), against various gram positive bacteria. On the other hand, compounds Ia, IIIa, IIIc, IIIe, IIIf, and IIIg had equal and If, IIId, IIIf, IIIg had higher antifungal activity compared to the reference drug, amphotericin-B (CAS 1397-89-3), against various fungi. To conclude, the compounds of series III, having both marked antifungal and antibacterial activities, may serve as candidate compounds for further studies. Especially compound IIIf may serve as a model compound to develop new agents against dermatophytes.

New Synthesis of 5-Aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

The acylation of 4,5-dihydro-1,2,4-triazole-5thiones with carboxylic acid chlorides is known to occur at the nitrogen atom in position 1 of the heteroring [1, 2], while compounds having an activated double bond readily add at the 5-thioxo group at 20oC [3]. Taking these data into account, we proposed a new procedure for synthesizing poorly studied 5-aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of triazolethione I with substituted cinnamoyl chlorides IIa3IIc (Scheme 1). The heterocyclization occurs under mild conditions, on heating the reactants in a benzene3pyridine mixture for 1 h under reflux. Products III were formed in good yields, and no by-products were detected. The structure of compounds III was established on the basis on the H NMR spectra. The double bond of initial cinnamoyl chloride II (two doublets at d 6.80 and 7.50 ppm) is transformed into a single bond (d 3.3035.50 ppm) which gives rise to an ABX system. The composition of products III was confirmed by the data of mass spectrometry and elemental analysis. 5-Phenyl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one (IIIa). A solution of 1.66 g (10 mmol) of cinnamoyl chloride (IIa) in 4 ml of benzene was added at 20oC to a solution of 1.01 g (10 mmol) of 4,5-dihydro-1,2,4-triazole-5-thione (I) in 4 ml of pyridine. The mixture was refluxed for 1 h, cooled, and diluted with 50 ml of water. The precipitate was filtered off and dried. Yield 1.62 g (70%), mp 163oC. H NMR spectrum (acetone-d6), d, ppm: 3.47 m (1H, 6-H), 3.88 m (1H, 6-H), 5.40 m (1H, 5-H), 7.4637.58 m (5H, Harom), 8.10 s (1H, 2-H). Mass spectrum, m/z (Irel, %): M + . 231 (27). Found, %: C 56.66; H 3.95; N 18.20. C11H9N3OS. Calculated, %: C 57.14; H 3.89; N 18.18. Compounds IIIb and IIIc were synthesized in a similar way. 5-(4-Methoxyphenyl)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one (IIIb). Yield 72%, mp 143oC. H NMR spectrum (acetone-d6), d, ppm: 3.41 m (1H, 6-H), 3.78 m (1H, 6-H), 3.83 s (3H, CH3O), 5.36 m (1H, 5-H), 7.00 d (2H, Harom), 7.53 d (2H, Harom), 8.06 s (1H, 2-H). Mass spectrum, m/z (Irel, %): M + . 261 (41). Found, %: C 55.12; H 4.10; N 16.12. C12H11N3O2S. Calculated, %: C 55.17; H 4.21; N 16.09. 5-(3-Nitrophenyl)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one (IIIc). Yield 81%, mp 202oC. H NMR spectrum (DMSO-d6), d, ppm: 3.41 m (1H, 6-H), 3.99 m (1H, 6-H), 5.60 m (1H, 5-H), 7.76 d.d (1H, Harom, J = 8.3, J` = 8.3 Hz), 7.95 d (1H, Harom, J = 8.3 Hz), 8.25 d (1H, Harom,

ChemInform Abstract: Synthesis of syn-3a(12c),9a(9b)-Dihomoperylene-3,10-dione, (E)-syn-2,2′-Bi(7H-1,6-methano[10]annulenylidene)-7,7′-dione and of Its Rearrangement Product, trans-12a,12b-Dihydro-3a(12c),9a(9b)-dihomoperylene-3,10-dione.

The main objective of the present work was to evaluate the synthesis of 1,6-methano[10]annulene derivatives of perylene and perylene-3,10-dione. The starting material for the synthetic sequence was 2,7-dibromo-1,6-methano[10]annulene (I), which was converted by methoxy- and ethoxy-debromination SNAr-type reactions to 2-bromo-7-methoxy- and -7-ethoxy-1,6-methano[10]annulenes (II). The reactions were much more facile than those of the apparently similar halogenonaphthalenes. Compounds II were reductively coupled, using a Ni(0) complex, to give isomeric mixtures of rac- and meso-7,7-dimethoxy- and -diethoxy-2,2′-bi(1,6-methano[10]annulenyl)s (IIIA and IIIB). Oxidative coupling of a mixture of compounds IIIA and IIIB with thallium(III) trifluoroacetate in acetonitrile gave (E)-syn-2,2′-bi(7H-1,6-methano[10]annulenylidene)-7,7′-dione IV as the main reaction product, accompanied by a small amount of syn-3a(12c),9a(9b)-dihomoperylene-3,10-dione, VI. Subsequent experiments showed that the meso-form (IIIB) produced the syn-dihomoperylenedione (VI); while the rac-form (IIIA) gave (E)-syn-2,2′-bi(7H-1,6-methano[10]annulenylidene)-7,7′-dione IV. The low yield of the dihomoperylenedione suggests decomposition reactions occur, with various by-products remaining undetected. A solution of the annulene-quinone (IV) in carbon tetrachloride, when refluxed and illuminated rearranged to give trans-12a,12b-dihydro-3a(12c),9a(9b)-dihomoperylene-3,10-dione (V).

Synthesis of syn-3a(12c),9a(9b)-dihomoperylene-3,10-dione, (E )-syn-2,2′-bi(7H-1,6-methano[10]annulenylidene)-7,7′-dione and of its rearrangement product, trans-12a,12b-dihydro-3a(12c),9a(9b)-dihomoperylene-3,10-dione

The main objective of the present work was to evaluate the synthesis of 1,6-methano[10]annulene derivatives of perylene and perylene-3,10-dione. The starting material for the synthetic sequence was 2,7-dibromo-1,6-methano[10]annulene (I), which was converted by methoxy- and ethoxy-debromination SNAr-type reactions to 2-bromo-7-methoxy- and -7-ethoxy-1,6-methano[10]annulenes (II). The reactions were much more facile than those of the apparently similar halogenonaphthalenes. Compounds II were reductively coupled, using a Ni(0) complex, to give isomeric mixtures of rac- and meso-7,7-dimethoxy- and -diethoxy-2,2′-bi(1,6-methano[10]annulenyl)s (IIIA and IIIB). Oxidative coupling of a mixture of compounds IIIA and IIIB with thallium(III) trifluoroacetate in acetonitrile gave (E)-syn-2,2′-bi(7H-1,6-methano[10]annulenylidene)-7,7′-dione IV as the main reaction product, accompanied by a small amount of syn-3a(12c),9a(9b)-dihomoperylene-3,10-dione, VI. Subsequent experiments showed that the meso-form (IIIB) produced the syn-dihomoperylenedione (VI); while the rac-form (IIIA) gave (E)-syn-2,2′-bi(7H-1,6-methano[10]annulenylidene)-7,7′-dione IV. The low yield of the dihomoperylenedione suggests decomposition reactions occur, with various by-products remaining undetected. A solution of the annulene-quinone (IV) in carbon tetrachloride, when refluxed and illuminated rearranged to give trans-12a,12b-dihydro-3a(12c),9a(9b)-dihomoperylene-3,10-dione (V).

Synthesis of 5-propynyloxycycloalkanepyrimidines and their selectivity and reactivity in intramolecular Diels-Alder reactions.

The 5-propynyloxycycloalkane pyrimidines IIIA ( 17 – 20), IIIB ( 21 – 24), and IIIC ( 25, 26) and the 5-(1-propynyloxyethyl) pyrimidines IIID ( 27,28), easily undergo intramolecular Diels-Alder reactions with inverse electron demand and a subsequent retro Diels-Alder reaction in which R 1CN (R 1 = H, Me) or X-CH 2CN (X = −CH 2, −CH 2CH 2, −H) is expelled. For the compounds IIIA and IIIB the extrusion of X-CH 2CN is favoured, yielding 3-(3-cyanopropyl)-1,3 dihydro-6-phenyl-R 1-R 2-furo[3,4- c ]pyridines ( 29 – 36). The compounds 17 and 21 also yielded 4-phenyl-2 H-6,7,8,8a-tetrahydro-furo[4,3,2- de ]quinoline ( 38), by expulsion of HCN or MeCN respectively, which constitute a new class of heterocyclic compounds. For the compounds IIIC and IIID the extrusion of HCN is favoured as compared to the extrusion of X-CH 2CN. In case of IIIC this also gives a hitherto unknown class of heterocyclic ring systems namely 2 H- 1,6,7,8,9,9a-hexahydro-4-phenyl-9a-R 1-5-aza-1-oxo-benz[ c , d ]azulenes ( 39, 40). The reactivity of the compounds III towards the cycloaddition appears to be strongly influenced by the nature of the substituent R 2 if R 1 = H. However, if R 1 = Me the effect of R 2 on the reactivity was very small. The ratio of the products V and VI appears to depend mainly on the nature of -X-.

Dimethylaminomethylene protected purine H-phosphonates in the synthesis of biologically active RNA (24-mer)

Preparation of 5’-O-(4,4’-dimethoxytrityl)-2’-O-tert-butyldimethylsilyl (tBDMSi) derivatives of N2-dimethylaminomethyleneguanosine (IIIa) and N6-dimethylaminomethyleneadenosine (IVa) and their 3’-H-phosphonates (IIIb, IVb) is described. The compounds IIIb and IVb together with corresponding derivatives of uridine (Vb) and N4-benzoylcytidine (VIb) were used as synthones in machine assisted synthesis of microhelixAla (5’-GGGGCUAUAGCUCUAGCU.CCACCA-3’) (X). The compound X was aminoacylated by means of alanyl-t-RNA synthetase (E.coli).

Kinetics and mechanism of solvolysis of N-aryl sulfuric diamides

The methanolysis and hydrolysis kinetics have been studied with the following sulfuric diamide derivatives: N-methyl-N-phenyl- (IIIa), N-methyl-N-(4-methoxycarbonylphenyl)- (IIIb), N-(4-methoxycarbonylphenyl)- (IIIc), N-methyl-N-(2-methoxycarbonylphenyl)- (IIId), N-(2-methoxycarbonylphenyl)- (IIIe), and N-methyl-N-(2,4-dibromophenyl)- (IIIf). The solvolyses of the neutral substrates IIIa and IIIb proceed by the addition-elimination mechanism. In the presence of the solvent lyate ions the solvolyses go by the E1cb mechanism. The solvolyses of the conjugated bases of compounds IIIa and IIIb are subject to general acid catalysis, the effects of the ring substituents being opposite to those in the addition-elimination mechanism. The solvolyses of compounds IIId and IIIf exhibit a distinct catalytic effect of neighbouring group; the reaction goes via a reactive intermediate, the transformation of the intermediate into the solvolysis product being subject to general acid and base catalysis.

Potential antidepressants. Synthesis of 6,11-dihydrodibenzo[b,e]thiepin-11-yl (dimethylaminomethyl)phenyl ethers, sulfides, amines and some related compounds

Reactions of 11-chloro-6,11-dihydrodibenzo[b,e]thiepin and its 2-bromo derivative with the isomeric (dimethylaminomethyl)phenols, (dimethylaminomethyl)thiophenols, and (dimethylaminomethyl)anilines in toluene afforded the title compounds IIIb,c, Va, VIIIa,b,c, and Xa,b,c. Reactions of 11-chloro-6,11-dihydrodibenzo[b,e]thiepin and its 2-chloro and 2-methyl derivatives with N,N-dimethyl-2-(4-aminophenoxy)ethylamine and N,N-dimethyl-3-(4-aminophenoxy)propylamine by heating in dimethylformamide in the presence of sodium carbonate gave the diamino ethers XI-XIV. The compounds showed only indications of the antidepressant agents profile and some antimicrobial effects in vitro.

On some copper(I) perthiocarboxylates and their reactions with tertiary phosphines. Crystal structure of tetra( p-tolyldithiocarboxylato)tetracopper(I), [CuS 2C- p-tolyl] 4, and of [bis(triphenylphosphine)( p-tolyldithiocarboxylato)copper(I)] triphenylphosphine sulfide, [CuS 2C- p-tolyl(PPh 3) 2]·PPh 3S

Some copper(I)perthiocarboxylates [CuS 3CAr] 4 ( I) ( Ia, ArPh; Ib, Ar p-tolyl) were prepared in high yields from the corresponding aldehydes and ammonium polysulfide in basic medium. By reacting them with triphenylphosphine in different ratios, formation of PPh 3S occurred and the following series of products could be isolated: [(CuS 3CAr) 2(CuS 2- CAr) 2]py 2 ( II); [CuS 2CAr] 4 ( III); [(CuS 2CAr) 4- (PPh 3) 2] ( IV); [CuS 2CAr(PPh 3) 2] ( V). In the case of p-tolyl the complex [CuS 2CAr(PPh 3) 2]·PPh 3S ( VIb) was also obtained. Some significant IR and NMR ( 13C, 31P) data of the above compounds are reported. The crystal structures of compounds IIIb and VIb were established by single crystal X-ray diffraction methods. Crystals of IIIb are triclinic, space group P 1 , with a=13.879(4), b=10.324(3), c=13.479(4) Å,α=99.04(2), β=113.31(3), γ= 92.34(2)° and Z=2. Crystals of VIb are also triclinic, space group P 1 , with a=15.833(5), b= 10.999(3), c=15.690(5) Å, α=103.12(3), β= 90.88(2), γ=94.05(2)° and Z=2. The structures have been solved by direct and Fourier ( IIIb) and by Patterson and Fourier ( VIb) methods and refined by blocked full-matrix least-squares to R=0.059 for IIIb and R=0.051 for VIb. The structure of IIIb consists of discrete units of four copper atoms bound to sulfur atoms from four p-tolyldithiocarboxylate groups acting as tridentate ligands. A sulfur atom of each ligand coordinates to one only copper atom and the other bridges two adjacent metals so that each metal is pseudo-trigonally surrounded by three sulfur atoms. In the structure of VIb monomeric complexes are present in which the metal atom is pseudo-tetrahedrally coordinated by two phosphorous atoms from triphenylphosphine ligands and by two sulfur atoms from one chelating p-tolyldithiocarboxylate group. Triphenylphosphine sulfide molecules are also present in the crystals of VIb. The complex autoxidative reactions of some dithiocarboxylates in pyridine, which cause a partial transformation of the sulfur atoms in coordinated ‘SO 4’ groups, were also investigated.

Potential antidepressants: 2-(Aminoalkoxy)biphenyls and some related ω-substituted 2-alkoxybiphenyls

Reactions of 2-hydroxybiphenyl with α,ω-dibromoalkanes gave the 2-(bromoalkoxy)biphenyls IIIa-IIId. The 2-(dimethylaminoalkoxy)biphenyls VIa and VIb were transformed via carbamates VIIa and VIIb to the secondary amines Va and Vb. Their homologues Vc and Vd were obtained from the bromo compounds IIIc and IIId by treatment with methylamine. Bromo compounds IIIa and IIIb were reacted with 1-methylpiperazine, 2-(1-piperazinyl)ethanol, 3-(1-piperazinyl)propanol, and 4-amino-1-benzylpiperidine and gave the diamines VIIIa, VIIIb, IXa, Xa, Xb, and XIa. Addition of 2-hydroxybiphenyl to acrylonitrile afforded the nitrile XIIa. The homologous nitrile XIIb was obtained from the bromo compound IIIb and sodium cyanide in dimethyl sulfoxide. Nitriles XIIa and XIIb were reduced with aluminium hydride to diamines IVb and IVc. The nitriles were also transformed to hydrochlorides of the corresponding ethyl imidates XIVa and XIVb. Their hydrolysis resulted in the esters XVa and XVb. The acid XIIIa was obtained by acid hydrolysis of the nitrile XIIa; the acid XIIIb resulted from the acid hydrolysis of the ester XVb. The imidate XIVb was transformed to the amidine XVIb and to the dihydroimidazole XVIIb. Only the amine Vc showed properties indicative of potential antidepressant.

Reaction of 6-azauridine with thionyl chloride in hexamethylphosphoramide

Reaction of 6-azauridine (I) with a mixture of thionyl chloride and hexamethylphosphoramide afforded 5'-chloro-5'-deoxy-6-azauridine (II) and a mixture of SR- and SS-isomers of 5'-chloro-5'-deoxy-2',3'-O-sulfinyl-6-azauridine (IIIa and IIIb) which were separated by column chromatography on silica gel; compounds IIIa and IIIb also arose in the reaction of compound II with diphenyl sulfite. Removal of the cyclic sulfinyl group from the isomeric sulfites IIIa and IIIb gave compound II; reaction of IIIa and IIIb with imidazole in dimethylformamide afforded the 5'-chloro-5'-deoxy-2,2'-anhydro derivative IV.

Übergangsmetalkoordinierte Heteroolefine als Synthesebausteine: Einfluss des Alkins auf die Geschwindigkeit und die Stereoselektivität der Reaktion mit Heteroaldehyd- bzw. -keton-Komplexen

Pentacarbonyl-(-thio- and -seleno-aldehyde) complexes and pentacarbonyl(diphenylselenoketone) complexes, (CO) 5M[XC(Ph)R] (M  W: X  S, R  H (Ia); X  Se, R  H (Ib); X  Se, R  Ph (Ic); M  Cr: X  Se, R  Ph (Id)), react with bis(diethylamino)acetylene, Et 2NcCNEt 2 (II) by [2 + 2]-cycloaddition of the alkyne to the XC bond of I, and with electrocyclic ring opening to give the pentacarbonyl-(-thio- and -seleno-acrylamide) complexes, (CO) 5M[XC(NEt 2)C(NEt 2)C(Ph)R] (III). If R  H, ring opening is stereospecific. According to the NMR spectra, only the E isomer (with respect to the CC double bond) is formed. Compounds IIIa and IIIb were studied by X-ray crystallography. The plane of the amido group, XC(N)C, is almost perpendicular to that of the olefin, C(N)CC. The reaction of Ic with II in 1,1,2-trichloroethane follows second-order kinetics: −d[Ic]/d t = k 2[Ic][II]. The activation enthalpy Δ H * is small (27(2) kJ/mol), and the activation entropy Δ S * is strongly negative (−164(8) J/(mol K)). Cleavage of the CrSe Bond in IIId is achieved by applying a CO pressure (105 bar) at 70°C and the selenoacrylamide SeC(NEt 2)C(NEt 2)CPh 2 is isolated in almost quantitative yield.