Fluoro-substituted compounds

The products obtained in the reaction of A -cyclopropyl-4,5-difluoroanthranilic acid hydrazides 429 with triphosgene were dependent on the steric hindrance imposed by substituent R at position 3, and not the electronic effect of this group. While the unsubstituted compound 429 (R = H) gave exclusively the 4-hydrazono-3,l-benzoxazin-2-one-type product 430, the similar reactions of the chloro-, methyl-, and methoxy-substituted analogs 429 (R = Cl, Me, OMe) resulted in formation of the corresponding quinazoline-2,4-diones 431 as the sole products. For the fluoro-substituted compound 429 (R = F), a 20 80 mixture of the products 430 and 431 was obtained (Equation 46) <2005JHC669>. 

It has been found that F-Teda BF4 (6) transforms chiral and optically pure ft-oxo sulfoxides into the corresponding a-fluoro-substituted compounds 30 without affecting the chiral sulfinyl group.106... 

Chiral Sulfoxides in the Synthesis of Optically Pure Fluoro Substituted Compounds of Biological Interest ... 

Electron with drawing groups like F, CFs and NO2 on the benzyl substituent favor reducibility. The fluoro substituted compound 12 is reducible only competitively with water since its first wave appears as a shoulder on the solvent wave. 

Thermal dimerization of perfluoroalkcnes is also a good approach for obtaining interesting dimeric fluoro-substituted compounds. A -[4-Phenoxy-3-(trifluorovinyl)phenyl]phthalimide (3), which is a model for polyimides containing trifluorovinyl groups, undergoes thermal dimerization at 140-160"C to give predominantly the trtf .s-1,2,3,3,4,4-hexafluoro-l,2-bis(2-phenoxy-5-phthalimidophenyl)cyclobutane (4).6 See Section 2.1.1.6.2. for a more detailed discussion of this [2 + 2]-cycloaddition process. 

Use of l,2-bis(chlorosulfenyl)tetrafluoroethane (327) even allows the synthesis of 4,4,5,5-tetra-fluoro-substituted compounds (328) (Equation (67)) <86CZ417,86RRC935,87ZAAC(545)143>. 

Jcc and Jhc couplings have been determined for a set of 2-fluoro- and 3-fluoro-substituted thiophenes, pyrroles and furans. Invariably, a dramatic increase in the Jc2C3 couplings has been observed in 2-fluoro- and 3-fluoro-substituted compounds in comparison with those measured for the parent compounds. The same is valid for Jc3C4 measured in 3-fluoro derivatives. The experimental J values have been well reproduced by the DFT calculated ones. 

The p a values of the four carboxylic acids shown on page 66 decrease (become more acidic) as the electron-withdrawing ability (electronegativity) of the halogen increases. Thus, the fluoro-substituted compound is the strongest acid because its conjugate base is the most stabilized (is the weakest). 

Some classes of fluoro-substituted compounds have those features and are the main components of practical liquid crystal mixtures for use in sophisticated displays like active-matrix liquid crystal displays (LCDs). 

Methylmagnesium chloride has been added to various d-(4-substituted-phenyl) <5-oxo esters 15 (X = H, Cl 13, F, Cl, Br, OC11,) which provides the diastereomeric -lactones 1642. The electronic properties of the phenyl 4-substituent have no significant influence on the diastereoselectivity. Except for the 4-methoxyphenyl compound, which is unreactive even at 60 °C, a ratio of ca. 40 60 in favor of the anti-Cram product is observed at 60 "C in tetrahydrofuran as reaction solvent. Lowering the reaction temperature to 0 °C slightly increases the anti-Cram selectivity in the case of the 4-fluoro-, 4-chloro-, and 4-bromo-substituted compounds. On the other hand, a complete loss of reactivity is observed with the <5-phenyl- and <5-(4-methylphenyl)-substituted h-oxo esters. 

Tram-anular interactions, which would create an active radical site via hydrogen transfer through 98, cannot be invoked to explain the specific loss of a CH3 radical from the ether side chain. This conclusions is based upon the following experimental observations. The radical cation of the tetrafluoro substituted compound 101 eliminates CH3, but loss of CH3 from the para-isomer 102 is not observed. If a transanuiar process according to 97- 98 were operative, then such a reaction is not expected to be suppressed upon substitution of H by F as is known for many examples from the field of photochemistry of fluoro substituted compounds41 (23). 

Aldimines, Ketimines, and Related Compounds as Dipolarophiles Reactions of aldimines with nitrile oxides proceed readily to give 1,2,4-oxadiazolines independently of the nature of substituents both in dipole and dipolarophile molecules. 1,2,4-Oxadiazolines were prepared by the regiospe-cihc 1,3-dipolar cycloaddition of nitrile oxides with fluoro-substituted aldimines (295). Phosphorylnitrile oxides gave with azomethines, PhCH NR, phosphory-lated 1,2,4-oxadiazolines 129 (296). Expected 1,2,4-oxadiazolines were also obtained from azomethines, derived from 4-formylcoumarine (179) and 1,3-diphenylpyrazole-4-carbaldehyde (297). 

An irreversible dyotropic rearrangement of fluoro-substituted tris(silyl)hydroxyl-amines (127) (128) has been reported and ab initio and density functional calculations for model compounds have confirmed the dyotropic course of this rearrangement. ... 

Direct modification has also been applied to the synthesis of fluoro-substituted amikacin (Scheme 4.21). Utilizing the metal-chelating protocol and the steric hindrance of 5-OH, fluorination was carried out selectively at the 5-OH. Two compounds (132 and 133) were found to have similar trends of antibacterial activity (Table 4.11). However, the activities of amikacin, 132 and 133, against E. coli (ANT(2")) were found to be much higher than those reported in Table 4.10 regardless of the sites of deoxygenation. We believe that the results from Table 4.11 may better explain the trend of structure activity relationship... 

The fluoro substituents proved to induce changes in the reactivities of the methyl- (X = H) and trifluoromethyl-substituted (X = F) pyrido[3, 2 4,5]furo[3,2- [l,3]oxazin-4(47r)-ones 105 with nucleophiles. When methyl-substituted compounds 105 (X = H) were reacted with piperidine in toluene, Wacetylamino carboxamides 106 were formed by nucleophilic attack at the carbonyl group of the l,3-oxazin-4-one ring (Scheme 16). However, the similar reactions of the trifluoromethyl-substituted analogs 105 (X = F) resulted in formation of amidino carboxylic acids 107 by attack at electron-poor position 2 <1995JFC(74)1>. 

Methylene-l,3-benzoxazin-2-ones 194 were found to be susceptible to addition to the exocyclic double bond. On heating under reflux in ethanol, oxazinones 194 were transformed to the 4-ethoxy derivatives 195. Treatment of 194 with l-chloromethyl-4-fluoro-l,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA-BF4), an electrophilic fluorinating reagent, in the presence of methanol, led to the 4-fluoromethyl-4-methoxy-substituted compounds 196 (Scheme 34) <2003T8163>. 

Fluoro-substituted dihydrofuro[3,2-r ]pyridinones are obtained from the thermolysis reaction of cyclopropa[3]-furo[2,3-f]pyrroles, 134, along with the loss of HF (Equation 67) <2005SL1006>. Compound 134 is generated from pyrroles via reaction with a carbene to give an azomethine ylide which undergoes an electrocyclization reaction. 

Similar decomposition is observed in p-bromoacetophenone, o-bromo-, p-bromo, and p,p -dibromobenzophenone, and p-iodobenzophenone44 but not in the fluoro- and chloro-substituted compounds. This order of reactivity follows the bond dissociation energies for aromatic halides which are about 90 kcal/mole for chlorobenzene, 70 kcal/mole for bromobenzene, and 60 kcal/ mole for iodobenzene. The lowest-lying triplet of p-bromoacetophenone is 71.2 kcal45 while that of the substituted benzophenones is slightly lower since benzophenone itself has a lower triplet energy than acetophenone. p,p Dibromobenzophenone was the least reactive of the compounds that photoeliminated halogen atoms. 

In a series of diphenylpolyenes with a dimethylamino donor group attached to one phenylene ring and a penta-fluoro substitution on the other phenylene acting as an electron acceptor (d.6-8), the position of the 2PA peak shifts to longer wavelength and the cross section increases from 1.2 to 5.0 X 10 GM as the number of double bonds is increased from one to three (Table 4) [115]. This increase in cross section with the addition of double bonds is slightly larger for this series of dipolar diphenylpolyenes than for the centrosymmetric q.2, q.6, q.7 discussed earlier (from 2.0 to 3.2 X 10 GM). However, compounds d.6-8 have very low fluorescence quantum yields (2-3%), so their use in applications based on induced fluorescence could be limited. 

Replacement of tppts by the fluoro substituted sulfonated ligand 4 [Table 2 94% (n=l) and 6% (n=0)] in the rhodium-catalysed hydroformylation of 1-hexene in a two phase system increased the selectivity to linear aldehyde n-heptanal from 86% to 93% at the low P/Rh molar ratio of 7.5/1.75,76 The Rh/4 catalyst was quantitatively recovered after the reaction by simple decantation.75,76 The moderate increase of the n/i ratio is of interest when one considers that ligand 4 is mainly present as the disulfonated species (94%) compared to the trisulfonated compound tppts and that tris(4-fluorophenyl)phosphine is less basic (pKa=1.97) than triphenylphosphine (pKa=2.73).376 In rhodium-catalysed hydroformylation reactions in organic solvents it is known that electron withdrawing substituents, which increase the -acidity of the ligand, give rise to an increase in the n/i ratio.377 379... 

Diazo and Diazonium Compounds Fluoro-Substituted Aliphatics... 

A number of cycloalkyl-, vinyl-, aryl-, and benzyllithium compounds (predominantly benzyl-lithiums) are converted into fluoro derivatives in good to excellent yields, e.g. formation of 4, 5, and 6 19 however, when this method was applied to the synthesisof 3-fluorobenzocyclobutene from the lithium salt a violent explosion occurred when the reaction mixture was warmed from — 70 C to room temperature.20 Various fluoro-substituted thiophenes 7 are obtained when the starting compounds (thiophene, 2-methylthiophene, etc.) arc transformed with al-kyllithium compounds to the corresponding lithium derivatives then fluorinated with perchloryl fluoride at 0 C.21 Potassium tricyanomethanidc is converted at —15 C in triglyme into tricyanofluoromethane in 81 % yield.22... 

Trialkylaryltin derivatives 30 are converted into fluoro-substituted derivatives 31. 37-38 (4-Mcth-oxyphenyl)trimethylsilane (32) in acetonitrile gives 4-fluoroanisole and (3-fluoro-4-meth-oxyphenyl)trimethylsilane in the ratio 1 2. A -Methyldiethanol esters of arylboronic acids 33 (l-aryl-5-methyl-2,8-dioxa-5-azonia-l-boranuidabicyclo[3.3.0]octanes) are converted into tluoroaromatic compounds with cesium fluoroxysulfate in acetonitrile in the presence of 1,3-dinitrobenzene at room temperature.39-40 Regiospecific synthesis of 2-fluoro-3-0-methyles-trone in 27 % yield occurs upon fluorination of the corresponding arylboronic acid with cesium fluoroxysulfate.41... 

The general method for the preparation of organo-fluorine compounds from halides and sulfonates using anhydrous TBAF suffers from the fact that wherever possible an elimination reaction occurs decreasing the yield of the fluoro-substituted product. Traces of moisture present in anhydrous TBAF induce the formation of a hydroxy-substituted product. 1-Bromooctane... 

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