Activated aromatic halides

Condensation of an activated aromatic halide witli eitlier an alkali metal tliio-phenoxide or an alkali metal sulfide is performed under the same experimental condensations as used for polyetherification (Scheme 6.33).248... 

SNAr substitutions of activated aromatic halides, especially aromatic fluorides, provide useful means for the construction of aromatic diethers or amines. Primary and secondary amines react with l, 2-dihalo-4,5-dinitrobenzene to give nitro group substitution at room temperature. The halogen substituents on the ring remain unsubstituted and can be used in further transformation (Eq. 9.5).8... 

K18F has been used to prepare 18F-labeIled aromatic fluorides by nucleophilic substitution on activated aromatic halides.88,90... 

Polymers such as polyetherketones and polyethersulfones can be prepared by electrophilic aromatic substitution using aromatic acid chlorides and aromatic sulfonyl chlorides, respectively [Eq. (25)]. However, due to ortho-substitution in addition to the desired para-substitution, it is difficult for these Friedel-Crafts acylations to compete with nucleophilic aromatic substitution of activated aromatic halides which are usually used for their synthesis. 

Activated aromatic halides and 2- or 4-pyridyl halides can be used for the N-arylation of 1,2,4-triazoles, best achieved by the Ullmann technique (70JCS(C)8s). Preference for annular arylation on N-1 rather than N-4 is observed but arylations of 3-aminotriazoles with picryl chloride are anomalous the parent triazole itself is substituted on N-1 but in... 

Quite similarly, superoxide may react with some activated aromatic halides to give, through substitution, the corresponding phenols [262,263]. A consequence of the results and reactions described earlier is that for electrolyses conducted in aprotic solutions, adventitious oxygen may quite often cause large discrepancies, not only in coulometric... 

N,N-Dimethylarylamines. Activated aromatic halides undergo nucleophilic substitution with DMF (in the presence of ethanolamines). 

Etherification. Ethers of amyl alcohols have been prepared by reaction with benzhydrol (63), activated aromatic halides (64), dehydration-addition reactions (65), addition to olefins (66—71), alkoxylation with olefin oxides (72,73) and displacement reactions involving their alkali... 

TYPE OF POLYMERIZATION Nucleophilic displacement of activated aromatic halides in polar solvents by cilkali metal phenates or Friedel-Crafts processes examples include polycondensation of the potassium salt of hydroquinone and 4,4 -difluorobenzophenone in DMSO at temperatures up to 340°C and the polycondensation of 4,4 -difluorobenzophenone and silylated hydroquinone at 220-320°C. 

TYPE OF POLYMERIZATION NucleophUic displacement of activated aromatic halides in polar solvents by alkali metal phenates or Friedel-Crafts processes. 

Arylation of enamines with activated aromatic halides (128) is possible. It is of interest to note, however, that less reactive (harder) aryl halides could effect substitution at the nitrogen of enamines. 

In 1967, condensation polymerizations of alkali bisphenates with negatively substituted aromatic dihalides has been reported as part of a general study on the synthesis of polysulfones and polyethers (8). In the reaction, ether bonds are formed through the nucleophilic substitution of the aromatic dihalides. This reaction is fast and relatively free of side reactions in comparison with the Friedel-Crafts process. Figure 3.1 demonstrates this condensation reaction. In general, sodium or potassium bisphenates and difluoride substituted aromatic monomers were used. The dilithium, calcium, or magnesium salts are insoluble in DMSO and therefore cannot be used. The reported order of reactivity in activated aromatic halides is usually F Cl Br I or F Cl > Br > I. The difluorides are found to be more reactive than the corresponding dichlorides. 

At present, many sulfonated derivatives of polymers such as poly(ether ether ketone), polysulfone, poly (ary lene ether snlfone), poly(styrene), and polyCphenylene sulfide) have been developed for fnel cells [10-14], More recently, the synthesis of sulfonated poly(arylene ether snlfone) and/or snlfonated poly(arylene ether ketone)s copolymers by direct copolymerization of biphenol, disnlfonated-activated aromatic halide monomers, and the precnrsor—activated aromatic halide monomer for fnel cell membrane applications— were carried ont [12,15],... 

Friedel-Crafts acylation usually involves the reaction of an acyl halide, a Lewis acid catalyst, and the aromatic substrate. Several species may function as the active electrophile, depending on the reactivity of the aromatic compound. For activated aromatics, the electrophile can be a discrete positively charged acylium ion or the complex formed... 

Kinetic studies have shown that the enolate and phosphorus nucleophiles all react at about the same rate. This suggests that the only step directly involving the nucleophile (step 2 of the propagation sequence) occurs at essentially the diffusion-controlled rate so that there is little selectivity among the individual nucleophiles. The synthetic potential of the reaction lies in the fact that other substituents which activate the halide to substitution are not required in this reaction, in contrast to aromatic nucleophilic substitution which proceeds by an addition-elimination mechanism (see Seetion 10.5). 

The activation energy of substitution of an unactivated aromatic halide (e.g., fiuorobenzene and 2-chloronaphthalene ) is over 30 kcal while that of activated compounds is 5-20 kcal. For the tabulated reactions (Tables II-VIII) with alkoxide and with primary, secondary, or tertiary amines, resonance activation (cf. 278 and 279) by ortho or para nitrogens is found to be greater than inductive activation (cf. 251). This relation is qualitatively demonstrated in... 

The Ullman reaction has long been known as a method for the synthesis of aromatic ethers by the reaction of a phenol with an aromatic halide in the presence of a copper compound as a catalyst. It is a variation on the nucleophilic substitution reaction since a phenolic salt reacts with the halide. Nonactivated aromatic halides can be used in the synthesis of poly(arylene edier)s, dius providing a way of obtaining structures not available by the conventional nucleophilic route. The ease of halogen displacement was found to be the reverse of that observed for activated nucleophilic substitution reaction, that is, I > Br > Cl F. The polymerizations are conducted in benzophenone with a cuprous chloride-pyridine complex as a catalyst. Bromine compounds are the favored reactants.53,124 127 Poly(arylene ether)s have been prepared by Ullman coupling of bisphenols and... 

As noted in Section 11.2.2, nucleophilic substitution of aromatic halides lacking activating substituents is generally difficult. It has been known for a long time that the nucleophilic substitution of aromatic halides can be catalyzed by the presence of copper metal or copper salts.137 Synthetic procedures based on this observation are used to prepare aryl nitriles by reaction of aryl bromides with Cu(I)CN. The reactions are usually carried out at elevated temperature in DMF or a similar solvent. 

The first palladium-catalyzed formation of aryl alkyl ethers in an intermolecular fashion occurred between activated aryl halides and alkoxides (Equation (28)), and the first formation of vinyl ethers occurred between activated vinyl halides and tin alkoxides (Equation (29)). Reactions of activated chloro- and bromoarenes with NaO-Z-Bu to form /-butyl aryl ethers occurred in the presence of palladium and DPPF as catalyst,107 while reactions of activated aryl halides with alcohols that could undergo /3-hydrogen elimination occurred in the presence of palladium and BINAP as catalyst.110 Reactions of NaO-/-Bu with unactivated aryl halides gave only modest yields of ether when catalyzed by aromatic bisphosphines.110 Similar chemistry occurred in the presence of nickel catalysts. In fact, nickel catalysts produced higher yields of silyl aryl ethers than palladium catalysts.108 The formation of diaryl ethers from activated aryl halides in the presence of palladium catalysts bearing DPPF or a CF3-subsituted DPPF was also reported 109... 

Scheme 6.125 Nucleophilic aromatic substitutions of activated aryl halides.

We initiated our work by examining nucleophilic aromatic substitution, a somewhat difficult reaction to effect in other than activated aryl halides as substrates. It occurred to us that if polyhaloaromatics could be made to suffer disubstitution under mild solid-liquid PTC conditions, then they might be used as comonomers with a variety of bisnucliophiles to prepare halogenated polyaryl-ethers, sulfides, sulfone-ethers as well as other interesting polymers which are at present synthesized only with some difficulty. 

A continuous procedure for the alkylation of mesitylene and anisole with supercritical propene, or propan-2-ol in supercritical carbon dioxide, with a heterogeneous polysiloxane-supported solid acid Deloxan catalyst has been reported giving 100% selectivity for monoalkylation of mesitylene with 50% conversion at 250 °C and 150 bar by propan-2-ol in supercritical carbon dioxide. p-Toluenesulfonic acid monohydrate has been demonstrated as an efficient catalyst for the clean alkylation of aromatics using activated alkyl halides, alkenes or tosylates under mild conditions. Cyclohexene, for example, reacts with toluene to give 100% cyclohexyltoluenes (o m p-29 18 53) under these circumstances. 

Nucleophilic substitution of halogen atom in aromatic and heteroaromatic halides with a hydroxyamino group proceeds only in substrates that are activated by a strong electron-withdrawing substituent in the benzene ring (e.g. 27, equation 17). Despite this limitation this reaction is useful for synthesis of arylhydroxylamines and usually provides good yields of products. Along with activated aryl halides and sulfonates, activated methyl aryl ethers such as 28 can be used (equation 18). 

Tertiary and aromatic nitroso compounds react with aryl Grignard or aryl-lithium reagents giving the corresponding hydroxylamines . This reaction is useful for preparation of alkyl- and aiylhydroxylamines (e.g. 109, equation 80 and 110, equation 81) and can be considered as complementary to arylation of hydroxy lamines with activated aryl halides. It has been used for functionalization of cyclophanes with the hydroxy amino group. The main limitation of the reaction is the relatively restricted choice of available aliphatic nitroso components, so most of reactions were done with 2-nitroso-2-methylpropane. There is no literature data about the possibility of removal of the tert-butyl group from these compounds. 

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