Arylating agents

Aryl halide compounds such as fluorobenzene derivatives can be used to form covalent bonds with amine-containing molecules like proteins. The reactivity of aryl halides, however, is not totally specific for amines. Other nucleophiles such as thiol, imidazolyl, and phenolate groups of amino acid side chains also can react (Zahn and Meinhoffer, 1958). Conjugates formed with sulfhydryl groups are reversible by cleaving with an excess of thiol (Shaltiel, 1967). 

Fluorobenzene-type compounds have been used as functional groups in homobifunctional crosslinking agents (Chapter 4, Section 4). Their reaction with amines involves nucleophilic displacement of the fluorine atom with the amine derivative, creating a substituted aryl amine bond (Reaction 9). Detection reagents incorporating reactive aryl chemistry include 2,4-dinitrofluorobenzene and trinitrobenzenesulfonate (Eisen et al., 1953). These compounds form 

The amidine bond formed is quite stable at acid pH however, it is susceptible to hydrolysis and cleavage at high pH. A typical reaction condition for using imidate crosslinkers is a buffer system consisting of 0.2 M triethanolamine in 0.1 M sodium borate, pH 8.2. After conjugating two proteins with a bifunctional imidoester crosslinker, excess imidoester functional groups may be blocked with ethanolamine. 

N-substituted carbodiimides can react with carboxylic acids to form highly reactive, o-acylisourea derivatives that are extremely short-lived (Reaction 11). This active species then can react with a nucleophile such as a primary amine to form an amide bond (Reaction 12) 

Hydrazide-containing compounds also can be coupled to carboxylate groups using a carbodiimide-mediated reaction. Using bifunctional hydrazide reagents, carboxylates can be modified to possess terminal hydrazide groups able to conjugate with other carbonyl compounds (Chapter 4, Section 8). 

The imidoester (or imidate) functional group is one of the most specific acylating groups available for modifying primary amines. Unlike most other coupling chemistries, imidoesters posses minimal cross-reactivity toward other nucleophilic groups in 

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Quaternary bismuth compounds have not found extensive use ia industry or ia organic synthesis. In manifold studies of organobismuth(V) compounds as oxidi2ing and arylating agents, such quaternary bismuth compounds as (CgH )4Bi02CCH2, (CgH )4Bi02SCgH4CH2-4, and... 

Halogenated pyridazines are generally inert as arylating agents in Friedel-Crafts reactions. The only example is the reaction of 3,6-dichloropyridazine with resorcinol and hydroquinone to give 3-aryl-6-chloropyridazines. 

Dmitrofluorobenzene also serves as an arylation agent for a wide vanety of biologically useful amines including aromatic amines [5b], ammo acids [57], and ammocarbohydrates [55,59] Weak nucleophilic amines such as benzimidazole [60] and fluoroamines [61] can also be arylated (equation 30)... 

The mfluoromethyl group activates the fluorine in position 4 ofperfluorotolu ene toward reaction with carbon nucleophiles Examples on che use of perfluoro-toluene as an arylation agent abound, and in all cases, the 4-fluonne atom is replaced predommantly or exclusively [% 87,88,89, 90 (equation 48) In perjluoromesity-lene, the aromatic fluorine atoms are activated toward Ar reaction, and a reaction... 

All these transformations show that the arylbromides can exhibit a diversified reactivity as arylating agents by using metallic catalysts. 

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). 

Uson, R., Laguna, A., Fernandez, E.J., Mendia, A. and Jones, P.G. (1988) (Polyhalophenyl)silver(I) complexes as arylating agents crystal structure of [(p-2,4,6-C6F3H2)(AuPPh3)2]C104. 

The reaction has a broad scope and is currently being widely applied in fine chemicals manufacture. One limitation is that the arylating agent is largely limited to relatively expensive aryl bromides and iodides (see, however, Reetz et al, 1998), while the process... 

Arylcopper can be used as arylation agent to react with diorganotin dibromides, providing interesting aryl-substituted organotin bromides324 ... 

Hall-Petch relationship, 13 497 Haloacetic acids (HAAs), removal from drinking water, 17 806—807 Haloacetones, 1 163 Haloalkylating agents, 12 167 Haloalkylation, 12 166-168 Haloalkylbenzenes, intramolecular alkylation of, 12 169 IV-Halo-a-amino acids, 13 107 Haloaromatics, 13 573 Halobenzenes, as Friedel-Crafts arylating agents, 12 171 Halobismuthines, 4 28-29 Haloboration, 14 270 Halobrom (BCDMH,... 

Arenediazonium salts " - as well as arenesulphonylazo compounds have also found a use as arylating agents for arene tellurolates. 

Three main routes have been well established for the preparation of diorganyl ditellurides (1) The reaction of sodium ditelluride with alkylating or arylating agents. 

Palladium-catalyzed arylation of the electron-rich olefin bntyl vinyl ether has been accomplished in the ionic liquid l-butyl-3-methylimidazolium tetrafluoroborate using as the arylating agents aryl iodides and bromides instead of the commonly used, but commercially unavailable and expensive, aryl triflates. The reaction proceeds with high efficiency and remarkable regioselectivity, leading almost exclnsively to substitution by various aryl groups at the olefinic carbon a to the heteroatom of butyl vinyl ether (Xu et ak, 2001). 

Arylation of alkenes catalyzed by palladium compounds is known as the Heck reaction [65]. While these reactions are very sensitive to steric effects, subtle electronic contributions to the regiochemical outcome may be assessed by comparing reactions of alkenes with similar substitution patterns. The arylating agents, being the nucleophilic arylpalladium species, tend to dictate the facility of their reaction with unsym-metrical, electron-deficient alkenes. 

Table 14.16 Critical structural features which can affect the carcinogenicity of arylating agents.

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