Fluorination nitro compounds

The most common types of aryl halides in nucleophilic aromatic substitutions are those that bear- o- or p-nitro substituents. Among other classes of reactive aryl halides, a few merit special consideration. One class includes highly fluorinated aromatic compounds such as hexafluorobenzene, which undergoes substitution of one of its fluorines on reaction with nucleophiles such as sodium methoxide. 

The potassium siilts of nitro compounds are fluorinated on treatment v/ilh FCIO, but k is... 

The heterobimetallic asymmetric catalyst, Sm-Li-(/ )-BINOL, catalyzes the nitro-aldol reaction of ot,ot-difluoroaldehydes with nitromethane in a good enantioselective manner, as shown in Eq. 3.78. In general, catalytic asymmetric syntheses of fluorine containing compounds have been rather difficult. The S configuration of the nitro-aldol adduct of Eq. 3.78 shows that the nitronate reacts preferentially on the Si face of aldehydes in the presence of (R)-LLB. In general, (R)-LLB causes attack on the Re face. Thus, enantiotopic face selection for a,a-difluoroaldehydes is opposite to that for nonfluorinated aldehydes. The stereoselectivity for a,a-difluoroaldehydes is identical to that of (3-alkoxyaldehydes, as shown in Scheme 3.19, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

The authors of primary Reference 80 present their own and selected literature values for the R—NO bond enthalpies for the hydrocarbyl cases of Me, Et, t-Bu, allyl and benzyl, as well as mixed fluorinated, chlorinated methyl radicals. We now wish to compare nitroso species with the corresponding amino and nitro compounds. Choosing what we consider the most reliable and relevant nitroso compound data, and accompanying them with the corresponding radical data, we derive enthalpies of formation of gaseous nitrosomethane, 2-methyl-2-nitrosopropane and o -nitrosotoluene81 to be 65 2, —29 4 and 174 7 kJmol-1. (By comparison, the earlier values recommended8 for nitrosomethane and 2-methyl-2-nitrosopropane were 70 and —42 kJmol-1 respectively.)... 

Aromatic nitro compounds can be converted to the corresponding 4-fluoroanilines if the 4-position carries a hydrogen atom. Thus, nitrobenzene can be converted to 4-fluoroaniline with 100% conversion and 95% selectivity by heating with hydrogen under pressure [platinum(IV) oxide catalyst] in the presence of boron trifluoride-diethyl ether complex at 42°C for 12.5 hours. 3-Chloro-l-nitrobenzene can be similarly hydrogenated-fluorinated to 3-chloro-4-fluoroaniline.25,26... 

Fluorinated aromatic hydroxylamines can be selectively oxidized to the corresponding nitroso-benzenes 8 using iron(III) choridc as the oxidizing agent.248 The hydroxylamine is prepared in situ from the nitro compound.248... 

Nucleophilic aromatic substitution of the fluorine substituents by benzene-dithiolate sulfur atoms (step a), reduction of the nitro compound (step b), diazotization, reaction with KSaCOEt, alkaline hydrolysis, and acidification gave tpS4 H2 (step c). It could be purified via the [Ni(tpS4)]2 complex (Fig. 1), which is readily hydrolyzed with dilute hydrochloric acid to give pure tpS4 H2. 

Nevertheless, nucleophilic displacement of an activated aromatic nitro group by fluoride is much more common and constitutes an efficient method of linking fluorine to an aromatic ring. The availability and low cost of nitroaromatics make fluorodenitration an attractive alternative to halogen exchange for the synthesis of selectively fluorinated aromatic compounds via nucleophilic fluorination. Various salts, such as rubidium [ F]fluoride, - tctrabutylam-monium fluoride, or potassium fluoride. can be used as fluoride sources. 

Hydrogen in fluorinated aromatic compounds can be substituted by the nitro group by the following well-known procedure. ... 

Difunctional compounds, including certain halogenated ethers, aldehydes, ketones, phenols, amines, and nitro compounds, have been prepared by the Sandmeyer reaction. However, fluorophenols and fluoro acids are best obtained from the corresponding ethers and esters, respectively, which have been fluorinated by the Schiemann reaction. ... 

Class II Other liquids composed of molecules containing both active hydrogen atoms and donor atoms (oxygen, nitrogen, and fluorine)—e.g., alcohols, acids, phenols, primary and secondary amines, oximes, nitro compounds with alpha-hydrogen atoms, nitriles with alpha hydrogen atoms, ammonia, hydrazine, HF, HCN (plus nitromethane, acetonitrile even though these form 3-dimensional networks they have weaker bonds than —OH and —NH bonds in class I)... 

Fluorinated aromatic compounds. Finger and Kruse found that an aromatic chlorine or bromine atom activated by an o- or p-nitro group is subject to nucleophilic displacement by fluoride ipn on reaction with potassium fluoride in solvents such as succinonitrile, dimethyl formamide, or dimethyl sulfoxide. Unpublished work at Olin Mathieson Chemical Corporation indicates that best results are obtained with dimethyl sulfoxide as solvent and with potassium fluoride that has been finely ground (<100 mesh) and dried in a vacuum oven at 100° for at least 4 hrs. prior to use. In a typical case a mixture of p-nitrochlorobenzene, potassium fluoride, and dimethyl sulfoxide is stirred under reflux at 180° for 8-9 hrs., the cooled mixture... 

The destabilization of sp -bound fluorine by p-jt repulsion activates fluorinated aromatic compounds totvard nucleophilic attack and subsequent substitution. The susceptibility of the carbon center toward nucleophiles is also enhanced by the negative inductive (—T) effect of fluorine. In particular, if the aromatic compound is also activated by —M electron-withdrawing substituents, for example a nitro or cyano group, in the ortho or para positions the fluorine is easily replaced by a variety of nucleophiles even under very mild conditions via a resonance stabilized Meisenheimer complex (Scheme 2.39). The ease of nucleophilic halogen replacement - F > Cl > Br > I - is in the opposite order to that for aliphatic nucleophilic substitution. 

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