Difluorobenzenes, reaction

Kariv-Miller and Vajtner have successfully carried out selective defluorination of 1,3-difluorobenzene to fluorobenzene by cathodic reduction at a mercury cathode in diglyme containing Bu4NBF4 and a small amount of dimethylpyrrolidinium (DMP+) salt [6]. In this reaction, DMP+ is first reduced to form an amalgam, which reduces difluorobenzene catalytically as shown in Scheme 2.1. 

The new method of Yoneda s group132 is also a one-pot diazotization-fluoro-de-diazoniation in a liquid-liquid two-phase mixture of pyridine and hydrogen fluoride. Yields for 25 aromatic amines and diamines are 50-100%, except for 2-and 3-fluorobenzoic acid, the three nitroanilines, 3- and 4-diaminobenzene and 4,4 -diaminodiphenyl-oxide (10-50%). In their 1994 paper the authors demonstrate that, in the same system, the photochemical decomposition gives in many cases significantly higher yields than the thermal reaction. The most spectacular increase in yield was found for the fluorination of 2-fluoroaniline where o-difluorobenzene was obtained photochemically in 80.2% yield, but thermally only in 0.6% ... 

Less complex non-conjugated diene systems also lead to cubane-like derivatives as in the diene 175. Here the outcome of the reaction is dependent upon the excited state. Thus, direct irradiation brings about fragmentation with the formation of 1,4-difluorobenzene and excited-state naphthalene while triplet-sensitized irradiation follows a different path with the formation of the cage compound 17682. 

Electrophilic substitution in benzo[fe]thieno- and benzo[fe]furo-[2,3-c]pyridines (2) occurs mainly at the 6-position, although when this position is blocked by Cl in a related structure 5-,7-, and 8-substituted products are formed. The usefulness of triflu-oromethanesulfonic acid as a new solvent with CFCI3 for the reaction of fluorine with aromatics has been explored. Fluorobenzene gives 1,4-difluorobenzene (31%) and 1,2-difluorobenzene (7%) instead of the addition products mainly observed when the acid is absent 1,2- and 1,3- but not 1,4-difluorobenzene undergo further substitution at appropriate acidity. 

Many of these attachment reactions are also diffusion-controlled in other solvents of low electron mobility like, for example, n-hexane. It has been suggested that this is the case for all solvents for which 1 cm /Vs [118]. For this to be true, the rate constant k should scale as the mobility. For hexane, the rate constants for attachment to solutes like biphenyl, naphthalene, and difluorobenzene are close to 1 x 10 sec or one-third the value in cyclohexane. The mobility in -hexane is approximately one-third that in cyclohexane [2] thus k scales with fijj for these two solvents. 

Yet another piperidine-based antipsychotic agent replaces the butyrophenone or diarylpropyl function found in earlier compounds by a benzopyrimidine group. The synthesis starts by the conversion of the carboxylic acid in piperidine (22-1) to its acid chloride. Reaction with 1,3-difluorobenzene (22-2) in the presence of aluminum chloride affords the acylated product (22-3). Reaction with hydroxylamine leads to the corresponding oxime (22-4). Treatment of that derivative with a base... 

Polyfluorobenzenes were the first compounds to be shown to undergo a rather unusual gas-phase reaction. Typical examples (93, 94) involve alkoxide ions (Briscese and Riveros, 1975). In (93) the relative yields of C6H4FO for different isomers of difluorobenzene are influenced by the alkyl group (R) since the different isomers display acidities comparable to the aliphatic alcohols. Reaction (93) is particularly important for p-difluorobenzene, the least... 

In comparison with reaction in neat Et3N 3HF, benzene in a 1 mol/1 solution of Et3N 2.9HF in acetonitrile, electrolysed at 2.5 V (vs Ag/Ag+) produced 35% fluorobenzene, together with 4.8% difluorobenzene and 0.6% 3,3,6-tri-fluoro-1,4-cyclohexadiene. 

First, pellets of the diazonium tetrafluoroborate are spread on a cylindrical nickel roll, internally heated with Dowtherm.202Iftheroll is heated 100 to 150°C above the decomposition temperature, the diazonium tetrafluoroborate is decomposed within 10 to 25 seconds. If the temperature is nearer to the decomposition point, decomposition requires around 30 minutes. The roll speed is adapted to the reaction time. The roll surface is regenerated by a doctor blade which scratches off the residues. In this way, 4-chloro-l,2-difluorobenzene was obtained in 36 % yield from 4-chloro-2-fluorobenzenediazonium tetrafluoroborate at 290-310 C within 10 to 25 seconds. 

Fluorobenzene and other fluoroarenes as well as meta- and /wa-disubstituted fluorohaloben-zenes can be reacted with thiols, yielding monosubstituted products t only 1,4-difluorobenzene yields predominantly the dithiolated product. The reactions require high temperatures, often long times and highly polar solvents, preferably hexamethylphosphoric triamide. 

The use of photochemical dinitrogen loss has been selectively employed in similar reactions with some notably enlightening results [124,125]. An early study shows that Cp Re(CO)(L)(N2) (L is P(OEt)3, P(OMe)3, PMe2Ph) photochemically produces frans-Cp Re(CO)(L)(Ph)Cl under UV irradiation in chlorobenzene, similar to the reports above [124]. However, the analogous reaction of Cp Re(CO)2(N2) with 1,4-difluorobenzene, produces both the C-H oxidative addition product Cp/Re(CO)2(Ar)H (Ar is 2,5-C6F2H3) and the coordinated benzene product, Cp Re(CO)2( 2-l,4-C6F2H4) [125]. The two isomers interconvert around 213 K. 

From these data it can be pointed out that for a given size of the clusters the proton affinity of water is smaller than for the other solvents consequently, for fluorobenzene/methanol or para-difluorobenzene/water systems, a proton affinity of 205/215 kcal mol-1 seems to be the limit of the reaction process (it is reached for two molecules of methanol and three molecules of water). 

Carbon-boron clusters ( carboranes ) have been shown to react with Cr-coordinated halo-arenes. For example, reaction of 2 equiv. of LiC2BjoHio(CH3) with para-difluorobenzene-tricarbonylchromium complex in refluxing THF results in the displacement of both fluoride substituents from the arene ring to yield the para-phenylene compound, albeit in just 9 % yield owing to the effect of the steric bulk of the carborane [55]. 

The reaction seems to proceed through a radical mechanism. Small amounts of difluorides and o-fluorinated products are obtained as byproducts in the reactions of (4-/cr/-butylphenyl)-trimethylsilane and (4-chlorophenyl)trimethylsilane (X = t-Bu and Cl). The yield of o-fluo-rinated compounds increases in the case of (4-methoxyphenyl)trimethylsilane (39%, X = OMe). 1,4-Difluorobenzene (35%) is formed in the reaction of trimethylphenylsilane (X = H) with xenon difluoride. 

A process for the preparation of fluorobcnzencs comprises the heating of fluorobenzaldehydes in the presence of a catalyst. Suitable catalysts are transition metals from the B groups 1, 11. VI. VII and VIII. The best catalytical properties seem to be held by rhodium and the metals of the platinum group, e.g. formation of 1.3-difluorobenzene (5). The reaction maybe carried out in homogeneous solution with soluble rhodium catalysts (Wilkinson s catalyst) or in heterogeneous phase with the catalyst fixed on a carrier. ... 

Modified high-silica zeolites are used for selective oxidation of mono- and difluorobenzenes into corresponding fluorophenols using nitrous oxide as an oxidant. The nature of the active sites and the reaction mechanism are discussed. 

In the case of difluorobenzenes, the reaction scheme is similar to the above-discussed one for monofluorobenzene oxidation. The regioselectivity of the reaction is governed by the cooperative mesomeric and inductive effects of two fluorine atoms and the product distribution lends further support for the mechanism of electrophilic substitution. 

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