Chromium Trioxide-pyridine Research Articles

Synthesis of phosphonomethylated acid chlorides, alcohols, and aldehydes of the furan series

Diethoxyphosphorylmethyl derivatives of furancarboxylic acids react with thionyl chloride in the presence of DMF to form the corresponding acid chlorides. Compounds synthesized were reduced with sodium borohydride in the DMF-dioxane medium to give hydroxymethyl compounds. Obtained phosphorylated alcohols were oxidized to aldehydes by chromium trioxide-pyridine complex in methylene chloride. The diethoxyphosphorylmethyl group remains untouched in all these transformations. A series of phosphorylated acid chlorides, alcohols, and aldehydes including all six versions of mutual location of phosphorus-containing substituent and another functional group in the furan ring was synthesized. It is established that 2,3- and 3,2-(diethoxyphosphorylmethyl)(chlorocarbonyl)furans in the course of vacuum distillation undergo cyclization to 4,5(2,3-furo)- and 4,5(3,2-furo)-1,2-oxaphosphorines.

Synthesis of 4‐, 5‐, 6‐ and 7‐Nitroindole‐2‐methanols and 4‐, 5‐, 6‐ and 7‐Nitroindole‐2‐carbaldehydes.

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Synthesis of 4-, 5-, 6- and 7-nitroindole-2-methanols and 4-, 5-, 6- and 7-nitroindole-2-carbaldehydes

The synthesis of 4-, 5-, 6- and 7-nitroindole-2-methanols and the corresponding 2-aldehydes is described. The nitroindole-2-methanols were prepared by the reduction of ethyl 4-, 5-, 6- and 7-nitroindole-2-carboxylates with sodium borohydride in methanol/tetrahydrofuran. 4-, 5-, 6- and 7-Nitroindole-2-aldehydes were prepared from the nitroindole-2-methanols using PCC (pyridinium chlorochromate) and with chromium trioxide–pyridine prepared in situ.

Antimitotic agents. Alterations at the 2,3-positions of ethyl (5-amino-1,2-dihydropyrido[3,4-b]pyrazin-7-yl)carbamates

The reaction of ethyl (6-amino-4-chloro-5-nitropyridin-2-yl)carbamate (2) with alpha-amino ketone oximes gave 4-[(2-oxoethyl)amino]pyridine oximes 3, which were reductively cyclized to give a series of ethyl (1,2-dihydro-pyrido[3,4-b]pyrazin-7-yl)carbamates (6). In another approach, alpha-nitro ketones, alpha-oximino ketones, and alpha-nitro alcohols were reduced to give alpha-amino alcohols, which were reacted with 2 to give 4-[(2-hydroxyethyl)amino]pyridines (5). Oxidation of these alcohols with the chromium trioxide-pyridine reagent gave the corresponding ketones (4), which were also reductively cyclized to give 6. Structure-activity relationship studies indicated that alterations at the 2- and 3-positions of the pyrazine ring of 6 had a significant effect on cytotoxicity and the inhibition of mitosis in cultured lymphoid leukemia L1210 cells. Compounds that exhibited in vitro cytotoxicities at less than 1 nM showed the same level of in vivo activity, whereas the less potent compounds showed wide variations in their in vivo activity.

Syntheses of disaccharides with (1→4)-β glycosidic linkages related to the 4- and 6-sulfates and the 4,6-disulfates of chondroitin

The sodium salts of the 6′-sulfate 12, the 4′-sulfate 15 and the 4′,6′-disulfate 17 of benzyl 4- O-(β- d-galactopyranosyl)-β- d-glucopyranosiduronate 10 have been synthesized. Methyl [benzyl 2,3-di- O-benzoyl-4- O-(2,3-di- O-benzoyl-β- d-galactopyranosyl)-β- d-glucopyranosid]uronate ( 9) has been prepared as a key intermediate from benzyl 4′,6′- O-benzylidene-β- d-lactopyranoside ( 2). Protection of 2 at C-6 with the tert-butyldimethylsilyl group, followed by O-perbenzoylation and disilylation, gave benzyl 2,3-di- O-benzoyl-4- O-(2,3-di- O-benzoyl-4,6- O-benzylideneβ- d-galactopyranosyl)-β- d-glucopyranoside ( 7). Oxidation of the 6-position of 7 protocol to be difficult. However, 7 could be converted into the tert-butyl glucuronate 8 using chromium trioxide-pyridine and tert-butanol. Simultaneous hydrolysis of the benzylidene acetal and the tert-butyl ester groups, followed by esterification of the resulting free acid with diazomethane, yielded 9. Compound 9 was directly sulfated with sulfur trioxide-trimethylamine within 12 h to give the 6′-sulfate 11. The 4′,6′-disulfate 16 was accessible by running the reaction under the same conditions for 14 days. The 4′-sulfate 14 was obtained after protecting the 6′-OH group of 9 with benzoyl cyanide to give the 6′-benzoate 13 followed by sulfation under more vigorous reaction conditions. Deesterification of 9, 11, 14, and 16 was achieved by treatment with aqueous sodium hydroxide in tetrahydrofuran to give 10, 12, 15, and 17, respectively.

A Synthesis of Furans from Epoxycarbonyl Precursors

Abstract Following our study of the preparation of 2-ethyl-4-methylfuran (2a) by rearrangement of 5-methyl-5,6-epoxy-3-hexanone (1a),1 we undertook an investigation of the conversion of other epoxycarbonyl precursors to furans in order to determine the scope and utility of this transformation. The transformations examined in the present study are shown below. The epoxycarbonyl substrates were conveniently prepared from commercially available unsaturated alcohols by first expoxidation with m-chloroperoxybenzoic acid followed by oxidation with chromium trioxide-pyridine reagent in methylene chloride solution.2

Cyclization and rearrangement of diterpenoids. IV. Synthesis of Δ12- and Δ13(14)-iso-20-deoxyluteones

Δ12- and Δ13(14)-Iso-20-deoxyluteones have been synthesized from 13E- and 13Z-bicyclogeranylgeranylacetones. The latter were reduced to the corresponding alcohols, which were acetylated, and the acetates obtained were cyclized with fluorosulfonic acid in nitropropane. The reaction product was saponified to a mixture of tricyclic alcohols which were oxidized with the chromium trioxidepyridine complex to a mixture of Δ12- and Δ13(14)-iso-20-deoxyluteones and this was separated chromatographically.

Synthesis of some steroid spin labels

An improved synthesis of spin-labeled cortisol, cortisone, and testosterone using N, N'-cyclohexylcarbodiimide (DCC) is reported. The spin labeled steroids are shown to result from the esterification at the most reactive C(21) and C(17) hydroxyl groups. A mild and high yield oxidation of cortisol spin label to cortisone spin label by chromium trioxide-pyridine is also discussed.

Peracid oxidation of methyl esters of γ-hydroxy-α,β-unsaturated fatty acids

Oxidation of methyl 4-hydroxy- trans-2-octadecenoate (I) with m-chloroperbenzoic acid gave a rearrangement product characterized as methyl 3-keto-4-hydroxyoctadecanoate (II). Chromium trioxide-pyridine oxidation and sodium borohydride reduction of (II) yielded methyl 3,4-diketooctadecanoate (III) and 1,3,4-octadecane-triol (IV), respectively. The structures of these fatty acid derivatives are determined by chemical methods, elemental analysis, infrared (IR) and proton nuclear magnetic resonance spectroscopy (NMR) as well as by gas chromatography/mass spectrometry (GC-MS). The intramolecular isomerization of epoxy to keto group provides a useful method for the preparation of long-chain β,γ-ketol acids.

The Total Synthesis of (+)-Taxoquinone, (−)-7α-Acetoxyroyleanone, (−)-Dehydroroyleanone, (−)-Horminone, (−)-7-Oxoroyleanone, and (+)-Inuroyleanol

Abstract Methylation of 12-benzoyloxyabieta-8,11,13-trien-11-ol with methyl iodide afforded 11-benzoyloxy-12-methoxyabieta- and 12-benzoyloxy-11-methoxyabieta-8,11,13-triene (9). Oxidation of the latter product with chromium trioxide, followed by sodium borohydride reduction and acetylation, gave 7β-acetoxy-12-benzoyloxy-11-methoxyabieta-8,11,13-triene (17) and its 7α-acetoxy isomer (18) in a ratio of ca. 5 : 1. On the other hand, treatment of 9 with lead tetraacetate produced 17 and 18 in a ratio oi ca. 1 : 2. The 7β-acetate (17) was then oxidized with chromium trioxide and the resulting p-quinone derivative was hydrolyzed with aqueous sodium hydroxide to give taxoquinone (1), which on dehydration gave dehydroroyleanone. Similarly, the 7α-acetate (18) was converted into horminone (4) via the p-quinone derivative, which was treated with aqueous sodium hydrogencarbonate to give 7α-acetoxyroyleanone. Oxidation of 4 with manganese dioxide afforded 7-oxoroyleanone. Methylation of 1 with diazomethane, followed by oxidation with a chromium trioxide-pyridine complex, afforded 12-methoxyabieta-8,12-diene-7,11,14-trione, which on reduction with sodium dithionite gave inuroyleanol.

Synthesis of epimeric 2-d1-5.BETA.-pregnane-3,11,20-triones.

In order to clarify the stereochemistry of hydrogen loss from the C-2 position during microbial transformation of 5β-pregnane-3, 11, 20-trione into the Δ1-unsaturated compound, the stereospecific synthesis of epimeric C-2 deuterated substrates has been carried out. A key intermediate, 5β-pregn-2-ene-11α, 20β-diol diacetate, was obtained from the readily available 11α-hydroxyprogesterone through two synthetic routes. The trans-diaxial opening of the 2β, 3β-epoxide with lithium aluminum deuteride provided the 2α-d1-3β-ol. Deuterioboration of the Δ2-olefin and subsequent oxidation of the organoborane afforded the 2α-d1-3β-ol. On oxidation with chromium trioxide-pyridine complex, the epimeric 2-d1-5β-pregnane-3β, 11α, 20β-triols were converted to the desired 2-d1-5β-pregnane-3, 11, 20-triones.

ChemInform Abstract: PREPARATION OF D‐B‐FRIEDOOLEAN‐5(10)‐EN‐1‐ONE AND RELATED COMPOUNDS. A COMMENT ON THE STRUCTURE OF ′GLUT‐5(10)‐EN‐1‐ONE′ FROM EUPHORBIA NERIFOLIA

AbstractOxidation des Oleanens (I) mit dem CrO3‐Pyridin‐Komplex liefert die Titelverbindung (IIa) "sowie die Verbindungen (IIb) und (IIc) (Ausb.‐Angaben in mg).

Oxidation of primary and secondary alcohols in partially protected sugars with the chromium trioxide-pyridine complex in the presence of acetic anhydride

Oxidation of primary and secondary alcohols in partially protected sugars with the chromium trioxide-pyridine complex in the presence of acetic anhydride

Preparation of D:B-Friedoolean-5(10)-en-1-one and Related Compounds. A Comment on the Structure of “Glut-5(10)-en-1-one” from Euphorbia Nerifolia

Abstract In order to examine the structure, “glut-5(10)-en-1-one”, proposed for a new triterpene from Euphorbia nerifolia, this ketone (≡ D : B-friedoolean-5(10)en-1-one) was prepared. Oxidation of D : B-friedoolean-5(10)-ene with chromium trioxide-pyridine complex gave the allylic oxidation products, D : B-friedoolean-5(10)-en-1-one, D : B-friedoolean-5(10)-en-6-one, and D : B-friedoolean-5(10)-ene-1,6-dione. The spectral data and physical constants of the synthetic ketone (D : B-friedoolean-5(10)-en-1-one) were not identical with those of the new triterpene; this requires revision of the structure of this natural triterpene. Oxidation of D : B-friedoolean-5(10)-en-3-one enol acetate under the same conditions to give D : B-friedooleane-1,5(10)-dien-3-one is also described.

Dihydroboration of cyclic allenes

The study on the dihydroboration of a large ring cyclic allene, 1,2-cyclotridecadiene and the smallest stable allene, 1,2-cyclononadiene is described. For example, a mixture of products containing isomeric cyclotridecene, bicyclo(10.1.0)-tridecane, cyclotridecanone, cyclotridecanol, isomeric cyclic 1,2-cyclotridecandiol and isomeric 1,3-cyclotridecandiol is obtained from dihydroboration-oxidation of 1,2-cyclotridecadiene. However, dihydroboration-hydrolysis-oxidation of 1,2-cyclotridecadiene affords mainly cyclotridecanol, whereas dihydroboration-oxidation with chromium trioxide-pyridine yields mainly a mixture of Z- and E-cyclotridecene. Reasonable mechanistic pathways have been suggested for the formation of products. The proposed unusual elimination reaction of 1,2-diorganoboranes with chromium trioxide has been substantiated using an authentic 1,2-diorganoborane from diphenyl acetylene. The reaction appears to be stereospecific withthreo-diorganoborane furnishing predominantly E-alkene. The results with 1,2-cyclononadiene has also been rationalised on a similar basis.

Synthesis of 4-d1-testosterone and 4-d1-androstenedione.

In order to clarify the stereochemistry at C-4 in enzymatic saturation of Δ4-3-ketoste-roids synthesis of 4-deuterated testosterone and androst-4-ene-3, 17-dione (XVIII, XIX) has been undertaken. The key intermediate leading to the required substrate, 4α-d1-5α-androstane-3β, 4β, 17β-triol 3, 17-bis (dimethyl-tert-butylsilyl) ether (XVI), was prepared by stereospecific reduction with lithium aluminum deuteride from 3β, 17β-dihydroxy-5α-androstan-4-one disilyl ether (XIII), which was readily obtainable from androst-4-ene-3β, 17β-diol disilyl ether (XI) by hydroboration, followed by oxidation with chromium trioxide-pyridine complex. Dehydration of XVI with phosphorus oxychloride in pyridine provided the Δ4 olefine (XVIIb) which on chromium trioxide oxidation was led to the desired compounds. Reductive dehalogenation of 4-bromotestosterone silyl ether (II) with lithium aluminum deuteride and subsequent oxidation with chromium trioxide-pyridine complex afforded 4-d1-testosterone silyl ether (VII) in which the deuterium incorporation, however, proved to be unsatisfactory.

InSituAllylic Oxidations With Collins Reagent

Abstract Chromium trioxide-pyridine complex (Collins Reagent) oxidizes alcohols to aldehydes and ketones in high yield, and has been particularly effective in oxidizing acid-sensitive alcohols. A great improvement in the utility of the reagent was reported by Ratcliffe and Rodehorst who made the complex in situ in methylene chloride – thus avoiding the problems involved in isolating crystalline complex. The primary problems include keeping the crystalline complex dry; avoiding fires during addition of CrO3 to pyridine; and having to make the complex in a separate step in the first place. Dauben, Lorber, and Fullerton found that the isolated complex is extremely effective in allylic oxidations, i.e. in oxidizing olefins to enones. Shaw and Sherry also were able to oxidize alkynes to acetylenic ketones in low yields with the isolated complex. In unpublished experiments, the in situ Ratcliffe procedure was tried for allylic oxidations – but with poor yields. Shaw and Sherry reported similar problems with the...

The preparation of tritiated betulaprenols and dolichols

A rapid and simple procedure is described for the preparation of tritium-labeled polyprenols. The isoprenoid alcohols are oxidized by chromium trioxide-pyridine complex in dichloromethane and the resulting aldehydes are isolated and reduced with 3H-labeled sodium borohydride. Radioactive betulaprenols and dolichols have been obtained in high yield and purity by using this procedure.

A Facile Preparation of the Ethylene Glycol Mono-Ketal of Cyclohexane-1, 4-Dione

Abstract The ethylene glycol mono-ketal of cyclohexane-1,4-dione (4) is an exceedingly useful bifunctional synthetic intermediate. In order to prepare synthetically useful amounts of the previously reported 1 pyrrolidine enamine 5, we have developed a straightforward route which starts from cyclohexane-1,4-diol (1). We have found that oxidation of diol 1 with slightly less than 1 equivalent of Jones reagent2 gives a mixture which contains a 90% yield of the desired hydroxy-ketone 2.3 The ketal 3 could be prepared directly from the crude hydroxy-ketone 2 by the standard procedure employing ethylene glycol and benzene with minimal extractive work up. We utilize a chromium trioxide-pyridine oxidation4 of the alcohol 3 to obtain the ketone-ketal 4. This procedure circumvents the problem caused by the high water solubility of intermediates 2 and 3 which frustrate some of the previously reported preparations.

Total Synthesis of 13β-Allylgonanes. I. Synthesis of dl-17α-Ethynyl-17β-hydroxy-13β-allylgon-4-en-3-one

dl-17α-Ethynyl-17β-hydroxy-13β-allylgon-4-en-3-one (XXIV) was synthesized via 17β, 2'-epoxy pentaene (X). The double bonds at C-14 and -8 of X was hydrogenated sequentially by conventional methods. 17β, 2'-Epoxy triene (XIII) was treated with p-toluenesulfonic acid in acetic anhydride to give 13β-allylgonane (XIV) as a major product. Birch reduction of the tetrahydropyranyl ether (XIX) followed by acid treatment yielded the 4-en-3-one compound (XXI), which was oxidized with chromium trioxidepyridine complex to the 17-ketone (XXII). The enol ether (XXIII) was treated with lithium acetylide in ethylenediamine, and then with acid to yield XXIV. The progestational activity of XXIV is as potent as norgestrel.