Oxidation Of 1a Research Articles

Synthesis and In Vivo antitumor and antiviral activities of 2′‐deoxyribofuranosyl and arabinofuranosyl nucleosides of certain purine‐6‐sulfenamides, sulfinamides and sulfonamides

Abstract2′‐Deoxyribofuranosyl and arabinofuranosyl nucleosides of certain purine‐6‐sulfenamides, sulfinamides and sulfonamides have been prepared by sequential amination and controlled oxidation of the corresponding 6‐thiopurine nucleosides, and evaluated for antiviral and antitumor activities in mice. Amination of 2′‐deoxy‐6‐thioinosine (4a) and 9‐β‐D‐arabinofuranosyl‐6‐thiopurine (4c) with chloramine solution gave the corresponding 6‐sulfenamides 5a and 5c, respectively, which on selective oxidation with 3‐chloroperoxybenzoic acid (MCPBA) gave diastereomeric 9‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)purine‐6‐sulfinamide (6a) and 9‐β‐D‐arabinofuranosylpurine‐6‐sulfinamide (6c), respectively. However, oxidation of 5a and 5c with excess of MCPBA gave the corresponding 6‐sulfonamide derivatives 7a and 7c, respectively. Similar amination of 2′‐deoxy‐6‐thioguanosine (4b), ara‐6‐thioguanine (4d) and α‐2′‐deoxy‐6‐thioguanosine (8) gave the respective 6‐sulfenamide derivatives 5b, 5d and 9. Controlled oxidation of 5b, 5d and 9 gave (R,S)‐2‐amino‐9‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)purine‐6‐sulfinamide (6b), (R,S)‐2‐amino‐9‐β‐D‐arabinofuranosylpurine‐6‐sulfinamide (6d) and the α‐anomer of (6b) (10), respectively. The diastereomeric mixture of (R,S)‐10 was partially resolved and the structure of S‐10 was assigned by single‐crystal X‐ray diffraction analysis. Oxidation of 5b, 5d and 9 with excess of MCPBA afforded the respective 6‐sulfonamide derivatives 7b, 7d and 11. Nucleosides 5c and 7c were significantly active against Friend leukemia virus in mice, whereas 6c was somewhat less active. Of the 20 nucleosides evaluated, 12 exhibited biologically significant anti‐L1210 activity in mice. Nucleosides 6b and 7a at 173 mg/kg/day × 1 showed a T/C of 153, whereas 7d at 800 mg/kg/day × 1 showed a T/C of 153 against L1210 leukemia. The α‐nucleoside 9 at 480 mg/kg/day × 1 gave a T/C of 172. A single treatment with 6b, 7a, 7d and 9 reduced the body burdens of viable L1210 cells by more than 99.2%. The antileukemic activity of these novel nucleosides tended to parallel solubility.

Die Thermolyse oxidierter 1,3‐Dithiolane: Ein neuer Syntheseweg für Thiocarbonyl‐Verbindungen und Sulfine

Thermolysis of Oxidized 1.3‐Dithiolanes: A New Route for the Synthesis of Thiocarbonyl Compounds and SulfinesCF3,‐substituted 1,3‐dithiolanes 3a–c could be synthesized and subsequently oxidized to the 1,3‐dithiolane 1‐oxides 4b,c, 1,1‐dioxides 5a‐c and 1,1,3,3‐tetroxide 6b. The thioketones CF3(R)C=S (R = C6H5, 9a; CH3, 9b) and the trifluorothioacetaldehyde (9c) could be obtained in good yields by flash vacuum pyrolysis of 5a–c. By further oxidation of 5a–c the 1,3‐dithiolane 1,1,3‐trioxides were formed, and by their pyrolysis the sulfines CF3(R)C = SO (R = C6H5, 10a; CH3, 10b) were prepared. A unique rearrangement of 7b led to the 1,4‐dithiane 1,1,4‐trioxide 8b. Various Diels‐Alder adducts were synthesized for chemical proof of the existence of 9a–c and 10a, b, and stereochemical considerations are presented.

Metalation and Electrophilic Quenching of C-4 Functionalized Isoxazoles; VIII. Preparation of Derivatives of 5-Thioalkylisoxazoles

The lateral metalation and electrophilic quenching of isoxazoles bearing electron withdrawing groups in the 4-position 1 with disulfides, represents a selective, direct and synthetically useful entry to the thioalkyl derivatives . One exception to the formation of monothioalkyl major products was observed for the dianion of 4-[(2-hydroxymethyl-1-pyrrolidinyl)carbonyl]-3,5-dimethylisoxazole (1i) which was found to produce the 5-[bis(phenylthio)methyl]isoxazole derivative 3i as the major isolated product (66%). Oxidation of 2a with 3-chloroperoxybenzoic acid (MCPBA) proceeds selectively at sulfur in the presence of both isoxazole and oxazoline nitrogens to give the corresponding sulfoxide 4a (56%) or sulfone 5a (72%), respectively

Reactions with substituted acrylonitriles: A novel Synthesis of Polysubstituted Pyrimidines

Abstract3‐Arylacrylonitrile‐2‐thiocarboxamides (1a–d) reacted with S‐methylisothiourea to give 4‐amino‐6‐aryl‐2‐methylmercaptopyrimidine‐5‐carbonitriles (3a–d). The products 3a–d were also obtained via the reaction of 3‐arylacrylonitrile‐2‐carbonitriles (4a–d) with S‐methylisothiourea. Compounds 4a–d reacted with thiourea and urea to yield 4‐amino‐6‐aryl‐2‐mercaptopyrimidine‐5‐carbonitriles (5a–d) and 2‐hydroxy derivatives (5e–h) respectively. Oxidation of 5a–d with hydrogen peroxide afforded 5e–h. 5a–h were readily alkylated with methyl iodide to give 3a–d.

Synthesis and reactions of 4‐isopropylidene‐1‐aryl‐3‐methyl‐2‐pyrazolin‐5‐ones

AbstractThe reactions of 4‐isopropylidene‐1‐aryl‐3‐methyl‐2‐pyrazolin‐5‐ones 4a‐d were investigated under a variety of conditions. In the presence of thiols or piperidine, 4a‐d failed to yield conjugate addition products, presumably due to the steric bulk provided by the two methyl substituents of the isopropylidene side chain. Reaction of 4a‐d with hydrazine derivatives gave the 1‐aryl‐3‐methyl‐2‐pyrazolin‐5‐ones 3a‐d and isopropyl‐hydrazones. Treatment of 4a with potassium cyanide yielded a stable conjugate addition product which exists as a mixture of tautomers in different solvents. Also, oxidation of 4a with hydrogen peroxide gave a spiroepoxide 22, while m‐chloroperbenzoic acid oxidation afforded both the spiroepoxide 22, and a small quantity of a hydroxyspiroepoxide 23.

Die oxidative Spaltung von Pseudobasen 2-α-alkylierter 2,3-Cycloalkenopyridinium-Salze / Oxidative Cleavage of Pseudobases from 2-α-Alkylated 2,3-Cycloalkenopyridinium Salts

In contrast to former assumptions pyridinium salts with a tertiary 2-α-C-atom like 2 a and 16 are not oxidized to pyridinium-carbinol intermediates during alkaline hexacyanoferrate(III) oxidation because 10 yields the pyridones 11 and 12, both missing after oxidation of 2a. The title compounds 2 show the same reactivity against alkaline hexacyanoferrate(III). The pseudobases 14 suffer ring fission simultaneously forming the pyridones 6-8. 4 and 5 were characterized as further oxidation products of 2.

Synthesis, structure and reactivities of [6]paracyclophanes

The synthesis, structure and reactivities of [6]paracycophanes 2a-c, the smallest bridged [n]paracydophanes so far isolated, are described. The parent hydrocarbon 2a has been efficiently synthesized by oxidative decarboxylation of [6.2-2]propellenecarboxylic acid (7) by lead tetraacetate. The 8-carbomethoxy derivative 2b has been quantitatively synthesized by thermal valence isomerization of the [6.2.2]propelladiene (4b) (Dewar isomer of 2b). X-Ray structure analysis of the crystalline 2c has revealed that the benzene ring of 2c severely deformed into a boat conformation with deformation angles of α= 20.5° and β = 18.5°. Furthermore, the bond angles of the bridging chain (C(2), C(3), C(4) and C(5)) are considerably expanded from the normal sp3 angle. Vaporphase thermolysis of 2a gives the spiro triene 12 via homolysis at the benzyl position. Add-catalyzed isomerization of 2a with trifluoroacetic add takes place readily to afford the meta and ortho isomers 13a and 14a in a ratio of 1:3. UV irradiation of the ester 2b brings about valence isomerization to the Dewar isomer 4b which isomerizes slowly to the prismane derivative 15a on further irradiation. A [4+2] cycloaddition of 2a with N-phenyl-l,2,4-triazoline-3,5-dione occurs at room temperature to give mainly adduct 16. Addition of bromine to 2a takes place to furnish quantitatively the unstable 1,4-addition product 18. Oxidation of 2a with mCPBA readily takes place to give the dienone dimer 20 which affords on UV irradiation the cage diketone 21 derived from intramolecular photocycloaddition.

ChemInform Abstract: SYNTHESIS AND BIOLOGICAL ACTIVITY OF 5‐THIOBREDININ AND CERTAIN RELATED 5‐SUBSTITUTED IMIDAZOLE‐4‐CARBOXAMIDE RIBONUCLEOSIDES

AbstractDie aus (I) und (III) zugänglichen Verbindungen (II) und (IV) werden mit Ribavirin verglichen.

ChemInform Abstract: REACTIONS OF TRIMETHYLSILYL CYANIDE WITH TROPONE, 2‐PHENYLTROPONE, AND 2‐METHOXYTROPONE. FORMATIONS OF 2‐CYANO‐1‐HYDROXYTROPYLIDENE DERIVATIVES

AbstractDie Tropone (Ia) und (Ib) lassen sich über den Alkohol (IIIa) bzw. das Tautomerengemisch (IIIb)/ (IV) zu (V) Cyan‐substituieren.

Reactions of Trimethylsilyl Cyanide with Tropone, 2-Phenyltropone, and 2-Methoxytropone. Formations of 2-Cyano-1-hydroxytropylidene Derivatives

Abstract Reaction of trimethylsilyl cyanide (TMSCN) with tropone and 2-phenyltropone in the presence of a catalytic amount of zinc iodide in dichloromethane afforded silyl ethers of 7-cyano-1,3,5-cycloheptatriene-1-ol (2a) and 2-phenyl-7-cyano-1,3,5-cycloheptatriene-1-ol (2b), respectively. On the other hand, reaction of TMSCN with 2-methoxytropone gave 2-cyanotropone. Upon hydrolysis, 2a, and 2b yielded 2-cyano-1,3,5-cycloheptatrien-1-ol (3a) and a tautomeric mixture of 2-cyano-7-phenyl-1,3,5-cycloheptatrien-1-ol (3b) and 2-cyano-7-phenyl-3,5-cycloheptadien-1-one (4b). Oxidation of 3a and the tautomeric mixture of 3b and 4b with selenium dioxide in dioxane afforded 2-cyanotropone and 2-cyano-7-phenyltropone, respectively.

Polyesters derived from 1,4‐oxathian‐2‐ones

Abstract1,4‐Oxathian‐2‐one (1a) was prepared in high yield by oligomerization of methyl(2‐hydroxyethyl)mercaptoacetate (3) followed by catalytic depolymerization in vacuo. A similar sequence starting with methyl(2‐hydroxyethyl)sulfonylacetate (5) afforded the corresponding sulfone, 1,4‐oxathian‐2‐one‐4,4‐dioxide (1c), however, 1,4‐oxathian‐2‐one‐4‐oxide (1b) could not be obtained by this procedure. Ring opening melt polymerization of 1a and 1c afforded low molecular weight crystalline polyesters 2a and 2c. Oxidation of 2a with m‐chloroperoxybenzoic acid produced the corresponding polyester 2b containing sulfoxide groups. Thermogravimetric analyses and visual observations indicated 2b to be thermally unstable relative to 2a and 2c.

A novel sesquiterpene peroxide from Alpinia japonica (Thunb.) MIQ.

A novel sesquiterpene peroxide, hanalpinol (1a), has been isolated from the rhizomes of Alpinia japonica. Oxidation of 1a with pyridinium chlorochromate gave a crystalline, α, β-unsaturated ketone (2), whose structure was established by means of X-ray analysis. The IR spectrum of 1a revealed the presence of intramolecular hydrogen bonding, and acid treatment of 1a resulted in the formation of furopelargone B (4), which was present naturally in the same plant. This conversion reaction suggests that 4 is biosynthesized from 1a or its analog. Furopelargone A (3) was also isolated.

Preparation, Characterization and Reactivity of Diastereomeric Sulfoxides of 8,2′-S-Anhydroadenosine

Abstract The oxidation of 8,2′-S-anhydroadenosine (1a) has been investigated. The major product from the oxidation of 1a using 1-chlorobenzotriazole was the R-sulfoxide. The oxidation of 3′,5′-di-O-acetyl-8,2′-S-anhydroadenosine (1b) gave predominately the S-sulfoxide. These sulfoxides were found to be very succeptible to nucleophilic attack at C-8.

Nitroxides as reaction intermediates

Vinyl nitroxides 4 are obtained by oxidation of the nitrones 3, as was shown by esr studies and by identification of the reaction products. The formation of 4d–f is even observed in oxidation of the hydroxylamines 1d–f, nitroxides 2d–f and nitrones 3d–f being the intermediates. The high reactivity of the vinyl nitroxides 4 at their β-position is illustrated by the reactions of 4a with various compounds affording the nitroxides 7–10, respectively. Compound 4c reacts with its precursor 3c to give 11, 12, or 13, depending on the reaction conditions. From oxidation of 3a, c, and e the dimerization products 5a, c, and e, respectively, could be isolated. Whereas further oxidation of 5d yields 6d, the acyl nitroxides 14a and c are formed in the oxidation of 5a and c, respectively.The formation of quinone 23 in the reaction of 2-methyl-2-nitrosopropane with potassium tert-butoxide in isopropyl alcohol in the presence of oxygen is discussed. The nitroxide 20 has been detected in the reaction mixture. Imines 24 react with nitrosobenzene giving nitroxides 26. These are further oxidized by nitrosobenzene to afford nitrones 27. Whereas 27a and b could be isolated, 27c and d undergo further reaction yielding the diimines 30c and d along with dinitrone 29.The formation and reactions of imino nitroxides 31 and of the nitronyl nitroxide 41 are discussed. Electron spin resonance studies revealed the high reactivity of the imidazolyl-1,3-dioxides 46 and the imidazolyl-1-oxides 50, which easily form radicals 47–49 and 51, respectively, which are derived from secondary reactions.

Darstellung, Eigenschaften und Reaktivität von 2-, 3- und 4-Chloracyl(diphenyl)phosphanoxiden / Preparation, Properties and Reactivity of 2-, 3- and 4-Chloroacyl(diphenyl)phosphane Oxides

The highly reactive chloroacyl(diphenyl)phosphane oxides RC(O)-P(O)Ph2 (2a-d, g) [R = HCCl2 (a), CCl3 (b), CH3CHCl (c), CH3CCl2 (d), ClCH2CH2 (e), CH3CHClCH2 (f), ClCH2(CH2)2 (g)] are obtained by oxidation of the thermally labile chloroacyl(diphenyl)- phosphanes RC(O)-PPh2 (1a-d, g) with molecular oxygen in ether at low temperatures. While hydrolysis leads to a complete decomposition of 2a-d, g, the oxidation of 1a, c, e-g with oxygen in the presence of HP(O)Ph2 yields the diphosphorylated alcohols RC[P(O)Ph2]2OH (3a, c, e-g). 3e, f can be interpreted as trapping products of the not isolable oxides 2e, f. In tetrachloroethene a partial transformation of 3a into the phosphinate RC[P(O)Ph2][OP(O)Ph2]H can be observed which can be followed 31P{1H}-NMR spectroscopically. In solution the alcohols 3c, e-g decompose to give HP(O)Ph2 and the corresponding phosphane oxides 2c, e-g.

Synthesis of 4,5-disubstituted imidazoles

Introduction of a triphenylmethyl group on the nitrogen of imidazole-4,5-dicarboxylic acid esters or 4,5-dihydroxymethylimidazole resulted in deactivation of the functional group adjacent to the protecting group and allowed reactions to take place preferably or exclusively on the other functional group. Thus, dimethyl 1-triphenylmethylimidazole-4,5-dicarboxylate (2), on treatment with hydrazine and methylamine produced methyl 4-hydrazinocarbonyl-1-triphenylmethylimidazole-5-carboxylate (3a) and methyl 4-methylaminocarbonyl-1-triphenylmethylimidazole-5-carboxylate (3b), respectively. Reduction of 2 with lithium borohydride gave methyl 4-hydroxymethyl-1-triphenylmethylimidazole-5-carboxylate (4a). Treatment of 4,5-dihydroxymethyl-1-triphenylmethylimidazole (5a), with trimethylacetyl chloride and with acetic anhydride afforded 5-hydroxymethyl-4-trimethylacetoxymethyl-1-triphenylmethylimidazole (6a), and 4-acetoxymethyl-5-hydroxymethyl-1-triphenylmethylimidazole (6c), respectively. Oxidation of 5a with activated manganese dioxide produced the monoaldehydes 9 and 10 in a ratio of 11:1. A new mild process for deprotection of N-triphenylmethylimidazoles, compatible with acid sensitive groups in the molecule, is reported. The synthesis of several 4,5-disubstituted imidazoles is also described.

Reaction of 3‐methoxy‐17‐methylmorphinan‐6‐one with formaldehyde

AbstractReaction of 3‐methoxy‐17‐methylmorphinan‐6‐one (1) and formaldehyde with the presence of calcium hydroxide in aqueous dioxane gave 7,7‐bis(hydroxymethyl)‐3‐methoxy‐17‐methyl‐5‐methylenemorphinan‐6β‐ol (2a). Catalytic reduction of 2a yielded the 5α‐methyl compound, 2b. Tosylation of 2a,b followed by lithium triethylborohydride reduction gave either 7α‐methyl‐6β,7β‐oxetanes 4a,b or 7,7‐dimethyl‐6β‐ols 5a,b, depending on reaction conditions. The C‐6 ketones 6a,b were prepared by oxidation of 5a,b. One compound in this series, 6a, had antinociceptive activity.

Chemie der Amino‐oxime, XIV. Synthese und Reaktionen von 2‐[α‐(E)‐(Hydroxyimino)benzyl]‐3‐imidazolin‐3‐oxiden

The Chemistry of Amino Oximes, XIV Synthesis and Reaction of 2‐[α‐(E)‐(Hydroxyimino)benzyl]‐3‐imidazoline 3‐Oxides2‐Benzoyl‐4‐phenyl‐1‐(p‐tolyl)‐3‐imidazolin 3‐oxide (3b) has been prepared by cyclocondensation of α‐(p‐toluidino)acetophenone oxime (1a) with phenylglyoxal and transferred into 2‐[α‐(E)‐(hydroxyimino)benzyl]‐4‐phenyl‐1‐(p‐tolyl)‐3‐imidazoliune 3‐oxide (5a). 5a is identical with the product prepared by oxidation of 1a, with FeCl3.

A total synthesis of 4-cyano-1,3-dimethoxy-2-azaestra-1,3,5(10)-trien-17β-ol and its configuration assignment

A total synthesis of 4-cyano-1,3-dimethoxy-2-azaestra-1,3,5(10)-trien-17β-ol(6a) has been achieved starting from 4-cyano-1,3-dimethoxy-5,6,7,8-tetrahydroisoquinoline(1a). Dichromate oxidation of1a gave the 8-oxo derivative(1c) whose structure was confirmed unambiguously by the lanthanide induced chemical shift method. Grignard reaction of1c with vinyl magnesium bromide followed by condensation of the vinyl-alcohol with 2-methyl-cyclopentane-1,3-dione resulted in the seco-dione(2) in 50% yield, which was cyclised withp-toluene sulfonic acid to the pentaenone(3a). Sodium borohydride reduction of3a, stereoselective partial hydrogenation of the 14,15-double bond in3b followed by isomerisation of the 8,9-double bond in4 to 9,11-position and catalytic reduction of the 9,11-double bond gave the title compound(6a). The 14α, 8β, 9α-configuration in6 was tentatively assigned on the basis of its NMR spectrum. The CMR spectra of the steroidal derivative and also the tetrahydroisoquinoline derivative(1b) have been studied and the configuration assigned to the steroid has also been supported by this study.

Synthese und Stabilisierung von (Benzoyl-und Pentafluorbenzoyloxy)diphenylphosphan und Vergleich mit den entsprechenden isomeren Aroyldiphenylphosphanoxiden / Synthesis and Stabilization of (Benzoyl-and Pentafluorobenzoyloxy)diphenylphosphane and Comparison with the Corresponding Isomeric Aroyldiphenylphosphane Oxides

Abstract (Benzoyloxy)-and (pentafluorobenzoyloxy)diphenylphosphanes RC(O)OPPh2 (2a, b) [R = C6H5 (a), C6F5 (b)] can be obtained by reaction of ClPPh2 (1) with NaO2CC6H5 and AgO2CCeF5, respectively [eq. (1)]. Oxidation of 2a with molecular oxygen yields (benzoyl-oxy)diphenylphosphane oxide (3a) [eq. (2)]. The complexes (OC)5CrPPh2OC(O)R (5a, b) are formed by the action of Na2OCC6H5 and AgO2CC6F5, respectively on (OC)5CrPPh2Cl (4) [eq. (3)]. The chemical and spectroscopical properties of the (aroyloxy)diphenylphosphanes (2 a, b) are compared with the corresponding aryldiphenylphosphane oxides.