Trichloromethyl groups, nucleophilic displacement

Reaction of 5-trichloromethyl-1,2,4-thiadiazoles with secondary amines leads to amides. For example, treatment of (84) with piperidine gives (86) which presumably arises by nucleophilic displacement of chloride ion from the trichloromethyl group, followed by hydrolysis during work up of the resulting dichloro compound (85) (Scheme 21) <86PS(26)151>. 

The trichloromethyl group is said to be easier to displace with nucleophiles than chlorine itself when it is at C-5. This electron-withdrawing group enables one to demonstrate a difference in ease of displacement at C-5 with respect to C-3. Guanidine78, 176 will displace... 

Nucleophilic displacements. Trihalomethyl groups can be replaced in nucleophilic substitution reactions in sufficiently activated systems, as, for example, in r-triazincs. 2,4,6-Tris(trichloromethyl)-j-triazine is converted into 2,4,6-triamino-j--triazine by ammonia. 

Chloro-4,6-bis(trichloromethyl)-s-triazine (115) reacts with primary and secondary alkanols to displace only chlorine. Although stable to these acid-catalysis conditions, the trichloromethyl groups can be replaced stepwise, after chlorine, with sufficient alkoxide ion. With one mole of nucleophile, the chlorine was replaced by arylsul-fonylhydrazides, hydrazine, heterocyclic amines, hydroxylamine, thiocyanate, or triethylphosphite. Chlorine is also more reactive than pentafiuoroethyl and heptafluoropropyl groups on s-triazines. a,a-Dihaloalkyls have been little investigated. 

There are two possible condensation reactions for the nitrile. One is nucleophilic reaction of the oxyanion with the carbon of the nitrile functional group. This carbon is activated by nitrogen and by the strongly electron-withdrawing trichloromethyl group. The other possibility, 8 2 displacement of chloride, is ruled out because there are three chlorines and four bonds in the product. After the nucleophilic reaction, a trace of methanol is needed to form a neutral product by protonation of the anion. 

The displacement of nucleofugal groups is usually realized through the addition-elimination two-step mechanism Sn(AE) . For instance, the trichloromethyl group in 1,2,4-triazines is displaced easily by the action of hydrazine, butylamine, sodium hydroxide, and alkoxides (Scheme 81) <2004SOS(17)357> however, in the reaction of 6-aryl-3-trichloromethyl-l,2,4-triazines with aromatic C-nucleophiles, substitution of hydrogen takes place <2004RCB1295>. 

Potential energy surfaces for nucleophilic displacements at phosphorus in dimethyl methyl-, chloromethyl-, dichloromethyl-, and trichloromethyl-phosphonates were computed by DFT methods. The results revealed that sequential introduction of chlorine substituents at the methyl group of a methylphosphonate diester increased the stability of TSs and intermediates leading to P-C bond cleavage. Indeed, the trichlorinated analogue (23) reacted with NaOMe exclusively via P-C bond dissociation to form dichlorocarbene, which was trapped by various alkenes to form the corresponding gem-dichlorocyclopropanes (24) (Scheme... 

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