Paul L. Coe

The synthesis and antiviral activity of 4-fluoro-1-beta-D-ribofuranosyl-1H-pyrazole-3-carboxamide.

A novel fluoropyrazole ribonucleoside has been shown to have significant anti-influenza activity in vitro. The compound is compared and contrasted with the structurally-related compound ribavirin in attempts to identify factors having significant bearing on the mode of action of both compounds.

An improved synthesis of benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-d-erythro-pentofuranoside, an intermediate in the synthesis of 4′-thionucleosides

Abstract Treatment of methyl 3,5-di- O -benzyl-2-deoxy-α,β- d - erythro -pentofuranoside with α-toluenethiol and conc. hydrochloric acid gave 3,5-di- O -benzyl-2-deoxy- d - erythro -pentose dibenzyl dithioacetal ( 21 ). Mesylation 21 and ring closure gave benzyl 3,5-di- O -benzyl-2-deoxy,1,4-dithio-α,β- l - threo -pentofuranoside. Inversion of configuration at C-4 of 21 was achieved by the Mitsunobu reaction, to produce 4- O -benzoyl-3,5-di- O -benzyl-2-deoxy- l - threo -pentose dibenzyl dithioacetal. Successive debenzoylation, mesylation, and ring closure then gave the title compound. Several new dithioacetal derivatives of 2-deoxy- d - erythro -pentose were prepared in exploratory routes to the described thio sugar or as intermediates.

Aromatic polyfluoro compounds—XXVIII : Further reactions of the pentafluorophenyl anion

The pentatluorophenyl anion from pentailuorophenyllithihium has been used as a nucleophile and as a source of tetrafiuorobenzyne. As a nucleophile it was used to make poly-lluorobiand -terphenyl derivative-s from perfluorotoluene, perfluoro-o-xylene, pcntiuoronitrobenzene and bromopentafluorobenzene, and polyfluoropolyaryls from pcrfluorobiphenyl. It also attacked decafluorocyclohexene and chlorotrifluoroethylene presumably, by an additionelimination sequence. Reactions using the tetrafluorobenzyne intcrmcdiati were carried out in the presence of excess bromopentatluorob, pentafluorobenzene and various lithium halides, in some cases with variation of the solvent. A mechanism for some of these reactions is postulated. PENTAFLUOROPHENYL-LITHIUM, previously prepared by two methods is a useful precursor in the synthesis of pentafluorophenyl derivatives.* Also, at temperatures above 0” it decomposes to give a tetratluorobenzyne intermediate. Further reactions of the pentafluorophenyl anion used both as a nucleophile and as a source of tetrafluorobenzyne are now described. In three recent communicationss-s similar reactions have been reported. The chemistry of 2-bromo-nonafluorobiphenyl, observed’ during attempts to prepare pentafluorophenyl derivatives of metals using pentafluorophenyl-lithium in etherhexane mixtures, was investigated and its structure indicated by Pe NMR. A tentative mechansim for the reactions involved was based on the formation of tetrafluorobenzyne. In our work the reaction of pentafluorophenyl-lithium with excess of bromopentafluorobenzene was lirst carried out at -40” in ether. A pale yellow ether insoluble fraction, which was mainly organic and contained Br and F, and probably a mixture of poly-phenyls, C!,,Fs(C,F~,Br was obtained together with an ether soluble fraction shown by gas chromatography to contain three components. Separation using preparative gas chromatography gave 1,2-dibromotetrafluorobenzene, 2bromononafluorobiphenyl and 4bromononatluorobiphenyl in the ratio of 1: 1: 8. The structures of these three compounds were proved unambiguously. The dibromotetrafluorobenzene was identical to that prepared by bromination of 1,2,3,4-tetrafluorobenzenea and the bromononafluorobiphenyls were synthesized independently. 1 Part XXVII, J. Chem. See. 6329 (1965). a P. L. Coe, R. Stephens and J. C. Tatlow, J. Chem. Sot. 3727 (1962). a D. E. Fenton, A. J. Park, A. G. Massey and D. Shaw, Tetrahedron letters 16,449 (1964). ’ D. E. Fenton, A. J. Park, A. G. Massey and D. Shaw, J. Organometallic Chem. 2,437 (1964). 6 N. N. Vorozhtsov Jr., V. A. Barkharsh. N. G. Iranova and A K. Petrov. Tetrahedron fetters 47, 3575 (1964). E M. Hellman, A. J. Bilbo and W. H. Pummer. J. Amer. Chem. Sot. 77,365O (1955).

Aromatic polyfluorocompounds—XLIII: Reactions of tetrafluorobenzyne with aromatic and heteroaromatic compounds

Abstract Tetrafluorobenzyne reacts with benzene, toluene, the isomeric xylenes, durene, thiophen, 1-methylpyrrole, cyclopentadiene and styrene to give Diels-Alder type adducts. In the cases where mixtures of isomers formed these have been separated and their ratios determined. The further chemistry of some of the adducts is described.

Perfluoroalkylcopper(I) compounds : II. Reactions of perfluoroalkylcopper(I) compounds and perfluoroalkyl iodide/copper mixtures with olefins

Abstract Perfluoroheptylcopper(I) with 1-heptene and 1-dodecene gives mixtures of 1-(perfluoroheptyl)heptane and 1-(perfluoroheptyl)-2-heptene and of 1-(perfluoroheptyl)dodecane and 1-(perfluoroheptyl)-2-dodecene, respectively. In similar reactions cyclohexene and cycloheptene yield only the (perfluoroalkyl)cycloalkane whereas cyclopentene yields only the olefin. Reaction with allyl bromide proceeds with double bond migration and loss of bromine. A mild copper-catalysed addition of perfluoroalkyliodides to olefins has also been discovered.

3,5-Bis(trifluoromethyl)pyrazole and some N-substituted derivatives

Abstract The pyrazoles (CF 3 ) 2 C 3 HN 2 R [R = H, COPh, C 6 F 5 , C 6 H 4 NO 2 -4 and C 6 H 3 (NO 2 ) 2 -2,4] have been prepared in yields ranging from 27% (R = C 6 F 5 ) to 78% [R = C 6 H 3 (NO 2 ) 2 -2,4] by the reaction between 1,1,1,5,5,5-hexafluoropentane-2, 4-dione and the appropriately substituted hydrazine, NH 2 NHR.

Polyfluoro diethyl and ethyl methyl ethers: their preparation using cobalt (III) fluoride and potassium tetrafluorocobaltate (III) and their dehydrofluorination

Abstract Diethyl ether has been fluorinated with CoF3 to yield a mixture from which dl -threo and -erythro 1,2-difluoroethyl 1,2,2-trifluoroethyl ether, dl and meso bis(1,2,2-trifluoroethyl) ether and dl-1,1,2,2-tetrafluoroethyl 1,2,2-trifluoroethyl ether were isolated. Fluorination with KCoF4 at ca 200° afforded ethyl 1,2,2-trifluoroethyl ether as the sole isolable product; at higher temperatures some of the above ethers were formed. Similar fluorination with CoF3 of methyl ether afforded 1,2,2-trifluoroethyl methyl ether, 1,2,2-trifluoromethyl ether, 1,2,2-trifluoroethyl difluoromethyl ether and 1,1,2,2-tetrafluoroethyl methyl ether; with KCoF4 1,2,2-trifluoroethyl methyl ether was the sole product. Dehydrofluorination, using fused potassium hydroxide, of either isomer of bis(1,2,2-trifluuoroethyl) ether gave a mixture of (E,Z,) and (Z,Z) bis(1,2-difluorovinyl) ethers and (E) and (Z) 1,2,2-trifluorethyl 1,2-difluorovinyl ethers. Similarly, 1,1,2,2-tetrafluoroethyl 1,2,2-trifluoroethyl ether yielded (E) and (Z) 1,1,2,2,-tetrafluoroethyl 1,2-difluorovinyl ether in the ratio 1:4. Dehydrofluorination of 1,2,2-trifluoroethyl fluoromethyl ether yielded (E) and (Z) fluoromethyl 1,2-difluorovinyl ethers with a trace of fluoromethyl 2,2-difluorovinyl ether.

Perfluoroalkyl)copper(I) compounds III. Reaction of (perfluoroalkyl)copper(I) compounds with aromatic hydrocarbons

Abstract (Perfluoroheptyl)copper reacts with aromatic compounds to give the corresponding perfluoroheptyl arenes. Thus benzene and p -xylene yield (perfluoroheptyl)benzene and 1-perfluoroheptyl1-2,5-dimethylbenzene respectively. Toluence and nitrobenze afford mixtures of o - and p -substituted compounds. Cholorobenze yields products derived from halogen displacement as well as the expected o/p mixture.

The synthesis and antiviral properties of E-5-(2-bromovinyl)-4′-thio-2′-deoxyuridine

A practical 7 step synthesis of benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-D-erythro-pentofuranoside from 2-deoxy-D-ribose is described and the product has been used in the synthesis of some 4′-thio-2′-deoxynucleosides which have potentially useful biological activity.

Reactions of tetrafluoroethylene oligomers. Part 1. Some pyrolytic reactions of the pentamer and hexaher and of the fluorine adducts of the tetramer and pentamer

Abstract Pyrolyses of these highly branched fluorocarbons over glass beads caused the preferential thermolyses of CC bonds where there is maximum carbon substitution. Fluorinations of perfluoro-3,4-dimethylhex-3-ene (tetramer) (I) and perfluoro-4-ethyl-3,4-dimethylhex- 2-ehe (pentamer) (II) over cobalt (III) fluoride at 230° and 145° respectively afforded the corresponding saturated fluorocarbons (III) and (IV), though II gave principally the saturated tetramer (III) at 250°. Pyrolysis of III alone at 500—520° gave perfluoro-2-methylbutane (V), whilst pyrolysis of III in the presence of bromine or toluene afforded 2-bromononafluorobutane (VI) and 2H-nonafluorobutane (VII) respectively. Pyrolysis of perfluoro-3-ethyl-3, 4-dimethylhexane (IV) alone gave a mixture of perfluoro-2-methylbutane (V), perfluoro-2-methylbut-1-ene (VIII), perfluoro-3-methylpentane (IX), perfluoro-3,3-dimethylpentane (X), and perfluoro-3,4- dimethylhexane (III). Pyrolysis of IV in the presence of bromine gave (VI) and 3-bromo-3-trifluoromethyl-decafluoropentane (XI): with toluene, pyrolysis gare VlI and 3H-3-trifluoromethyldecafluoropentane (XII). Pyrolysis of II at 500° over glass gave perfluoro-1,2,3-trimethylcyclobutene (XIII) and perfluoro-2,3-dimethylpenta-1,3(E)- and (Z)-diene (XIV) and (XV) respectively. The diene mixture (XIV and XV) was fluorinated with CoF 3 to give perfluoro-2,3-dimethylpentane (XVI) and was cyclised thermally to give the cyclobutene (XIII). Pyrolysis of perfluoro-2- (1′-ethyl-1′-methylpropyl)-3-methylpent-1-ene (XVII) (TFE hexamer major isomer) at 500° gave perfluoro-1-methyl-2-(1′-methylpropyl)cyclobut-1-ene (XVIII) and perfluoro-2-methyl-2-(1′-methylpropyl)buta-1,3-diene (XIX). Fluorination of XVIII over CoF 3 gave perfluoro-1-methyl-2- (1′-methylpropyl)cyclobutane (XX), which on co-pyrolysis with bromine gave VI. XIX on heating gave XVIII. Reaction of XVIII with ammonia in ether gave a mixture of E and Z 1′-trifluoromethyl-2-(1′-trifluoromethyl- pentafluoropropyliden-1′-yl)tetrafluorocyclobutylamine (XXI) which on diazotisation and hydrolysis afforded 2-(2′trifluoromethyl- tetrafluorocyclobut-1-en-1′-yl)-octafluorobutan-2-ol (XXII).