The synthesis and transition temperatures of benzoate ester derivatives of 2-fluoro-4-hydroxy-and 3-fluoro-4-hydroxybenzonitriles

The synthesis and the liquid-crystal temperatures of sixty 4-cyano-2-fluorophenyl and 4-cyano-3-fluorophylen 4-substituted benzoates are described. The nematic-isotropic liquid transition temperatures of the most of these novel esters are only marginally lower than those of the corresponding esters containing an H-atom in place of the F-substituent. In several instances, the clearing points of the F-substiuted-phenyl esters are higher than those of the non-substituted-phenyl esters. The nematic ranges of several of the new esters are markedly broader than those of the analogous non-F-substituted-phenyl esters.     

Synthesis and antibacterial activity of 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids and their 6,8-difluoro analogs

Alkylation of 6,7-difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester with substituted-benzyl chlorides gave 1-(substituted-benzyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl esters. Their treatment with piperazine or N-methylpiperazine in pyridine yielded 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(l-piperazinyl)quinoline-3-carboxylic acid ethyl esters which were hydrolyzed with aqueous sodium hydroxide and then acidified with hydrochloric acid afforded the desired 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-iperazinyl)quinoline-3-carboxylic acids. The 6,8-difluoro analogs were prepared similarly using 6,7,8-trifluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester as a starting material. Some of these quinolones demonstrated fairly good antibacterial activities. Among them, 6-fluoro-1-(4-fluorophenylmethyl)-1,4-dihydro-7-(1-iperazinyl)-4-oxoquinoline-3-carboxylic acid ( 7d ) and 6,8-difluoro-1-(3-fluorophenylmethyl)-1,4-dihydro-7-(1-piperazinyl)-4-oxoquinoline-3-carboxylic acid ( 8c ) are two of the best.     

Ferroelectric Liquid Crystals. Part 9. Laterally substituted phenyl benzoates incorporating a trans-1,4-disubstituted cyclohexane ring

About 65 diverse phenyl benzoates incorporating a trans-1,4-disubstituted cyclohexane ring and at least one lateral substituent have been synthesised. The dependence of the liquid-crystal transition temperatures of these materials on various lateral substituents (F, Cl, CN, and Br) in different positions of the esters has been investigated systematically. The influence of up to four F-atoms in various positions of a standard ester has been thoroughly studied and the optimum combination for a broad smectic C mesomorphic range established. In consequence, three homologous series incorporating the 4-alkoxy-2,3-difluorobenzoic-acid moiety were prepared. An additional C?C bond was introduced into the alkyl chain attached to the cyclohexane ring of some of these esters and the resulting modifications of the transition temperatures determined. Three ester series incorporating a lateral substituent and the optically active (+)-(S)-(1-methylheptyl)oxy substituent have also been synthesised, and similar effects have been observed. These materials can be used as important components of commercial chiral smectic C mixtures for electro-optic display device applications.     

An intramolecular cyclization of 7-substituted 6-fluoro- 1,8-naphthyridine and -quinoline derivatives

A synthesis of 1,4-oxazine and pyrazine ring systems by an intramolecular cyclization of 7-substituted 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine and -quinoline derivatives having a nitrogen or oxygen nucleophilic site in the C-7 appendage was studied. The in vitro antibacterial activities of compounds prepared by this method were tested.     

Synthesis and antibacterial activity of some 7-substituted 1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids: Ethers,secondary amines and sulfides as c-7 substituents

A series of 7-substituted 1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared from 1-ethyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 8 . Those derivatives reported contain acyclic and heterocyclic substituents linked to the quinolone C-7 position via O, NH or S. The in vitro antibacterial data of some of these derivatives against 4 Gram positive and 4 Gram negative organisms are reported.     

A facile one-pot synthesis of α-fluoro-α,β-unsaturated esters from alkoxycarbonylmethyltriphenylphosphonium bromides

A convenient one-pot synthesis of α-fluoro-α,β-unsaturated esters from ethoxy- and tert-butoxycarbonylmethyltriphenylphosphonium bromide was developed. The fluorinated phosphoranes, generated in situ from alkoxycarbonylmethyltriphenylphosphonium bromides and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor^®), undergo a Wittig reaction with aldehydes to yield α-fluoro-α,β-unsaturated esters with (Z)-selectivity.     

The Synthesis and Liquid-Crystal Transition Temperatures of Some Fluoro-Substituted Benzonitriles

Various laterally fluoro-substituted benzonitriles have been prepared containing a trans-4-(n-alkyl)cyclohexane ring linked to the 4-position of the benzonitriles either through a methyleneoxy (? CH₂O–) or an ethylene (? CH₂CH₂-) bridge. The bridging group links the benzonitrile and cyclohexane rings either directly or through an additional 1,4-bonded cyclohexane or benzene ring. The synthesis and liquid-crystal transition temperatures of these new compounds are described. In several cases the nematic-isotropic transition temperatures of F-substituted benzonitriles are found to be higher than those of the non-laterally substituted analogues.     

Ferroelectric Liquid Crystals. Part 2. Chiral phenyl benzoates incorporating a trans-1,4-disubstituted cyclohexane ring

About forty novel phenyl benzoates also incorporating a trans-1,4-disubstituted cyclohexane ring and a chiral centre have been prepared. The dependence of the liquid-crystal transition temperatures of this new class of compounds on lateral substituents, diverse central linkages, chain lengths, and position of the chiral centre has been studied systematically. The synthesis and liquid-crystal transition temperatures of these new compounds are described in detail.     

Synthesis,pharmacokinetics, and biological activity of a series of new pyridonecarboxylic acid antibacterial agents bearing a 5-fluoro-2-pyridyl group or a 3-fluoro-4-pyridyl group at N-1

The 1-(5-fluoro-2-pyridyl) or 1-(3-fluoro-4-pyridyl) group was introduced in the syntheses of new pyridonecarboxylic acid antibacterial agents. 1-(5-Fluoro-2-pyridyl)-6-fluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxoquinolone-3-carboxylic acid 7b (DW-116) showed a moderate in vitro antibacterial activity but it was found to have very excellent pharmacokinetic profiles so that 7b (DW-116) showed dramatic increased in vivo efficacy.     

Consecutive catalytic electrophilic fluorination/amination of β-keto esters: toward α-fluoro-α-amino acids?

Monofluorination of β-keto esters with Selectfluor^® (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate)) using CpTiCl₃ as a catalyst, followed by amination with diazodicarboxylates using a Cu/Ph-Box catalyst leads to α-fluoro-α-hydrazino-β-keto esters in good yields and good selectivities (ee up to 94%).     

A new synthetic route to 7-halo-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid,an intermediate for the synthesis of quinolone antibacterial agents

Starting from m-fluorotoluene, 7-chloro-6-fluoro- and 6,7-difluoro-1-cyclopropyl-1,4-dihydro-4-oxoquino-line-3-carboxylic acids, 3 and 16 were synthesized. Compounds 3 and 16 are useful intermediates for the synthesis of a class of quinolone antibacterial agents. The synthetic route involves two processes; i) construction of the quinoline ring by an intramolecular cyclization accompanied by the elimination of a nitro group and ii) introduction of fluorine atom by replacement of a nitro group with potassium fluoride. 7-(3-Amino-1-pyrroli-dinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (18) was prepared from 3 or 16. The antibacterial activity of 18 compares favorably with that of ciprofloxacin (2) .     

Three-component cyclization of hydroxylamino-substituted quinoline with reactive methylene compounds and formaldehyde: new method for the synthesis of 7-(isoxazolidin-2-yl)-6-fluoroquinolones

A one-step procedure was developed for the synthesis of new 6-fluoro-7-(isoxazolidin-2-yl)-4-oxo-1,4-dihydroquinolines. The procedure is based on the 1,3-dipolar cycloaddition of the azomethine oxide and 1,1-disubstituted alkenes, which are generated in situ from 6-fluoro-7-hydroxylamino-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and CH-active compounds (dialkyl malonates, ethyl acetoacetate), respectively, in the presence of formaldehyde at 100—120 °C.     

Synthesis and antibacterial activity of new 5-substituted 1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids

The 5-hydroxymethyl and the 5-formyl-1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids have been prepared via a 5-trimethylsilyl group and were tested in vitro as potential antibacterials.     

Vibrational spectra of 2-fluoro-5-nitro-, 2-fluoro-4-nitro-, 4-fluoro-2-nitro- and 5-fluoro-2-nitrotoluene

The mid- and far-IR absorption spectra of four substituted toluenes, namely 2-fluoro-5-nitro-, 2-fluoro-4-nitro-, 4-fluoro-2-nitro- and 5-fluoro-2-nitrotoluene were recorded. Vibrational assignments are proposed assuming C_s, symmetry for the molecules.     

Differences in the coordinating ability of water,perchlorate and tetrafluoroborate toward copper(I). The x-ray crystal structures of [Cu(1,4-thioxane)3OClO3], [Cu(1,4-thioxane)3OH2]BF4 and [Cu(1,4-thioxane)4BF4

Summary Crystal structure determinations of the non-isomorphous salts, Cu(1,4-thioxane)₃(ClO₄) and Cu(1,4-thioxane)₄(BF₄) were carried out. The former compound was shown to contain strongly coordinated perchlorate while the later contains ionic tetrafluoroborate. For the coordinated perchlorate group, Cu-O is 2.278(8) Å. A third compound, Cu(1,4-thioxane)₃(H₂O)(BF₄), was also characterized by x-ray crystallography, and contains a coordinated water molecule (with Cu-O 2.234(7) Å) that is hydrogen bonded to ionic tetrafluoroborate. All three complexes have approximately tetrahedral geometry. The copper(I) atom is coordinated to the sulfur atoms of the 1,4-thioxane rings. In each of the complexes, one of the 1,4-thioxane six-membered rings is coordinatedvia an equatorial ring position and the remaining two or three rings are coordinatedvia an axial position. The compound, Cu(1,4-thioxane)₄(ClO₄), was also prepared and found to be isomorphous with Cu(1,4-thioxane)₄ (BF₄), enabling a comparison to be made between the i.r. spectra of ionic and coordinated perchlorate in similar complexes.     

Fluorinated heterocyclic compounds. 4-fluoro-2-pyridone

The uracil analog, 4-fluoro-2-pyridone was synthesized by ether cleavage of 4-fluoro-2-methoxypyridine with trimethylsilyl iodide. Improved procedures for the preparations of 2-methoxypyridine N-oxide hydrochloride and 2-methoxy-4-nitropyridine N-oxide are described.     

A regiospecific synthesis of 1-methylamino-6-fluoro-7-(4-methylpiperazin-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

An efficient and regiospecific synthesis of 1-methylamino-6-fluoro-7-(4-methylpiperizin-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ( 3 ) via an intramolecular nucleophilic displacement cyclization reaction is reported.     

The effect of lateral fluoro-substitution on the liquid crystal behaviour of some 4'-alkylphenylethyl- and trans-4'-alkylcyclohexylethyl-4,4'-disubstituted biphenyls

Abstract

The preparation of several 4'-alkylphenylethyl- and trans-4'-alkylcyclohexyl-ethyl-4,4'-disubstituted biphenyls and their 2-fiuoro derivatives is described and their transition temperatures are reported. The effect on the transition temperatures caused by the replacement of a cyclohexane ring by a benzene ring and the effect of fluoro-substitution on nematic, smectic A and smectic B thermal stabilities is discussed. In these systems, and in others, when the lateral fluoro-substituent points towards the longer terminal aliphatic unit (alkyl or alkylcyclo-hexylethyl) it causes a greater depression of smectic properties.     

Polyesters containing bicyclo[2.2.2]octane and bicyclo[3.2.2]nonane rings

Polyesters containing bicyclo[2.2.2]octane and bicyclo[3.2.2]nonane rings are prepared from 1,4-bis(carboethoxy)bicyclo[2.2.2]octane, 1,4-bis(hydroxymethyl)bicyclo[2.2.2]-octane and the 1,5-disubstituted bicyclo[3.2.2]nonane analogs. These polyesters are compared to the related polymers containing 1,4-phenylene and trans-1,4-cyclohexylene rings in terms of their melting point, thermal stabilities and oxidative stabilities. The lower symmetry of the bicyclo[3.2.2]nonane ring produces lower-melting polymers than the other ring systems. The remaining three rings are approximately equivalent in their effect on the melting point of a polymer provided that no more than one bicyclo[2.2.2]octane ring is present per polymer repeat unit. Two such rings produce a highermelting polymer than any other combination. Both the thermal and oxidative stabilities of the polyesters is improved by the presence of the bicyclo rings. This is attributed to the rings providing an approximation of a ladder polymer.     

Smectic liquid crystals. VIII. Some new laterally substituted smectic C compounds

Abstract

The synthesis and liquid crystal transition temperatures of a new class of compounds incorporating a trans-1,4-disubstituted cyclohexane ring have recently been reported. Many of these novel materials exhibit an enantiotropic smectic C mesophase over a wide temperature range and are suitable for commercial display device applications. The influence of several lateral substituents in various positions on the liquid crystal transition temperatures of these compounds has now been investigated systematically. A linear relationship between the size of the lateral substituent and the magnitude of the transition temperatures of various liquid crystal mesophases has been established for several of the series synthesized. A number of series incorporating a lateral substituent and an optically active centre have also been prepared and similar effects have been found.