Reduction of the 1,2,5-thiadiazole ring of 3,6:12,15-di-1,4-benzo[6.6](3,4)-1,2,5-thiadiazolo- and 3,5:11,13-di-1,3-benzo-[6.6](3,4)-1,2,5-thiadiazolocyclophanes. Selective preparation of cis- and trans-[23]cyclophane-1,2-diacetoamide

The effect of the [2.2.2]cyclophane ring structure on the reduction of 1,2,5-thiadiazole ring incorporated in cyclophanes 1a-c and 2a-c was investigated. When reduced by sodium metal in ethanol followed by acetylation, para[2³]cyclophane 1 gave a mixture of the expected cis- and trans-diamides, 3 and 4 , in which 4 was the major product. On the other hand, reduction of 1 with lithium aluminum hydride proceeded in a cis-selective manner and gave 3 as a major product after a treatment of the reduced products with acetic anhydride. The reduction of metacyclophane 2 , which is less strained than 1 , proceeded exclusively in cis-fashion and a subsequent treatment of the reduction product with acetic anhydride gave only cis-diamide 6 .     

Cation radicals. XXXII. Reaction of N-ethylcarbazole with iodine-silver salts. Nitration of N-ethylcarbazole

Reaction of N-ethylcarbazole ( 1 ) with iodine-silver perchlorate gave a green solution having a singlet esr signal. Reduction of the solution with potassium iodide gave N,N′ -diethyl-3,3′-dicarbazolyl ( 3 , 48%). Small amounts of 3-iodo- ( 4 ) and 3,6-diiodo-N-ethylcarbazole ( 5 ) were also obtained. Compounds 4 and 5 are believed to have been formed by electrophilic iodination of 1 by I₂-AgCIO₄, whereas 3 appears to have been formed via the dimerization of 1 ^.+. In accord with this, reaction of 1 with iodine-silver nitrite gave 3-nitro-N-ethylcarbazole ( 6 , 61%), 9% of another nitro-N-ethylcarbazole ( 7 ), thought to be either 1- or 4-nitro-N-ethylcarbazole, and 28% of 4. Thus, trapping of 1 ^.+ by nucleophilic nitrite ion occurred even though 1 ^.+ is not stable enough toward isolation as the perchlorate.     

Intramolekulare Diels-Alder-Additionen in 6-(But-3-enyl)-6-methyl-cyclohexa-2,4-dien-1-on-Systemen; eine neue Synthese von Twistanderivaten

Alkylation of the sodium salt of mesitol with 2-bromomethyl-buta-1,3-diene ( 7 ) in benzene and subsequent refluxing of the reaction mixture gave 7% 2-methylene-3-butenyl-mesitylether ( 8 ), 12% 5-methylene-1,3,8-trimethyl-tricyclo[4,3,1,0^3,7]-8-decen-2-one ( 9 ) and 44% 9-methylene-1,3,5-trimethyl-tricyclo[4,4,0,0^3,8]-4-decen-2-one ( 10 ), a twistane derivative. The same procedure, when applied to the sodium salt of 2,6-dimethyl-4-methoxyphenol, gave in 73% yield a 26:18:54 mixture of 2,6-dimethyl-4-methoxyphenyl-(2-methylene-3-butenyl)-ether ( 11 ), 1,3-dimethyl-8-methoxy-5-methylene-tricyclo[4,3,1,0^{3, 7}]-8-decen-2-one ( 12 ), and 1,3-dimethyl-5-methoxy-9-methylene-tricyclo[4,4,0,0^{3, 8}]-4-decen-2-one ( 13 ). The tricyclic ketones 9 and 10 , or 12 and 13 , were also obtained on heating 8 or 11 respectively at 176° in decane solution. Alkylation of the sodium salt of 2,6-dimethylphenol with 3-butenylbromide in boiling toluene gave 1,3-dimethyl-tricyclo[4,3,1,0^3,7]-8-decen-2-one ( 17 ) as the only tricyclic product in 8% yield. The structures of the twistane derivatives 10 and 13 as well as those of the ketones 9, 12 and 17 were mainly deduced from spectroscopic data. Furthermore, the ketones 10 and 13 could be converted to the twistane derivatives 20 and 22 , possessing C₂-symmetry. On the other hand, compounds 9 and 17 gave only the asymmetric derivatives 18 and 21 .     

Synthesis and characterization of azidated Adenopus breviflorus benth seed oil

ABSTRACT

Azidation of plant seed oils was re-investigated using methods reported in the literature, to re-examine if triacylglycerol backbone, important for maintaining biodegradability in plant oil products is retained in the final azidated oil. Reaction of NaN₃ with epoxidized Adenopus breviflorus oil (EADBO) using NH₄Cl as catalyst (Method A), gave acidolysis products and mixture of products containing triacylglycerol backbone. Reaction of EADBO with NaN₃ in water using an ionic liquid, 1-methyl imidazolium tetrafluoroborate ([Hmim]BF₄ ^?), as catalyst (Method B), generated a product containing only triacylglycerol backbone while product of reaction of EADBO with NaN₃ in DMF, using [Hmim]BF₄ ^? catalyst (Method C) gave highest yield but did not contain any triacylglycerol backbone. Thus, Method B was best for environmentally friendliness of its azidated product. Azido compounds generally prepared from petrochemicals may now be prepared from plant oil source using method B for preparation of biodegradable vicinal hydroxyl triglyceride which is very versatile in surfactant industries.     

Electrochemical Chlorination of Physcion – An Approach to Naturally Occurring Chlorinated Secondary Metabolites of Lichens

The electrochemical chlorination of physcion (=1,8‐dihydroxy‐3‐methoxy‐6‐methylanthracene‐9,10‐dione; 1 ) in AcOH and CH₂Cl₂ was investigated by cyclic voltammetry and prep.‐scale electrolysis. This approach provided access to a number of diverse biologically and pharmacologically interesting chlorinated secondary metabolites of lichen. Unlike the only previous literature report on the ‘classical’ chlorination of physcion ( 1 ), which allowed the preparation of 4‐chlorophyscion ( 2b ), 4,5‐dichlorophyscion ( 3b ), and 2,4,5‐trichlorophyscion ( 4 ), the present procedure also gave fragilin (=2‐chlorophyscion; 2a ) and 2,4‐dichlorophyscion ( 3a ), alongside the previously obtained 2b, 3b , and 4 . All of these compounds, except for 2a , were isolated by column chromatography and medium‐pressure liquid chromatography (MPLC) and characterized by spectral data. The preparative electrolysis with a 2 F?mol^?1 charge consumption in AcOH and 10 F?mol^?1 in CH₂Cl₂ may have a practical synthetic utility, since the thus obtained product mixtures can be readily fractioned by column chromatography to afford pure 2b and 4 , respectively. The regioselectivity of the reaction is explained by the resonance stabilization of the corresponding arenium cations ‐ potential products of an electrophilic attack of a ‘positive’ Cl species on the physcion molecule.     

Investigation of routes to indeno[2,1-f] -2H-1,2,4-triazepinediones

The synthesis of a number of 3-(substituted thiosemiearbazido)-2-(a]koxycarbonyl)indones (1) from 2-alkoxycarbonyl-1, 3-indandiones and substituted thiosemicarbazides is described. Cyeliza-tion of compounds 1 in the presence of a variety of catalysts gave substituted Δ²-1,2,4-triazoline-5-thiones (³) and (⁴), instead of the expected substituted 3(4H)-thioxoindeno[2,1-f]-2H-1,2,4-triazepine-5(5aH),6-diones (2). The preparation of 4-(2-methyl-1,3-dioxo-2-indanylmethyl)semi-carbazide ( 9 ) is reported. Cyelization of 9 gave 5,5a-dihydro-5a-methylindeno[2,1-f]-2H-1,2,4-triazepine-3(4H),6-dione ( 10 ). Structure assignments of these compounds are discussed.     

Synthesis of nitrogen-containing heterocycles. 4. A facile route to new 1, 2, 4-triazole derivatives

The reaction of amino-N(4),N(4)-dimethylaminornethylenehydrazones 1 of some aliphatic carbonyl compounds with ethyl ethoxymethylenecyanoacetate 2 gave directly symmetrical gem-bis(3-dimethylamino-1, 2, 4-triazol-1-yl)alkanes 4 and (3-dimethylamino-1, 2, 4-triazol-1-yl)alkenes 5 at room temperature, with the former being major product. On the other hand, the reaction of amino- N (4)-methylaminomethylenehydrazone homologue 1 of aliphatic ketone with 2 gave ethyl 2-alkyl-5-methylamino[1, 2, 4]triazolo[1, 5-c]pyrimidine-8-carboxylate 7 as the only product with elimination of alkane.     

Triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcones: Synthesis of 3-(2-aminoethylthio)-1-(aryl)-3-(thiophen-2-yl) propan-1-ones and 5,7-diaryl-2,3,6, 7-tetrahydro-1,4-thiazepines

The triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcone analogs was investigated. This addition, bearing a 2-thienyl group at the 3-position, gave the only addition adduct at room temperature in 3 h, whereas the chalcones bearing the 2-furyl group at the 1-position gave an addition-cyclization product (1, 4-thiazepine) in the same conditions. The effect of the groups to the reaction was investigated by changing the 1- and 3-position groups. The chalcones bearing the 2-thienyl group at the 1-position and the others afforded the mixture of products in different ratio at rt for 0.5–24 h. Moreover, the addition–cyclization products (1,4-thiazepine) were obtained under reflux conditions in 36 h. The structures of the synthesized compounds were elucidated by ¹H NMR, ¹³C NMR, infrared, and elemental analysis.     

Synthesis of the 2,5-dioles of A-nor-5-alpha-cholestanes and A-nor-5-beta-cholestanes

Treatment of A-nor-Δ³⁽⁵⁾-cholestene-2-one ( 1 ) with alkaline hydrogen peroxide gave 3β,5-epoxy-A-nor-cholestane-2-one ( 2 ) and the epoxylactone 3 (BAEYER -VILLIGER reaction). LiAlH₄-reduction of 2 yielded A-nor-5β-cholestane-2β,5-diol( 4 ) (main product) and A-nor-5β-cholestane-2α,5-diol ( 5 ). LiAlH₄-reduction of 1 led mainly to A-nor-Δ³⁽⁵⁾-cholestene-2α-ol ( 8 ). Catalytic hydrogenation of 8 gave the known A-nor-5α-cholestane-2α-01 ( 10 ), A-nor-5β-cholestane-2α-01 ( 11 ) (main product), A-nor-5β-cholestane ( 9 ) and A-nor-5β-cholestane-2-one ( 12 ). By LiAlH₄-reduction of the ketones 12 and 13 the two additional alcohols 14 and 15 were obtained.     

Tricyclic heteroaromatic systems. 1,2,3,4-tetrahydropyrazolo[4,3-c][l]benzazepin-1-ones as potential antitumor agents

The synthesis of 1,2,3,4-tetrahydropyrazolo[4,3-c][1]benzazepin-1-ones 1 and that of its 10-methyl derivative 2 is reported. The preparation of the latter from 3-(2-aminobenzyl)3-pyrazolin-5-one and triethyl ortho-formate gave as the main product a derivative of the new tricyclic ring system, pyrazolo[1,5-c][1,3]benzo-diazepine. The structures of the new compounds synthesized were assigned by means of a ¹³C nmr study.     

Competition between singlet state photoreduction and triplet state photodimerization of dimethyl 3-dehydrogibberellenate

Photolysis of dilute solutions (10^-4M) of dimethyl 3-dehydrogibberellenate 1, in MeOH, EtOH, i-PrOH, t-BuOH and 2, 2, 2-trifluoroethanol, showed that while the last two solutions underwent photodimerization reactions only; the other solutions gave photoreduction products 2 and 3, besides some photodimerization product. It is further shown that while photodimerization proceeded through triplet excited state, photo-reduction, surprisingly, proceeded only through singlet excited state.     

Access to 14C-Ring labelled phenothiazines. Synthesis of 2-chlorophenolhiazine-5a,9-14C

Through the use of a recently reported ring expansion reaction, a new route to phenolhiazines has been developed suitable for the preparation of ring labelled derivatives. As an example, the preparation of 2-chloropheno thiazine-5a,9-¹⁴C ( 1 ) is reported. Condensation of cyclohexanone-2-¹⁴C with 2-amino-4-chlorothiophenol gave the spiro-2,3-dihydro-l, 3-benzothiazole 4 which was protected by acetylation ( 5 ). Treatment of 5 with sulfuryl chloride gave the tetrahydro-phenothiazine olefin mixture 6 and 7 which was directly converted to labelled 1 via treatment with DDQ in refluxing benzene followed by hydrolysis of the acetyl group.     

THE CHEMISTRY OF SOME UREIDOBENZENESULFONYL CHLORIDES

Abstract

o-Methoxyphenyl-, N-phenyl-N′,N′-dimethyl, and N-3-acetylphenyl-urea with chlorosulfonic acid gave 4-methoxy-3-ureido, 4-(N′,N′-dimethylureido)-, and N-3-acetylureido-benzenesulfonyl chlorides respectively.

However, attempts to chlorosulfonate phenylthiourea were unsuccessful; the product was the zwitterionic sulfonic acid which did not give the sulfonyl chloride with phosphorus pentachloride.

N-Phenyl-N′-p-tolyl urea by reaction with chlorosulfonic acid afforded the corresponding 4-sulfonyl chloride. N-Phenyl-N′-2-pyridyl- and N-phenyl-N′-2-thiazolyl thioureas reacted similarly. In contrast, N-phenyl-N′-2′-pyridylurea only gave the bis-sulfonyl chloride.

Selected ureido-sulfonyl chlorides have been condensed with hydrazine and sodium azide and some reactions of the sulfonyl azides examined.

Acetylation of phenylurea gave only the N-(3-acetyl)- or the S-acetyl derivative depending on the conditions. Contrary to previous work, it is not considered that the N-(l-acetyl) phenylthiourea is formed.     

Investigation of the reactions of fluorine containing 3-hydrazino-5H-1, 2, 4-triazino[5, 6-b]indoles with ethyl acetoacetate. Synthesis of some novel tetracyclic ring systems

Novel tetracyclic ring systems viz. 3-methyl-1-oxo-12H-1, 2, 4-triazepino[3′,4′:3, 4][1, 2, 4]triazino[5, 6-b]indole ( 4a ) and 3-methyl-5-oxo-12H-1, 2, 4-triazepino[4′,3′:2, 3][1, 2, 4]triazino[5, 6-b]indole ( 5a ), having angular and linear structures respectively, were synthesized by the cyclization of 3-oxobutanoic acid [5H-1, 2, 4-triazino-[5, 6-b]indole-3-yl]hydrazone ( 3a ). However, cyclization of 3b (R = CH_a, R¹ = R² = H) afforded the angular product 4b exclusively. Moreover, cyclization of 3c (R = R³ = H, R¹ = F) yielded 7-fluoro-1-0xo-10H-1, 3-imidazo[2′,3′:3, 4][1, 2, 4]triazino[5, 6-b]indole ( 6c ) and 7-fluoro-3-oxo-10H-1, 3-imidazo[3′,2′:2, 3][1, 2, 4]triazino-[5, 6-b]indole ( 7c ) instead of the expected triazepinone derivatives. Compound 3d (R = R¹ = H, R² = CF₃) also gave an imidazole derivative but only one angular product was obtained. In all these reactions, formation of the angular product involving cyclization at N-4 is favoured. Characterization of these products have been done by elemental analyses, ir, pmr, ¹⁹F nmr and mass spectral studies.     

Synthesis and structure of new 3-pyrazolinylcoumarins and 3-pyrazolinyl-2-quinolones

The reactions of substituted 3-cinnamoyl-4-hydroxycoumarins and 3-cinnamoyl-4-hydroxy-2-quinolones with different phenylhydrazines gave 3-hetaryl-1H-4,5-dihydropyrazoles. The product structures were studied by ¹H NMR spectroscopy and mass spectrometry. 4-Hydroxy-3-pyrazo-linylcoumarins exist in DMSO as two tautomers (4-enol and chromane-2,4-dione), while 4-hydroxy-3-pyrazolinyl-2-quinolones exist only in the enol form. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1479–1486, July, 2008.     

CHOLESTERYL PHOSPHITE AND RELATED COMPOUNDS

Abstract

The preparation of cholesteryl phosphorodichloridite (2) is described; this compound with aniline (2 mol. equiv.) gave the N-phenylphosphoramidochloridite (5) and the latter by condensation with water afforded the N-phenyl-amidophosphite (6).

Similarly the N-phenylphosphoramidochloridite (5) with morpholine gave the morpholidite (7); phenylhydrazine gave the hydrazinophosphite (8) and ethanol the amidoethyl phosphite (9). Cholesteryl phosphorodichloridite (2) by reaction with aniline (4 mol. equiv.) gave the N,N ¹?diphenylphosphorodiamidite (10).

The reaction of cholesteryl phosphorodichloridite (2) with methanol and ethanol are discussed in relation to the analogous reactions with cholesteryl phosphorodichloridate. Boiling ethanol gave cholesterol as the only isolatable product but at room temperature a low yield of the diethylphosphite (11; R=Et) was obtained. The yield of the phosphite was greatly increased in the presence of base. Similarly the dichloridite 2 with boiling water gave cholesterol (1), but at room temperature cholesteryl phosphite 3 was isolated: the mechanistic basis for these different results is briefly discussed.

trans-4-t-Butylcyclohexanol with phosphorus trichloride gave the phosphorodichloridite, which was characterised by conversion to the corresponding N,N ¹?diphenylphosphorodiamidite.     

Lower photoreactivity of 3-methyl-3-(4′-biphenylyl)-t-butene

Direct and sensitized photolyses of 3-methyl-3-(4′-biphenylyl)-1-butene gave 1,1-dimethyl-2-(4′-biphenylyl)cyclopropane as primary product and 2-methyl-4-(4′-biphenylyl)-1-butene as secondary product with quantum yields of 7.6×10^?3 and 5.6×10^?3, respectively. On direct photolysis, the triplet reactant rearranged with a quantum yield of 4.4×10^?3 and is more reactive than the singlet. The exceptionally low photoreactivity shows that the excitation energy is largely localized on the biphenylyl portion but can be delivered to the reaction center slowly.     

Oxidations of 3,6-diamino-1,2,4,5-tetrazine and 3,6-bis(s,s-dimethylsulfilimino)-1,2,4,5-tetrazine

Oxidation of 3,6-diamino-1,2,4,5-tetrazine ( 1 ) with most peracids gave 3,6-diamino-1,2,4,5-tetrazine 1,4-dioxide ( 3 ) as the major product; however, treatment of 1 with peroxytrifluoroacetic acid (PTFA) gave 3,6-diamino-1,2,4,5-tetrazine 1-oxide ( 4 ) as the major product along with a small amount of 3-amino-6-nitro-1,2,4,5-tetrazine 2,4-dioxide ( 5 ). Oxidation of 3,6-bis(S,S-dimethylsulfilimino)-1,2,4,5-tetrazine ( 6 ) with 3-chloroperoxybenzoic acid (MCPBA) gave 3-S,S-(dimethylsulfilimino)-6-nitroso-1,2,4,5-tetrazine ( 7 ), which was oxidized further with dimethyldioxirane to 3-(S,S-dimethylsulfoximino)-6-nitro-1,2,4,5-tetrazine ( 8 ). All attempts to obtain 3,6-dinitro-1,2,4,5-tetrazine ( 2 ) by further oxidation of 7 or 8 failed.     

Reactions of Haloarenes with Thiolate Anions in Tetraglyme: Competition between electron transfer and SNAr mechanisms

The reaction of the bromo-substituted naphthalene 1 with the alkanethiolate anions 2a–b and arenethiolate 2c in tetraglyme gave the corresponding 1-naphythyl thio-ethers 3a–c . Thio-ethers 3a–c were oxidized to the corresponding sulfones 4a–c with m- chloroperoxybenzoic acid. The reaction of the dichloro-substituted anthracene 5a with 2b gave the disubstutution product 6a. The reaction of 9-bromoanthracene 5c with the alkanethiolate 2b gave 6b , whereas the reaction of 5c with the arenethiolate 2c gave a mixture of substitution product 6c and anthracene 7. The observation of the formation of both 6c and 7 is explained by the competition between substitution (S_nAr) and electron-transfer (ET) mechanisms. Consistent with this interpretation, the reaction of the monochloro-substituted 5b , which has a higher-energy σ^* orbital, with 2c gave 6c without the formation of 7. Zn/KOH in tetraglyme was shown to reduce the aryl halides 5b–c and thio-ether 6c to 7 .     

A New Total Synthesis of Bulnesol

Some years ago we began work on a general hydroazulenic sesquiterpene synthesis based on the known photo-ene product (II) of citral (I).¹ The projected key step, the cyclization of an olefinic aldehyde, has been extensively studied in model systems: the stereochemical outcome, and other data, suggest a concerted electrocyclic mechanism with the carbonyl serving as an enophile.² However application of this reaction to model aldehydes yielding the guaiane skeleton were less encouraging. Aldehyde III (R[dbnd]H), obtained from photocitral-A by two successive homologations using cyanide displacement of tosylate, gave at best a 60% yield of cyclized material—a mixture of olefin isomers and hydroxy epimers. Initial attempts to incorporate a group R suitable for later elaboration into the isopropylol side chain common in guaianes were also discouraging.