Aryl dichlorides

Aryl halides are often susceptible to photochemical degradation. As described in Chapter 10 later in this book, cleavage of the C-X bond occurs with low quantum yield for aryl chlorides (132), higher quantum yields for aryl bromides and iodides (133), and high quantum yields for some aryl fluorides (e.g., fluoroquinolones) (134). Aryl chlorides are photolabile to homolytic and/or heterolytic dechlorination (43). For sertraline hydrochloride, decomposition of the aryl dichloride moiety occurs in solution when exposed to light (ultraviolet and fluorescent conditions). As shown in the following proposed mechanism, the major photochemical decomposition products include mono-chloro- and des-chloro-sertraline via homolytic cleavage (Fig. 91) (86). 

The practical advantages of the radical relay process over the use of a tethered arylio-dine dichloride reagent are several. First of all, an excess of the solution chlorinating agent can be used, so complete conversion of the substrate to product is achieved. Secondly, there is no need to premake an attached aryl dichloride by using CI2, so sensitive substrates can be used. Finally, other templates can be used that can capture and relay a chlorine atom but cannot themselves be converted to dichloride reagents. These will be described later. 

The first examples of the use of (NHC)-Pd complexes for the synthesis of poly (triarylamine)s by C-N coupling between a commercial aniline and dihalobi-phenyls were reported by Turner and Navarro using (NHC)-Pd complexes as precatalysts (Figure 4.33) [93]. The use of [(IPr)Pd(allyl)Cl] allowed for the synthesis of the desired polymer requiring a lower catalyst loading than that using the tri-terf-butylphosphine-based system previously reported [94]. The same authors later reported the unprecedented polymerization of aryl dichlorides with primary aryl amines [95]. 

HIGH MOLECULAR WEIGHT AROMATIC BIPHENYLENE POLYMERS BY NICKEL COUPLING OF ARYL DICHLORIDES... 

Properties of High Polymers Produced by the Copolymerization of 4,4 -Bis(p-Chlorophenoxy)diphenylsulfone and Aryl Dichlorides... 

Finally, the efficient Negishi coupling of unactivated aryl, heterocyclic, vinyl chlorides as well as aryl dichlorides catalyzed by binuclear and mononuclear NHC-Ni complexes was recently described by Chen and co-workers (Equation (10.18)). Elaborated heteroarene-functionalized NHC were found to be highly effective for the preparation biaryls and terphenyls in good to excellent yields under mild conditions. Notably, the binuclear nickel catalysts showed higher activities than mononuclear analogues, probably because of a bimetallic cooperative effect. 

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. 

This can be circumvented by choosing alkyl groups with no P H, eg, methyl, neopentyl, trimethylsilylmethyl, phenyl and other aryl groups, and benzyl. The linear transition state for -elimination can also be made stericaHy impossible. The most successful technique for stabilization combines both principles. The pentahaptocyclopentadienyl ring anion (Cp) has six TT-electrons available to share with titanium. Biscyclopentadienyltitanium dichloride... 

The addition of hydrogen fluoride to an aromatic isocyanide dichloride provides a route to the respective aryl-Af tnfluoromethyl amine [34] (equation 24)... 

The 1,5-isomers 13.3 (E = S) are colourless, air-stable solids. They are prepared by the cyclocondensation reaction of R2PN2(SiMe3)3 with sulfur dichloride or thionyl chloride. A similar cyclocondensation process, using a mixture of SeCU and Sc2Cl2 as a source of selenium, produces a mixture of the isomers 13.2 and 13.3 (E = Se, R = Ph). The structures of 13.3 (E = S, R = alkyl, aryl) are folded eight-membered rings with a cross-ring S S distance of ca. 2.50 This structural... 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

This method involves the direct polycondensation of aromatic diamines with aromatic diacids in the presence of an aryl phosphite (triphenyl phosphite) and an organic base like pyridine.7,9 70 71 The addition of salts improves die solubility of the polymer and, with this, the maximum attainable molecular weight.71 The concentrations are, however, lower than by the dichloride method. 

Aromatic compounds can also be arylated by aryllead tricarboxylates. Best yields ( 70-85%) are obtained when the substrate contains alkyl groups an electrophilic mechanism is likely. Phenols are phenylated ortho to the OH group (and enols are a phenylated) by triphenylbismuth dichloride or by certain other Bi(V) reagents. O-Phenylation is a possible side reaction. As with the aryllead tricarboxylate reactions, a free-radical mechanism is unlikely. ... 

Barton and coworkers have explored the arylation of various nucleophiles including nitroalkanes using bismuth reagents.105 Reaction of 2-nitropropane with triphenylbismuth carbonate gives 2-nitro-2-phenylpropane in 80% yield.106 Recently, this arylation has been used for the synthesis of unusual amino acids. Arylation of a-nitro esters with triphenylbismuth dichloride followed by reduction gives unique a-amino acids (Eq. 5.68).107... 

The reaction of 1-nitrocyclohexene with triphenylbismuth dichloride in the presence of triethylamine gives the deconjugated arylated product, as shown in Eq. 5.69.108... 

Treatment of (-)-ephedrine (42) with a variety of aIkyl(aryl)phosphonic dichlorides 106a-d afforded the isomeric pairs of the corresponding 2-alkyl(aryl)-2-oxo-l,3,2 oxazaphospholidines (Scheme 31 and Table 1) [32, 62-65],... 

Synthesis of 1,3,2 oxazaphospholidines 128a-c derived from (S)-prolinol 127 was based either on the thermal aminoalcoholysis of the latter with prochiral alkyl(aryl) phosphonousdiamides 51a-c or its condensation reaction with /-butylphosphonous dichloride carried out in the presence of triethylamine (Scheme 37) [68], The diastereomeric excesses of the prepared derivatives ranged from 80 to 95%. 

Reaction of the (S)-amino alcohol 171 with A-(2-bromoethyl)phosphoramidic dichloride or aryl phosphonodichloridates 154 in the presence of triethylamine led to the formation of a single diastereomer in each case of 1,3,2 oxazaphospholidine-2-ones 172a-e (taking into consideration that in the 31P-NMR spectra only one singlet in the range 6.49-2.45 ppm was observed) (Scheme 48) [79],... 

This is a very rare metal in cross-coupling reactions. Direct comparison of similar methylating reagents derived from Al, Ga, and In showed that the Ga derivative is the least reactive.165 Vinylgallium dichlorides underwent cross-coupling with aryl iodides in the presence of Pd catalysts with P(o-tol)3 the reaction is moderately tolerant to acidic functional groups.166... 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

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