Pyrimidines deactivation effects

The deactivating effects of 2- and -amino groups in pyrimidine provide an interesting comparison. The 2-ethyleneimino group deactivates the 4- and 6-chlorines in 183 toward ethyleneimine in benzene at 50°, while the 4-ethyleneimino group in 184 deactivates the 6- but not the 2-chloro group. However, in contrast, 2-amino-... 

These pyridazines are subject to direct deactivation of the leaving group. It would appear from the conditions used in its reactions with ammonia (115°) and methylamine (50°) that 4-chloro-2-ethylthiopyrimidine (225) is somewhat deactivated (indirect). In various aminations of pyrimidines, the effect of an alkylthio group seems to be very mildly deactivating, like that of methyl groups. However, these surmises from the conditions used are not as reliable as the direct qualitative comparison described above and the kinetic data. 

The similarities in rate of nitration for the uracils suggest that they are all nitrated in the dioxo forms [log /r2(fb) at 40-50°C at H0 - 10.26 uracil, 1,3 1,3-dimethyluracil, 1.7 6-methyluracil, 1.9]. 2,4-Dimethoxypyrimid-ine is slower by a factor of 104. Whereas pyrimidin-2(l//)-one and its 1-methyl derivative also react as the free bases, the rates are much lower than those of the corresponding uracils [log /c2(fb) at 115°C at H0 -9.27 for pyrimidin-2(l//)-one is 8.1 for the 1-methyl derivative the value is 8.8], and 100 times slower than 3-methyl-2-pyridone. These results reflect the deactivating effect of a second annular nitrogen and the presence of only one oxo function [71JCS(B)1]. 

When going to more complex heterocyclic compounds—e.g., purines and pyrimidines, one sees that the effect of the —N=C < system is most pronounced and that all these compounds are highly reactive toward e aq (k > 1010 Af-1 sec.-1) (68). Like in the case of the carbonyl group the C=N— group is deactivated by electron donating groups bound to... 

The effect of activating and deactivating substituents is illustrated by the following 7,000-fold acceleration by a cyano group (Table VII, line 21) 2-5-fold deceleration by an alkyl group in chloropy-rimidines (Table III, lines 2 and 5-9) and in nitrochloropyridines (Table VII, lines 8 and 16) 12-18-fold acceleration by a 6-chloro group in 2,4-dichloro- vs. 2,4,6-trichloro-pyrimidine (Table V) cf. 

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