Chloropyrimidines

Aryl and alkenyl phenyl sulfides are prepared by the reaction of aryl and alkenyl halides and inflates with tributylstannyl phenyl sulfide. 2-Chloropyrimidine (737) is used for the coupling[606,607]. The diaryl or divinyl sulfide 739 is prepared by the reaction of distannyl sulfide (738)[548], N,N-Diethylaminotributyltin (740) reacts with aryl halides to give arylamines[608]. 

A final method for the preparation of pyrido[2,3-carboxylic acid chlorides with enamines in the presence of base to give 6,7,8-trisubstituted 5-ones (253 254)... 

Better results were obtained when a mixture of chloroform and either pyrazole or C-methylpyrazoles was heated at 555 °C in a continuous-flow vapour phase reactor (79JCS(P1)2786). 2-Chloropyrimidines were obtained in high yields (51-89%). Indazole similarly gave only 2-chloroquinazoline (68%). 

Chloro-2,6-diaminopyrimidine (2,4-diamino-6-chloropyrimidine) [156-83-2] M 144.6, m 198 , 199-202 , pK 3.57. Purified by recrystn from boiling H2O (charcoal) as needles also crystallises from Me2CO. [Biittner Chem Ber 36 2232 1903 Roth J Am Chem Soc 72 1914 1950 UV J Chem Soc 3172 1962.]... 

The data show that in some cases basicity has a strong influence on reactivity. For example, the reaction of 2-chloropyridine derivatives with piperidine is about 3000 times as fast as that with pyridine the basicity change involved is in the order of 6 pA units. However, piperidine is only 4 times as reactive as morpholine with 2- or 4-chloropyrimidine as the substrate, although -dpAo in these cases is still fairly large, 2.5 units. Furthermore, even the qualitative correlation sometimes fails, and aniline is more reactive than pyridine in contrast to the expectations from their basicities. 

From the standpoint of geometrical considerations, the major difference is in the far greater steric requirements of the nitro group. This could result in either primary or secondary steric effects. Nevertheless, primary steric effects do not seem to be necessarily distinguishable by direct kinetic comparison. A classic example is the puzzling similarity of the activation parameters of 2-chloropyrimidine and 2,6-dinitrochlorobenzene (reaction with piperidine in ethanol), which has been described by Chapman and Rees as fortuitous. However, that nitro groups do cause (retarding) primary steric effects has been neatly shown at peri positions in the reaction with alkoxides (see Section IV,C, l,c). 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

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