Activating groups, aromatic

Nucleophilic Displacement Reactions. The presence of activating groups, eg, o,p mX.1.0 groups, makes aromatic fluorine reactive in nucleophilic displacement reactions. This has been demonstrated by deterrnination of the relative fluorine—chlorine displacement ratios from the reaction of halonitroben2enes with sodium methoxide in methanol (137) F is displaced 200—300 times more readily than Cl. 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Resonance effects are the primary influence on orientation and reactivity in electrophilic substitution. The common activating groups in electrophilic aromatic substitution, in approximate order of decreasing effectiveness, are —NR2, —NHR, —NH2, —OH, —OR, —NO, —NHCOR, —OCOR, alkyls, —F, —Cl, —Br, —1, aryls, —CH2COOH, and —CH=CH—COOH. Activating groups are ortho- and para-directing. Mixtures of ortho- and para-isomers are frequently produced the exact proportions are usually a function of steric effects and reaction conditions. 

Bromine can replace sulfonic acid groups on aromatic rings that also contain activating groups. PhenoHc sulfonic acids, for example, are polybrominated (24). 

The carrier-active chemical is selected according to its effectiveness at various temperatures. Members of the phenoHc group (Table 2), considered to be stronger carriers, are employed for formulations to be used in open equipment at the boil. Weaker carriers, such as the members of the aromatic ester group, are utilized generally for high temperature dyeing. 

The exchange of aromatic protons can be effected in the absence of any -OH or —NH2 activating group during the course of a Clemmensen reduction in deuteriochloric and deuterioacetic acid mixture (see section Ill-D). This reaction has been carried out with various tricyclic diterpenes and is best illustrated by the conversion of dehydroabietic acid into its 12,14-d2-labeled analog (40 -+ 41).Amalgamated zinc is reportedly necessary for the exchange reaction since the results are less satisfactory when a zinc chloride-mercuric chloride mixture is used. 

The efficacy of ring fluorination depends on the nature and position of the activating group, Y, m the aromatic ring The relative extent of for N (CH3)3 displacement decreases in the following order for Y p-NOy (71%), p-CN (24%), P-CH3CO (15%), p CHO (<5%) = m NO2 (<5%) This fluorodequaternization technique was subsequently adapted to prepare numerous NC A (no-camer-added) F-labeled aryl fluorides [7J, 74]... 

Arenediazonium ions 1 can undergo a coupling reaction with electron-rich aromatic compounds 2 like aryl amines and phenols to yield azo compounds 3. The substitution reaction at the aromatic system 2 usually takes place para to the activating group probably for steric reasons. If the para position is already occupied by a substituent, the new substitution takes place ortho to the activating group. 

The isomer of isoproterenol in which both aromatic hydroxyl groups are situated meta to the side chain also exhibits bron-chiodilating activity. Oxidation of 3,5-dimethoxyacetophenone by means of selenium dioxide affords the glyoxal derivative (15). Treatment of the aldehyde with isopropylamine in the presence of... 

Replacement of the aromatic hydroxyl groups in isoproterenol by chlorine again causes a marked shift in biologic activity. 

Activity is apparently retained when the aromatic amino group is deleted. Brominadon of acid 148 followed by reaction of the product (149), as its acid chloride, with the (S)-(-)-amino-methylpyrrolidine 150, gives the dopamine antagonist, remoxipride (151) [37] with (S)-configu-ration. 

Activating group Hammett cr value Deshielding of aromatic proton value (5) Ref. 

Activating group (Section 16.4) An electron-donating group such as hydroxyl (-OH) or amino (— NH2) that increases the reactivity of an aromatic ring toward electrophilic aromatic substitution. 

Acifluorfen, synthesis of, 683 Acrolein, structure of, 697 Acrylic acid, pKa of, 756 structure of. 753 Activating group (aromatic substitution), 561 acidity and, 760 explanation of, 564-565 Activation energy, 158 magnitude of, 159 reaction rate and, 158-159 Active site (enzyme), 162-163 citrate synthase and, 1046 hexokinase and, 163... 

The most practical method for the preparation of polyfarylcnc ether)s employs nucleophilic aromatic substitution (SnAi). Although nucleophilic substitution can occur via four principal mechanisms,49 the most important mechanism utilized for the synthesis of poly(arylene etlier)s has been SnAt, in which activating groups are present on the aromatic ring (Scheme 6.10). 

Reduction of the aromatic amine (15) is the usual source of (14), and reductive amination of (16) gives (15). There are many published routes to (15) of which addition of an activating group (17) is probably easiest on a large scale. You may also have considered using nitro compound (18) or epoxide (19). 

As described in Section 7.4, hexamethyldisilane 857 reduces, analogously, pyridine, quinoline and isoquinoline N-oxides to the free bases [17] and converts aromatic nitro groups to azo compounds [12]. Likewise, as already discussed allyltti-methylsilane 82 and benzylttimethylsilane 83 will gradually dehydrate and activate BU4NF-2-3H20 in situ to catalyze the addition of 82 and 83 to pyridine, quinoline, and isoquinoline N-oxides [13] (cf Section 7.2). 

A kinetic study of the previously reported substitution of aromatic nitro groups by tervalent phosphorus has established an aromatic 5n2 mechanism. Similarities in values of activation energies, and in relative reactivities of phosphite and phosphonite esters, between this displacement and the Arbusov reaction suggest a related mechanism (31), while the lack of reactivity of p-dinitrobenzene is attributed to the need for intramolecular solvation (32). The exclusive formation of ethyl nitrite, rather than other isomers, is confirmed from the decomposition of triethoxy-(ethyl)phosphonium fluoroborate (33) in the presence of silver nitrite. A mechanism involving quinquevalent phosphorus (34) still seems applicable, particularly in view of the recent mechanistic work on the Arbusov reaction. ... 

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