Synthesis and olfactory properties of (−)-(1R,2S)-Georgywood

The enantiomers of Georgywood^® were synthesized from (E)-2-methyl-6-methylene-nona-2,7-diene and methacrylaldehyde followed by oxidation of the Diels–Alder adduct and classical racemate separation of the acid with optically-active N-methylephedrine. Conversion to the final ketone and olfactory evaluation showed that the (−)-(1R,2S)-enantiomer is more powerful by a factor of >100 than its antipode. The absolute configuration was determined by conformational studies and CD-analysis.     

(R)-Oxynitrilase catalyzed synthesis of (R)-ketone cyanohydrins

(R)-Oxynitrilase from almonds (Prunus amygdalus) catalyzes the enantioselective addition of HCN to ethyl alkyl ketones 1 in diisopropyl ether yielding (R)-ethyl alkyl ketone cyanohydrins (R)-2, which are hydrolyzed under acid catalysis to give the -hydroxy acids (R)-3. This (R)-oxynitrilase also catalyzes the enantioselective addition in aqueous citrate buffer (50 mM, pH 4.0), as demonstrated for the preparation of (R)-methyl alkyl ketone cyanohydrins (R)-5 which are obtained in high enantiomeric excesses comparable to those in diisopropyl ether as solvent.     

Analogues of DIOP. Synthesis, reactivity, and NMR behaviour

The (4R,5R)-4,5-Bis(diphenylphosphinomethyl)-2-(-naphthoxy)-1,3,2-dioxaphospholane (1) and (4R,5R)-4,5-bis(diphenylphosphinomethyl)-2-dimethylamino-2-oxo-1,3,2-dioxaphospholane (2), analogues of the chiral bisphosphine ligand DIOP, have been synthesized. Both compounds have a second phosphorus functionality in the backbone of the chiral bisphosphine. That the reactivities of the various phosphorus atoms in 1 are different was shown for the reaction with BH₃. The complexation behaviour of 1 towards Rh^I was studied with the aid of ³¹P NMR spectroscope.     

Synthesis of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-imidazo[4,5-b]pyridin-2-amine. An aza analogue of enviroxime

6-[[(Hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-imidazo[4,5-b]pyridin-2-amine ( 1 ), an aza analogue of enviroxime, was synthesized in eight steps from 6-hydroxynicotinic acid ( 2 ). Acid 2 was nitrated, chlorinated with phosphorus pentachloride, and subjected to Friedel-Crafts aroylation to give 6-chloro-5-nitro-3-pyridyl phenyl ketone ( 5 ). Amination of 5 was followed by reduction of the nitro group and condensation with ethoxycarbonylisothiocyanate to give 6-benzyl-2-ethoxycarbonylamino-1H-imidazo[4,5-d]pyridine ( 8 ). The ethoxycarbonyl moiety of 8 was cleaved, N-1 was isopropylsulfonylated, and the carbonyl moiety was condensed with hydroxylamine to give 1 . Compound 1 was inactive against rhinovirus 1B and poliovirus type 1 .     

Synthesis of (+)-carpamic acid from (+)-alanine

(+)-Carpamic acid [(2′R,5′S,6′S)-8-(5′-hydroxy-6′-methylpiperidin-2′-yl)octanoic acid, 1] was synthesized from (S)-alanine, employing intramolecular and reductive amination of acyclic amino ketone 8 as the key step to generate the piperidine ring.     

Resolution of 1-substituted-3-methyl-3-phospholene 1-oxides by molecular complex formation with TADDOL derivatives

The antipodes of 1-aryl-, 1-alkyl- and 1-alkoxy-3-methyl-3-phospholene 1-oxides 1a–h and 1-phenyl-3-methyl-3-phospholene 1-sulfide 1i were separated in good yields and high enantiomeric excesses (up to >99% ee) by resolution via formation of diastereomeric complexes with either (−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane 2 (TADDOL) or (−)-(2R,3R)-,,′,′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol 3. The stereostructure of the supramolecular formations and the absolute configurations of the 3-phospholene oxides 1a, 1e and 1f were elucidated by single crystal X-ray crystallography. CD spectroscopy was also useful in determining the absolute configurations of some phospholene oxides 1b, 1c, 1g and 1h.     

Synthesis of alkyl (4,5-Dichloroisothiazol-3-yl) ketones and some of their derivatives

Reactions of 4,5-dichloroisothiazol-3-ylcarbonitrile with methylmagnesium iodide and ethylmagnesium bromide afforded the corresponding alkyl (4,5-dichloroisothiazol-3-yl) ketones. The reaction of (4,5-dichloroisothiazol-3-yl) methyl ketone with morpholine and piperidine provided 5-morpholino-(piperidino)-substituted derivatives, by the action of sodium borohydride in 2-propanol the keto group was reduced to alcoholic hydroxy group. The bromination of (4,5-dichloroisothiazol-3-yl) methyl ketone with elemental bromine gave bromomethyl (4,5-dichloroisothiazol-3-yl) ketone, whose reaction with thiourea resulted in 2-amino-4-(4,5-dichloroisothiazol-3-yl)thiazole.     

Direct asymmetric aldol reaction catalyzed by simple prolinamide phenols

Simple prolinamides 1a–f were synthesized, and their catalytic effects on the direct asymmetric aldol reactions in organic solvents and in water were evaluated. Prolinamide phenols 1a–d were found to be effective catalysts for the reaction of aromatic aldehydes with cyclohexanone in neat ketone and in water. The anti-aldol products were obtained with up to 98/2 anti/syn ratio and 96% ee in neat ketone, 98/2 anti/syn ratio and 99% ee in water, respectively.     

Synthesis and catalytic activity of new chiral unsymmetrical Mn(III)-Schiff-base complexes containing salicylaldehyde and 1-(2-hydroxyphenyl)ketone units

Two new chiral unsymmetrical (non-C₂-symmetric) Schiff-base ligands containing salicylaldehyde and 1-(2-hydroxyphenyl)ketone units were synthesized from (R,R)-1,2-diphenylethylenediamine as the chiral diamine using a stepwise approach. The Mn(III) complexes of the ligands were subsequently used as catalysts in asymmetric epoxidation of unfunctionalized alkenes and the results were compared with those obtained using typical C₂-symmetric Mn(III)–salen complexes. Possible reasons for the differences in reactivity and selectivity between the two types of catalysts are briefly discussed.     

The enthalpies of formation of two dibenzocyclooctadienones

The standard molar enthalpies of formation (Δ_fH_m⁰(s)/kJmol⁻¹) for 2,3:6,7-dibenzocycloocta-2,6-dien-1-one and 2,3:7,8-dibenzocycloocta-2,7-dien-1-one [6H-11,12-dihydro-dibenzo[a,e]cycloocten-5-one (ketone 1) and 10H-11,12-dihydrodibenzo[a,d]-cycloocten-5-one (ketone 2), respectively] were derived from enthalpies of combustion, measured by means of a microbomb calorimeter. The fusion and vaporization enthalpies of these compounds were obtained from DSC and correlation gas chromatography measurements. The standard molar enthalpies of formation in the gas phase were calculated by combining the condensed phase standard molar enthalpies of formation with the fusion and vaporization enthalpies adjusted to 298.15 K. Values for Δ_fH_m⁰(g) of (−39.9±5.5) and (−14.8±5.3) kJ mol⁻¹ were obtained for 2,3:6,7-dibenzocycloocta-2,6-dien-1-one and 2,3:7,8-dibenzocycloocta-2,7-dien-1-one, respectively. Quantum chemical calculations are reported for the compounds investigated experimentally and an additional four isomers. Isomerization enthalpies are derived from computed energies. The enthalpies of formation are also calculated by group additivity, compared with the experimental values and then correlated with the structure of the molecules investigated. The X-ray analysis of ketone 1 is also reported.     

Synthesis and Characterization of Soluble Reactive Copoly (aryl ether ketone ketone)

Poly (aryl ether ketone)s are a category of high performance engineering plastics, widely used in electronic, electric, and military industries1. For their general excellent properties, many new products are developed. In recent years, much attention has been paid to synthesize soluble or reactive poly (aryl ether ketone)2,3. In this letter, we report the synthesis of a novel soluble reactive copoly (aryl ether ketone ketone) from 2,2-p-hydroxyphenyl-iso-propane 3, functionalized chemical 1, a…     

Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones

Towards the synthesis of sterically hindered optically active secondary alcohol 2, yeast strains (Candida floricola IAM 13115 and Trichosporon cutaneum IAM 12206) with si-face hydride attack on isopropyl phenylsulfonylmethyl ketone 1 were developed by screening. Strains with complementary re-facial selectivity (Pichia angusta IAM 12895 and Pichia minuta IAM 12215) were also found. Based on the substrate specificity studies of these four strains, microbial reduction was applied to the synthesis of (3S,5S)-2,6-dimethyl-3,5-heptanediol 12a.     

Haloacetylated enol ethers. 6 [5]. Synthesis of 4,5-trimethylene-4,5-dihydroisoxazoles

The investigation of the effect of the cyclopentane ring on the regiochemistry of the reactions of 2-acetylcyclopentanones 1a-d and β-methoxyvinyl trifluoromethyl ketone derivative 2a with hydroxylamine hydrochloride is reported. The reactions give regiospecifically the 4,5-trimethylene-4,5-dihydroisoxazoles 3a-d in good yields.     

Ab initio study of the tautomeric forms of some quinolinediones

7,8-dihydroquinoline-4,5 (1H,6H)-dione (1) and 7,8-dihydroquinoline-2,5-(1H,6H)-dione (2) in their tautomeric oxo and hydroxy forms have been studied by ab initio Hartree-Fock calculations; tautomerization energies predict a more stable hydroxy structure having an intramolecular hydrogen bond for compound 1, whereas the oxo form is slightly-preferred for compound 2. Fourier Transform-Infra Red (FT-IR) spectra in CHCl₃ solution indicate that the predicted most stable tautomers in the vapour phase remain as such.     

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide 1 and its silver salt 10 with different alkylating agents (diazomethane, diazoacetone, bromoacetone, α-bromoacetophenone, methyl iodide, methyl vinyl ketone) was studied. Alkylation of compound 1 with diazo compounds and salt 10 with halocompounds results predominantly in O-alkylation products, 1-alkoxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxides. The Michael reaction of compound 1 with methyl vinyl ketone involves the triazole nitrogen atom to give 1-(3-oxobutyl)-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 3,4,6-trioxide. The structures of the compounds synthesized were established by ¹H, ¹³C, ¹⁴N NMR spectroscopy and mass spectrometry.     

Efficient Synthesis of 4,5‐Disubstituted‐3‐Toluenesulfonyl Glutarimides. Application to the Formal Synthesis of Mappicine Ketone

Various 4,5‐disubstituted‐3‐sulfonyl glutarimides 3 were synthesized from α‐sulfonyl acetamide 1 and ethyl α,β‐disubstituted acrylate esters 2 via stepwise facile [3+3] annulation in moderate yield. The synthesis of pyridin‐2‐one 9 , a key intermediate for mappicine ketone ( 4 ) synthesis, was also reported.     

Synthesis, characterization and catalytic activity in Heck-type reactions of orthometallated Pd and Pt complexes derived from (1R,2R)-1,2-diaminocyclohexane

The chiral bis-imine (1R,2R)-C₆H₁₀-[E---N=CH---C₆H₃---3,4-(OMe)₂]₂ 1 (LH) reacts with [Pd(OAc)₂] (1:1 molar ratio; OAc=acetate) giving the orthometallated [Pd(OAc)(C₆H₂---4,5-(OMe)₂---2-CH=N-(1R,2R)-C₆H₁₀---N=CH---C₆H₃-3′,4′-(OMe)₂-κ-C,N,N)] 2 (abbreviated as [Pd(OAc)(L-κ-C,N,N)]), through C---H bond activation on only one of the aryl rings and N,N-coordination of the two iminic N atoms. 2 reacts with an excess of LiCl to give [Pd(Cl)(L-κ-C,N,N)] 3. The reaction of 3 with AgClO₄ and neutral or anionic ligands L′ (1:1:1 molar ratio) affords [Pd(L-κ-C,N,N)(L′)](ClO₄) (L′=PPh₃ 4a, NCMe 5, pyridine 6, p-nitroaniline 7) or [Pd(I)(L-κ-C,N,N)] 8. Complex 4a reacts with wet CDCl₃ giving [Pd(C₆H₂---4,5-(OMe)₂---2-CH=N-(1R,2R)---C₆H₁₀---NH₂-κ-C,N,N)(PPh₃)](ClO₄) 4b as a result of the hydrolysis of the C=N bond not involved in the orthometallated ring. The molecular structure of 4b·CH₂Cl₂ has been determined by X-ray diffraction methods. Cleavage of the Pd---N bond trans to the C_aryl atom can be accomplished by coordination of strongly chelating ligands, such as acetylacetonate (acac) or bis(diphenylphosphino)ethane (dppe), forming [Pd(acac-O,O′)(L-κ-C,N)] 9 and [Pd(L-κ-C,N)(dppe-P,P′)](ClO₄) 12, while classical N,N′-chelating ligands such as 1,10-phenantroline (phen) or 2,2′-bipyridyl (bipy) behave as monodentate N-donor ligands yielding [Pd(L-κ-C,N,N)(κ¹-N-phen)](ClO₄) 10 and [Pd(L-κ-C,N,N)(κ¹-N-bipy)](ClO₄) 11. Treatment of 1 with PtCl₂(DMSO)₂ (1:1 molar ratio) in refluxing 2-methoxyethanol gives Cl₂Pt[(NH₂)₂C₆H₁₀---N,N′] 13a and [Pt(Cl)(C₆H₂---4,5-(OMe)₂---2-CH=N-(1R,2R)---C₆H₁₀---NH₂-κ-C,N,N)] 13b, while [Pt(Cl)(L-κ-C,N,N)] 14 can be obtained by reaction of [Pt(μ-Cl)(η³-2-Me---C₃H₄)]₂ with 1 in refluxing CHCl₃. Complexes 2 and 3 catalyzed the arylation of methyl acrylate giving good yields of the corresponding methyl cinnamates and TON up to 847 000. Complex 3 also catalyzes the hydroarylation of 2-norbornene, but with lower yields and without enantioselectivity.     

Studies on the extraction and determination of metals-I Extraction of hafnium into methyl isobutyl ketone and tributyl phosphate

The effect of various factors on the distribution of hafnium ( 5.60 × 10⁻⁴M) between different acids and methyl isobutyl ketone (MIBK) or tributyl phosphate (TBP) was studied by using ^{176 + 181} Hf as a tracer, when the extraction is made from 7.5–11M hydrochloric acid with an equal volume of IM TBP in benzene, hafnium is extracted quantitatively (>99%). The hafnium can be stripped with 1–3M hydrochloric acid.     

An unexpected [2+2]-cycloaddition reaction of 4-methyldithieno-[3,4-b:3′,2′-d]pyridinium iodide with dimethyl acetylenedicarboxylate

An unexpected [2+2]-cycloaddition occured in the reaction of 4-methyldithieno-[3,4-6:3′,2′-d]pyridinium iodide (3)with two equivalents of DMAD, giving 4-(trans-1,2-dicarbomethoxy-2- iodovinyl)-5-methyl-6,7-dicarbomethoxy-4,5-dihydrothieno [23-c]quinoline (4) in 54% yield. 4 is formed via 4-methyl-5-(trans-1,2-dicarbomethoxy-2-iodo-4,5-dihydrothieno [3,4-b:3′,2′-d]pyridine (16), followed by [2+2]-cycloaddition. The primary adduct rearranges via a thiepin to an episulfide which eliminates sulfur to give 4.     

Synthesis of 6,7-dihydrobenzo[4,5]cyclohept-[1,2-b]indol-12(5H)-one and related compounds

The synthetic routes of 6,7-dihydrobenzo[4,5]cyclohept[1,2-b]indol-12(5H)-one 5 from either 1-methyl or 1-sulfonylindole-2-carboxaldehyde 1 or ethyl 1,2-dimethylindole-3-carboxylate 6 are reported. The structure of the ketone 5a was confirmed by X-ray crystallography. Several indole derivatives have been prepared with potential antitumor activity.