With Replacement of Halogen

Though the great majority of antiinflammatory agents contain some form of acidic proton, occasional compounds devoid of such a function do show that activity. Thus the nonacidic pyrazolylpyrimidine epi razole (47) is described as a nonsteroid antiinflammatory agent. Reaction of pyrimidinone 42 with phosphorus oxychloride leads to the chloro derivative Replacement of halogen with hydrazine gives... 

Aromatic amination by replacement of halogens with amines (example... 

The reaction of trifluoromethyl iodide with arene thiolates provides trifluoromethyl aryl sulfides via a single electron transfer (SET) reaction rather than the SN2 reaction, which is the only formal mechanism (Scheme 2.31). In general, perfluoroalkyl (Rf—X), ferf-alkyl, and vinyl and aromatic halides are strongly deactivated for the replacement of halogens with... 

A device that is also used in pyridine and purine chemistry is the initial replacement of halogen with a tertiary amine the resulting salt, now having a better leaving group, undergoes nucleophilic substitution... 

Figure 6.48 Intramolecular generation and application of an diazo[ Clacetate unit Replacement of Halogen with Phosphorus Nucleophiles...

The replacement of hydrogen with halogen takes place under thermal or photochemical conditions [J9, 20, 21] (equations 10-12). 

Replacement of hydrogen with halogen in fluoraarenes takes place by an ionic mechanism and is subject to the normal directing effects [27, 28, 29] (equations 13-15). 

Replacement of hydrogen with halogen can be carried out in the alpha position of fluorinated ethers, amines, aldehydes, or nitriles In 2,2,3,4,4,4 hexafluoro-bulyl methyl ether, chlorination occurs predominantly at the methyl, however, bromination occurs mostly at the internal position of the fluorobutyl group 133] (equation 20)... 

Table 8. Replacement of Hydrogen with Halogen in Benzotrifluoride...

Many reactions of fluorinated organics with metal halides result in the replacement of fluorine with halogen A general route to 1,1,1-trichloro- or tribromo-fluoroalkanes involves treating primary fluoroalkyl iodides with aluminum trichloride or aluminum tribromide [74], Benzylic [75, 76] or vinylic [72] fluorine can be exchanged for chlorine when treated with aluminum trichloride... 

Thus, reduction of the Mannich reaction product (65) from acetophenone leads to alcohol 66. Replacement of the hydroxyl group by chlorine (67) followed by displacement of halogen with the anion from o-cresol affords the ether 68. Removal of one of the methyl groups on nitrogen by means of the von Braun reaction or its modem equivalent (reaction with alkyl chloroformate followed by saponification) leads to racemic 69 which is then resolved with L-(+)-mandelic acid to give the levorotary antidepressant tomoxetine (69) [16]. 

With the exception of the reactions of trifluoromethyl radicals with sulfur vapor, which is really a separate class of reactions, if the power supplied to the load coil surrounding the reactor (see Fig. 2) was maintained at, or near, the minimum amount needed to support the discharge, in only two cases were compounds found that clearly resulted from reactions other than replacement of halogen by trifluoromethyl. The reaction of tellurium tetrabromide (or the chloride) gave, in addition to the products just reported, very small proportions of such species as BrCF2TeCF2Br and (C2F5)2Te, which were isolated in yields of... 

The recurring theme in work on corticoids discussed thus far with the exception of the 17-desoxy compounds consisted in the introduction of additional functions to the basic cortisone molecule. Some further success in producing biologically active molecules has been achieved by substituting unnatural functions for those present in the protoype molecule. Thus the hydroxyl groups at both C-ll and C-21 can be replaced by halogen with retention of activity. 

Similar results for the replacement of halogen on an olefinic linkage by phosphorus have been accomplished using dialkyl phosphites with palladium(O) catalysts.4179 Another reaction involving replacement of a vinylic halide by phosphorus utilizes palladium catalysis with a trimethylsilyl-substituted phosphine (Figure 6.19).80... 

Replacement of halogen in dimeric iminoboranes containing tetracoordin-ated boron is not so readily accomplished. For example, bis[(dichloromethyl-eneamino)dichloroborane]reacts with C4H9MgCl in nonetheric solvents to yield dimeric (dichloromethyleneamino)butylchloroborane, whereas C4H9Ii replaces both boron-bonded chlorine atoms by butyl groups 25). 

There are reasons to explain the catalytic activity of copper(ll) in terms of cation-radical mechanism. This mechanism is confirmed by the unusual direction of Meerwein reaction in some cases, for example, when the replacement of halogen by an aryl radical occurs in the reaction of halo-styrenes with aryldiazonium salts (Obushak et al. 1991). A cation-radical in the system [olefin-Cu(II)] has been detected by UV spectroscopy (Obushak et al. 1991). In the cases of cis isomers of benzylidenacetone (Allard and Levisalles 1972) and maleic esters (Isaev et al. 1972), the unreacted... 

Alkyl chlorides are with a few exceptions not reduced by mild catalytic hydrogenation over platinum [502], rhodium [40] and nickel [63], even in the presence of alkali. Metal hydrides and complex hydrides are used more successfully various lithium aluminum hydrides [506, 507], lithium copper hydrides [501], sodium borohydride [504, 505], and especially different tin hydrides (stannanes) [503,508,509,510] are the reagents of choice for selective replacement of halogen in the presence of other functional groups. In some cases the reduction is stereoselective. Both cis- and rrunj-9-chlorodecaIin, on reductions with triphenylstannane or dibutylstannane, gave predominantly trani-decalin [509]. 

---