Chlorobenzene arylation

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253). The 1-bromo-1,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347[254], Enol tritlates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256] Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

Usually, iodides and bromides are used for the carbonylation, and chlorides are inert. I lowever, oxidative addition of aryl chlorides can be facilitated by use of bidcntatc phosphine, which forms a six-membered chelate structure and increa.scs (he electron density of Pd. For example, benzoate is prepared by the carbonylation of chlorobenzene using bis(diisopropylphosphino)propane (dippp) (456) as a ligand at 150 [308]. The use of tricyclohexylphosphine for the carbonylation of neat aryl chlorides in aqueous KOH under biphasic conditions is also recommended[309,310]. 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Chlorination is carried out m a manner similar to brommation and provides a ready route to chlorobenzene and related aryl chlorides Fluormation and lodmation of benzene and other arenes are rarely performed Fluorine is so reactive that its reaction with ben zene is difficult to control lodmation is very slow and has an unfavorable equilibrium constant Syntheses of aryl fluorides and aryl iodides are normally carried out by way of functional group transformations of arylammes these reactions will be described m Chapter 22... 

Because carbon is sp hybridized m chlorobenzene it is more electronegative than the sp hybridized carbon of chlorocyclohexane Consequently the withdrawal of electron density away from carbon by chlorine is less pronounced m aryl halides than m alkyl halides and the molecular dipole moment is smaller... 

Noticeably absent from Table 23 3 are nucleophilic substitutions We have so far seen no nucleophilic substitution reactions of aryl halides m this text Chlorobenzene for example is essentially inert to aqueous sodium hydroxide at room temperature Reac tion temperatures over 300°C are required for nucleophilic substitution to proceed at a reasonable rate... 

PMMA is not affected by most inorganic solutions, mineral oils, animal oils, low concentrations of alcohols paraffins, olefins, amines, alkyl monohahdes and ahphatic hydrocarbons and higher esters, ie, >10 carbon atoms. However, PMMA is attacked by lower esters, eg, ethyl acetate, isopropyl acetate aromatic hydrocarbons, eg, benzene, toluene, xylene phenols, eg, cresol, carboHc acid aryl hahdes, eg, chlorobenzene, bromobenzene ahphatic acids, eg, butyric acid, acetic acid alkyl polyhaHdes, eg, ethylene dichloride, methylene chloride high concentrations of alcohols, eg, methanol, ethanol 2-propanol and high concentrations of alkahes and oxidizing agents. 

It has been found that aryl groups can also be introduced into the a-position of sulphoxides. Corey and Chaykovsky have demonstrated that chlorobenzene reacts at room temperature with an excess of sodium methylsulphinyl carbanion to give methyl benzyl sulphoxide in 41% yield. The authors believe that a benzyne intermediate may be involved in the reaction400,401 (equation 174). 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

By comparison of the hydrolysis rate for the chloro- and bromobenzene catalyzed with cuprous oxide (Fig. 16), it is easy to show that the reactivity of bromobenzene as arylating agent is much higher than the reactivity of chlorobenzene the yields in phenolate is higher than 90 % after half an hour at 230 °C for the bromobenzene whereas the chlorobenzene affords only about 65 % after 15 hours, even at higher temperature (250°C). 

The use of imidazolium salts for in situ catalyst formation was shown to be optimal for the coupling of TMS-protected alkynes even with sterically demanding aryl bromides and avoids the formation of homocoupling-derived products. For this reaction, Nolan reported that the activation of chlorobenzene by this catalytic system was possible in moderate yield [125] (Scheme 6.41). 

Besides benzyl chloride, methyl- and/or chlorine-substituted benzyl chlorides, phenethyl chloride, etc. are also successfully employed to give 2 -diaralkylaminofluorans in excellent yield. However, aryl halides such as chlorobenzene and bromobenzene hardly enable the reaction, though aryl iodides such as iodobenzene give 2 -diarylaminofluorans in low yield. 

In general, symmetrical oxo-squaraines having the same end-groups are synthesized by reacting squaric acid with two equivalents of quatemized indolenine, 2-methyl-substituted benzothiazole, benzoselenazole, pyridine, quinoline [39, 45, 46] (Fig. 4) in a mixture of 1-butanol - toluene or 1-butanol - benzene with azeotropic removal of water in presence [39, 45] or absence [47] of quinoline as a catalyst. Other reported solvent systems include 1-butanol - pyridine [48], 1-propanol - chlorobenzene, or a mixture of acetic acid with pyridine and acetic anhydride [49]. Low CH-acidic, heterocyclic compounds such as quatemized aryl-azoles and benzoxazole do not react, and the corresponding oxo-squaraines cannot be obtained using this method [23, 50]. 

No mechanistic discussion was offered and the proposed conversion of 1,2,5-thiadiazole 156 into 1,2,4-thiadiazole 157 with MCPBA <1995J(P1)253> was incorrect, the error caused by incompletely purified 1,2,5-thiadiazole <1999JHC515>. In contrast, monohalogenated methyl aryl ketones gave 1,2,4-thiadiazoles 157 with tetrasulfur tetranitride in chlorobenzene at 110-115 °C <1992JHC1433>. 

The reactivity order Ni>Pd>Pt has been found for the oxidative addition of aryl halides. Steric and electronic properties, and the numbers of L as well as chelate effects, play an important role [65, 194—196]. For example, Pd(0) complexes of basic chelating phosphines react substantially more easily with chlorobenzenes than their nonchelating analogues (see Section 18.2.4) [2, 100, 196]. 

Recently, the groups of Fu and Buchwald have coupled aryl chlorides with arylboronic acids [34, 35]. The methodology may be amenable to large-scale synthesis because organic chlorides are less expensive and more readily available than other organic halides. Under conventional Suzuki conditions, chlorobenzene is virtually inert because of its reluctance to oxidatively add to Pd(0). However, in the presence of sterically hindered, electron-rich phosphine ligands [e.g., P(f-Bu)3 or tricyclohexylphosphine], enhanced reactivity is acquired presumably because the oxidative addition of an aryl chloride is more facile with a more electron-rich palladium complex. For... 

E)-stilbene was the exclusive product of the Pd colloid-catalyzed Heck arylation of styrene with chlorobenzene. Recently, a polymer-mediated self-assembly of functionalized Pd and Si02 nanoparticles have been found to be highly active catalysts for hydrogenation and Heck coupling... 

The Gomberg coupling reaction of aryl diazonium salts with arenes is catalysed by quaternary ammonium salts [49], Although yields are variable, they are generally >50% [49, 50]. When aromatic solvents other than benzene are used, the appropriate biaryls are produced, e.g. 4-chlorobenzenediazonium tetrafluoroborate reacts with chlorobenzene to produce the 2,4 -, 3,4 - and 4,4 -dichlorobiphenyls in a ca. 67 18 15 ratio. 

Sediment-solid and soil-solid samples can be treated in different ways prior to extraction depending on the purpose of the research program. Sediments or soils are stored more conveniently as dried powders. However, this technique is not appropriate if relatively volatile pollutants such as l-ring aryl hydrocarbons (e. g., alkylbenzenes, chlorohydrocarbons, chlorobenzenes), PAH (e.g., naphthalene) are to be determined. In such cases, the sediment or soil should remain frozen prior to analysis and extracted wet. 

In non-polar solvents many aminolysis reactions show a third-order dependence on the amine, B. This may be explained by catalysis of leaving-group departure by hydrogen-bonded homoconjugates, BH+B. Evidence for this pathway has been adduced from studies of the reactions of some nitro-activated (9-aryl oximes (7) with pyrrolidine in benzene, chlorobenzene, and dioxane, and with piperidine and hexylamine in cyclohexane. The third-order dependence on amine of the reaction of 2,6-dinitroanisole with butylamine in toluene and toluene-octanol mixtures has been interpreted in terms of a mechanism involving attack by dimers of the nucleophile. ... 

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