Isoprene functionalization : E/Z-isomerism of 1-sulfonyl substituted 2-methylbutadienes

The isomeric chlorosulfones 3, 4 and 5 are prepared by 1,4-addition of sulfonyl chlorides to isoprene, Dehydrohalogenation affords the corresponding 2- and 3-methylbutadienyl sulfones in a configuration which is dependent on the configuration of the chlorosulfone. Pure Z-2-methylbutadienyl sulfones 1 are obtained by displacement of primary halides by the Z-sulfinate anion 2. The Z-sulfones 1 are isomerized to E/Z-mixtures. The E/Z-mixtures are separated into their components and the configuration of the isomers is established by the NMR-NOE technique.     

A novel synthesis and herbicidal activity of fluorine-containing pyrazolo[3,4-d]pyrimidin-4-one derivatives

The 6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio-5-(fluoro-substituted)phenyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-ones 6 have been successfully synthesized via a tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 4, aromatic isocyanate, and substituted phenols 2 in 59-69% isolated yields using actonitrile as solvent. These novel compounds 6 could be oxidized to sulfones 7 by hydrogen peroxide in satisfactory yields (57-93%). Their structures were clearly verified by spectroscopic data (IR, ¹H NMR, ¹³C NMR, MS, Elemental analysis or X-ray diffraction crystallography). The results of preliminary bioassay indicated that these compounds possess herbicidal activity against the root of rape and barnyard grass.     

Isoprene functionalisation : Chlorination of C10-isoprenoid sulfones with hexachloro-ethane

Lithiation of the sulfones 1–3 in THF at ?78° with lithium diisopropyl amide (LDA) is regioselective, since deuteration of the α-lithiosulfone 4 results in formation of the α-monodeuteriated sulfone 7. Higher temperature causes an intramolecular 1,4-addition of the lithiated sulfone 4 to the lithiated cyclic sulfone 19 and an intermolecular 1,4-addition of the lithiated sulfones 5 and 6. The cyclisation of Z-sulfone 1 has been used for the isolation of the isomeric E-sulfone 2 from mixtures of 1 and 2. The lithiated sulfones 4–6 are chlorinated with hexachloroethane (HCE). Due to acid/base reactions the α,α-dichlorinated cyclic sulfone 23 and α,α'-dichlorinated butadienyl sulfones 13–15 are formed in small amounts.     

Synthesis of (1R,4E,5S)-4-{[(E)-(azinyl)diazenyl]methylidene}-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones and (1R,4R,5R)-4-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones

4-[(Heteroaryldiazenyl)methylidene] and 4-([1,2,4]triazolo[4,3-x]azin-3-yl) substituted (1R,5R)-4-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones 6/6′ and 7/7′ were obtained in a one-pot transformation of the enamino lactone 2 with hydrazinoazines 3a–g followed by oxidation of the intermediate mixture of isomeric enehydrazines 4/4′ and hydrazones 5/5′ with lead tetraacetate. The oxidation selectivity was dependent on the ratio of isomeric intermediates 4/4′ and 5/5′. Treatment of 7b with lead tetraacetate led to α-acetoxylated compound 11, while bromination of 9b afforded a 1:1 mixture of α-bromination products 12 and 12′, which were separated by medium pressure liquid chromatography (MPLC). The structures of intermediates and products were confirmed by NMR and X-ray diffraction.     

Acetolysis of the trifluoromethanesulphonates of syn-12-hydroxyaldrin and syn-12-hydroxyisodrin and their dihydro derivatives : Reduction in neighbouring double bond participation effected by chlorine substituents

Acetolysis rates of the trifluoromethanesulphonates of two geometric isomers of hexachlorotetracyclo[6.2.1.1^3,6.O^2,7]dodeca-4,9-dien-12-ol (6, 8; syn-12-hydroxyaldrin, syn-12-hydroxy-isodrin) and of two geometric isomers of hexachlorotetracyclo[6.2.1.1^3,6.O^2,7dodec-9-en-12-ol (7,9; syn-12-hydroxy-4, 5-dihydroaldrin, syn-12-hydroxy-4,5-hydroisodrin) have been determined. The results show that neighbouring double bond participation by a —ClCCCl— grouping that is juxtaposed to an incipient secondary carbenium ion (> CH·OSO₂CF₃ is negligible compared with that seen in the non-chlorinated prototypes containing an analogously-situated —CHCH— grouping (e.g.4). The products of acctolysis of 8 and 9 were acetates of the original carbocyclic ring system, but the acctolysis of 6 at 64° yielded, as the sole rearranged product, a hexachloropentacyclo[7.2.1.O^2,8.O^3,5.O⁴]dodecen-6-yl acetatc10. The major products of acetolysis at 64° of 7 were a mixture of two isomeric hexachlorotetracyclol[6.3.1.O^2,9.O^3,7]dodecen-11-yl acetates(17,18) and a hexachloropentacyclo[6.4.0.O^2,10.O^3,7.O^9,11 dodec-4-ene 15; these were each formed via an initial bridging reaction and subsequent rearrangement steps. The factors that dictate the nature of products formed from each compound are discussed, and probable pathways to each are delineated.     

Rearrangement thermique des adduits du tetracyanoethylene de 2H-pyrannes

The addition of tetracyanotehylene to 2H-pyrans 1 results in a mixture of two isomeric adducts 6. The thermal decomposition of the compounds 6 gives rise to both a small percentage of the retro Diels-Alder, and a new mode of evolution leading to a mixture of furans (E+Z) 7. A detailed interpretation of the ¹³C spectra of the compounds 7 was established by comparison with the ¹³C spectra of 2,5-diphenylfuran and trans-stilbene. The structure 7 is confirmed by chemical degradation.     

Interference peaks in collisional activation mass spectra: The loss of CH3˙ from [C13H9] ions

It was concluded from earlier metastable ion and collisional activation experiments that [C₁₃H₉]⁺ ions generated by dissociative ionization of stilbenes and diphenylmethane consist of a mixture of isomeric structures. It is shown in this paper that the methyl loss upon which this conclusion rests originates to a large extent from metastable molecular ions decomposing in the magnetic sector field (interference signal). Our results do not show, nor do they require, that more than one isomeric [C₁₃H₉]⁺ species is present. The importance of recognizing such interference signals is stressed.     

Studies on organophosphorus compounds—XXVIII: Syntheses of 3H-1,2-dithiole-3-thiones and 4H-1,3,2,-oxazaphosphorine derivatives from the dimer of p-methoxyphenyl-thionophosphine sulfide and der

Unsubstituted and 2-monosubstituted 3-oxo esters react with the dimer of p-methoxyphenyl-thionophosphine sulfide (1) and elemental sulfur in anhydrous toluene at 110° to give the corresponding 3H-1,2-dithiole-3-thiones (2) in nearly quantitative yields (90–95%). Ethyl 2,2-dimethyl 3-oxo-butanoate, failing to react in toluene at 110°, decomposes into a complex mixture at 140° in anhydrous xylene. Also secondary and tertiary 3-oxo-amides such as acetoacetanilide and N,N-dimethylacetoacetamide produce the corresponding 3H-1,2-dithiole-3-thiones (2) upon treatment with 1 and elemental sulfur. Primary 3-oxo-amides and 3-oxo-nitriles react with 1 in anhydrous toluene at 110° giving in all cases investigated, derivatives of 2,3-dihydro-2(4-methoxyphenyl)-4H-1,3,2-oxazaphosphorine-4-t as main products (70–95%). ¹H, ¹³C and ³¹P NMR data are tabulated and reaction mechanisms are suggested.     

Synthesis of new sulfanyl-, sulfinyl-, and sulfonyl-substituted polychlorobuta-1,3-dienes

New R-sulfanyl-substituted polychlorobuta-1,3-dienes were synthesized by reactions of hexachloro-1,3-butadiene or 1,1,2,4,4-pentachlorobuta-1,3-diene with dimethylbenzenethiols, heptane-1-thiol, and 4-methyl-7-sulfanyl-2H-chromen-2-one. Some sulfides were oxidized to the corresponding sulfoxides and sulfones or brominated with bromine. Among the synthesized compounds, the coumarin derivative, 4-methyl-7-(1,2,3,4,4-pentachlorobuta-1,3-dien-1-ylsulfanyl)-2H-chromen-2-one showed fluorescence properties. 1,1′,1″-[3,4-Dichlorobuta-1,3-diene-1,1,4-triyltris(sulfanediyl)]tris(2,4-dimethylbenzene) reacted with potassium tert-butoxide in petroleum ether to afford a mixture of isomeric 1,1′,1″-[4-chlorobuta-1,2,3-triene-1,1.4-triyltris(sulfanediyl)]tris(2,4-dimethylbenzene) and 1,1′,1″-[2-chlorobut-1-en-3-yne-1,1,4-triyltris(sulfanediyl)]-tris(2,4-dimethylbenzene). The GC/MS method was found to be useful for the separation of some sulfanyl-substituted butadiene isomer mixtures. The synthesized compounds were characterized by elemental analyses, mass spectrometry, UV-Vis, IR, and NMR (¹H, ¹³C) or fluorescence spectroscopy.     

Alcaloïdes steroidiques—CLXV : Action de l'eau et du methanol sur deux imino—carbinols cycliques steroidiques isomeres derives de la conanine

The hydrolysis in neutral conditions of the cyclic steroidal imino-carbinol 4, resulting from alkaline isomerisation of oxazirane 3, leads to the keto-aldehyde 6. The acid hydrolysis is preceded by isomerisation into the imino-carbinol 5 and the resulting keto-aldehyde is epimerized at carbon 17. The alkaline hydrolysis of the imino-carbinols 4 and 5 leads to the crotonized derivative 8. The imino-carbinol 4 gives a mixture of both carbon 18-epimers of the methoxylated imines 10 with methanol. These epimers can be equilibrated. The mixture of epimers leads by oxidation to two oxaziranes 12 and 13 which can be isolated.     

Thiocarbonyl ylides : Reactions and stereochemical properties of some 4-t-butylcyclohexyl derivatives

The azine from 4-t-butylcyclohexanone on treatment with hydrogen sulfide under pressure is converted to a mixture of stereoisomeric 1,3,4-thiadiazolidines. Dehydrogenation of this mixture with an alkyl azodicarboxylate afforded in quantitative yield (based on azine) a mixture of the three possible Δ³-1,3,4-thiadiazolines. These three isomers have been isolated and their structures have been established as trans,trans-3,11-di-[1,1-dimethylethyl]-14,15-diaza-7-thiadispiro[5.1.5.2]pentadeca-14-ene(5); the cis,cis-isomer (6), and the cis,trans-isomer (7). Pyrolysis of either 5 or 6 leads in quantitative yield to cis,trans-3,10-di-[1,1-dimethylethyl]thiadispiro[5.0.5.2]tridecane (8), the formation of which is rationalized by conrotatory ring closure of the same thiocarbonyl ylide (24) formed from either 5 or 6. Pyrolysis of 7 leads exclusively to a thiirane isomeric with 10 and which is assigned the cis,cis-structure (9). The thiiranes 8 and 9 are desulfurized by tri-n-butylphosphine to the anti- and syn-1-(1,1-dimethylethyl)-4-[4-(1,1-dimethylethyl)cyclohexylidene]cyclohexanes (11 and 12), respectively. The cycloadditions of the thiocarbonyl ylides derived from 5–7 with dimethyl acetylenedicarboxylate and dimethylazodicarboxylate have been examined but stereochemistries have not been assigned to these products. Cis additions to the olefins (11 and 12) have been investigated with the most attention having been paid to the reactions with osmium tetroxide. The configurations of the glycols expected from these reactions have been correlated by comparison with the three possible glycols (16–18) obtained from pinacol reduction of 4-t-butylcyclohexanone. These three glycols have been separated and their configurations assigned from PMR and IR data. A discussion of the stereochemical implications of the various results is given.     

Solvent Extraction Studies of Two Isomeric 5, 7, 7, 12, 12, 14-Hexamethy-1, 4, 8, 11-Tetraazacyclotetradecanes

The distribution ratios of two isomeric 5, 7, 7, 12, 12, 14-hexamethyl-1, 4, 8, 11-tetraazacyclotetradecane, tet c and tet d, in several solvent systems at 25.0°C as functions of hydrogen ion concentration were determined. The protonation constants and the distribution constants of these macrocyclic ligands and their protonated species were obtained from the variations of the distribution ratios in the range of 6<–log [H⁺]<14.     

Phyto – Monoterpene linalool as precursor to synthesis epoxides and hydroperoxides as anti carcinogenic agents via thermal and photo chemical oxidation reactions

Linalool (I) was extracted from Zingiber officinale. The oxidation of linalool using m-chloroperbenzoic acid at room temperature gave the mixture of 2,2,6-trimethyl-6-vinyl-tetrahydro-pyran-3-ol (IIa) & 2-(5-methyl-5-vinyl- tetrahydro-furan-2-yl)-propan-2-ol (IIa′), which cannot be separated. Whereas, the photo-epoxidation of it using hydrogen peroxide gave the above mixture IIa/IIa′, beside 2,2,8-trimethyl-6-oxianyl-tetrahydro-pyran-3-ol (IIb). It was evaluated for anti-oxidant, using erythrocyte hemolysis and ABTS methods. It showed inhibitory effect in case of erythrocyte hemolysis and low inhibitory effect in case of ABTS method. Photosensitization reactions of linalool with tetraphenyl porphyrin or chlorophyll produced a mixture of two isomeric hydroperoxides, 7-hydroperoxy-3,7-dimethylocta-1,5-dien-3-ol (IIIa) & 6-hydroperoxy-3,7-dimethyl octa-1,7-dien-3-ol (IIIb), which can be successfully separated. On the other hand, the cytotoxic activity of linalool (I) was tested against epdermoid carcinoma (HEP2), it has medium effect. Whereas, in case of human prostate cancer (PC-3), it has weak effect. From this study concludes that ginger has good antioxidant potential and this spice can be used to produce novel natural antioxidants and flavoring agent like linalool which recommends it as an active therapy for humans. Monoterpene linalool abstract singlet oxygen (¹O₂) by photosensitization reactions to produce these hydroperoxides, which are caused relatively little oxidative DNA damage.     

Cycloaddition reactions of 1,3-benzothiazines—I. : Reactions of 2-phenyl-4-H and 4-phenyl-2H-1,3-benzothiazine derivatives with substituted acetyl chlorides

6,7-Dimethoxy-2-phenyl-4$\text{H}$-1,3-benzothiazine (1) and 6,7-dimethoxy-4-phenyl-2$\text{H}$-1,3-benzothiazine (2) react with substituted acetyl chlorides to give linearly, and new angularly condensed β-lactam derivatives (4,5). Heating of the latter compounds with hydrogen chloride in anhydrous ethanol leads to the formation of the corresponding 4$\text{H}$- and 2$\text{H}$-1,3-benzothiazinium chloride, respectively. The configurations of these compounds (the mutual positions of the substituents relative to the β-lactam ring) were determined by ¹H and ¹³C studies, also making use of the aromatic solvent-induced shifts.     

Pyrroles and related compounds—XXXVI : Transformations of protoporphyrin-IX into harderoporphyrin,pemptoporphyrin, chlorocruoroporphyrin and their isomers

Treatment of protoporphyrin-IX dimethyl ester (8b) with 2 equiv of thallium(III) nitrate in methanol followed by chromatography affords good yields of a mixture of mono-acetal-mono-vinyl isomers (11b and 12b) which can be converted into the corresponding (2-hydroxyethyl)-vinyldeuteroporphyrins (13b and 14b) by hydrolysis and reduction with sodium borohydride. After separation by preparative TLC these compounds are transformed into isoharderoporphyrin trimethyl ester (3b) and harderoporphyrin trimethyl ester (2b) by treatment with CBr₄/Ph₃P (to afford the 2-bromoethyl derivatives), then sodium cyanide in 1-methylpyrrolidone (giving the 2-cyanoethyl compounds), followed by methanolysis. Formal syntheses of pemptoporphyrin dimethyl ester (4b) and its isomer (5b) are achieved by devinylation (resorcinol melt) of the haemins from the pure (2-hydroxyethyl)-vinyl isomers (14b and 13b) respectively, followed by demetallation.Controlled oxidation of protoporphydrin-IX dimethyl ester (8b) with osmium tetroxide gives starting material, mono-glycol-mono-vinyl isomers (23b and 24b), and bis-glycol (25b); this mixture can be separated by column chromatography. Further separation of the mono-glycols through preparative TLC followed by treatment with sodium periodate gives pure samples of chlorocruoroporphyrin dimethyl ester (6b) and its isomer (7b).In the TLC separations of unsymmetrically 2,4-substituted deuteroporphyrins studied, the 2-vinyl substituted isomers proved always to be the more polar (less mobile) componnets of the mixtures of isomers.     

Total syntheses of jaspamide (jasplakinolide) and geodiamolide A and B - 1. Stereoselective synthesis of (2S,4E,6R,8S)-8-hydroxy-2,4,6-trimethyl-4-nonenoicic acid1

The chiral aldehyde 7 was prepared by diastereoselective alkylation, subsequent 1,2- addition of isopropenylmagnesium bromide gave rise to a mixture (68:32) of the allylic alcohols 8 and 10 which was separated by recycling MPLC. Claisen rearrangement of the propionates of these alcohols under control of the enolate geometry finally yielded hydroxynonenoic acid 12b.     

A comparison of hydrogen bonding solvent effects on the singlet oxygen reactions of allyl and vinyl sulfides, sulfoxides, and sulfones

The singlet oxygen (¹Δ_g) photooxidations of 2-methyl-3-phenylthio-2-butene (1a), 1-[(4-nitrophenyl)thio]-2,3-dimethyl-2-butene (2c), 2-methyl-3-phenylsulfinyl-2-butene (3), 2-methyl-3-phenylsulfonyl-2-butene (6), and 1-[(4-nitrophenyl)sulfonyl]-2,3-dimethyl-2-butene (7c) were conducted in the following deuterated solvents: acetonitrile, benzene, chloroform, methanol, or methanol/water mixture. In each case the ene allylic hydroperoxide products and/or the [2+2] cycloaddition products were quantified and inspected for possible hydrogen bonding induced differences in product selectivity and regiochemistry. After comparison to literature values for related substrates, the results indicate that only photooxidations of vinyl sulfides are susceptible to hydrogen bonding solvent effects.     

Syntheses and structural characterization of some mono- and di-p-nitrophenyl[3]ferrocenophanes: X-ray structure of [3]ferrocenophane, 3-p-nitrophenyl[3]ferrocenophane, and 3,4′-bis-(p-nitrophenyl)[3]ferrocenophane; DFT calculations on ferrocene derivatives

[3]Ferrocenophane (3a) reacts in a Gomberg reaction with diazotized p-nitroaniline to give a mixture of mono- and di-substituted products. The isomeric pairs of 3- and 2-(p-nitrophenyl)[3]ferrocenophanes (4 and 5), as well as 3,4′- and 3,4-bis-(p-nitrophenyl)[3]ferrocenophanes (6 and 7) were separated from the mixture by column chromatography on Al₂O₃ and characterized by means of mass, IR, UV, ¹H-NMR spectroscopy, and by X-ray analysis (4 and 6). PM3/tm and density functional theoretical calculations on ferrocene (1) and ferrocenophane derivatives are reported. A refined X-ray structure determination of [3]ferrocenophane (3a) is given.     

The preparation of 3,5-disubstituted tetrahydro-4H-1,3,5-oxadiazine-4-thiones,tetrahydro-4H-1,3,5-thiadiazin-4-ones,and tetrahydro-4H-1,3,5-thiadiazine-4-thiones

The reaction of 1,3-disubstituted thioureas with formaldehyde under acidic conditions with removal of water yielded 3,5-disubstituted tetrahydro-4H-1,3,5-oxadiazine-4-thiones. When hydrogen sulfide was bubbled through the reaction mixture, the corresponding tetrahydro-4H-1,3,5-thiadiazine-4-thiones were formed. Similarly, starting from 1,3-disubstituted ureas, a number of tetrahydro-4H-1,3,5-thiadiazine-4-ones were prepared. The latter compounds were also oxidized to the corresponding sulfoxides and sulfones.     

Preparation of diastereomeric 5,8-methanobenzoxazino[2,1–6]- and [2,3–6]-1,3-benzoxazin-4-ones by reaction of norbornane/ene-condensed dihydro-1,3-oxazines with salicyl chloride

Norbornane and norbornene-condensed dihydro-1,3-oxazines 1–6 were converted with salicyl chloride to 5,8-methanobenzoxazino[2,1–6]- and -[2,3-b]-1,3-benzoxazin-4-ones 7–12. The addition takes place to the C ? N bond: after acylation, the intermediate is stabilized through cyclization to the aryl-substituted carbon by hydrogen chloride elimination. Diastereomers containing the oxazine rings in isomeric positions could be isolated in two cases. This is the first example of the isolation of diastereomers in such a salicyl chloride reaction. In contrast with earlier findings with reactions of related systems, no addition to the C ? C bond could be observed. The steric structures of the compounds were elucidated by ir, ¹H- and ¹³C-nmr spectroscopy.