In the compound of 2,4 dichloroquinazoline; if an amination reaction is done on 2,4 poitions, why is dioxane used as solvent? Why this solvent in particular (what are its properties, effect , and the difference from the other solvents to choose it than the others)? Also, why does the first amination work in cold conditions while the second amination requires hot temperature?
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To take you last question first - the first amination goes in easily because the pyrimindine ring is doubly activated with 2 electronegative groups (the 2 chlorines). Once one is replaced by an electron-donating amine the ring is no longer as activated so it requires more forcing conditions to displace the second chlorine. See here
Dioxan is a relatively high boiling solvent, quinazolines are readily soluble in it and is unreactive with amines
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$\begingroup$ can you please give me references for these answers to use? and why the first amination step was on cold while thes second on hot temperature? , and does dioxane have only this property among the other solvents ans i read it makes the amination reactions regioselective? $\endgroup$– NEMOCommented Jul 31 at 17:19
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1$\begingroup$ The temperature makes it regioselective not the solvent. $\endgroup$ Commented Jul 31 at 18:06
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$\begingroup$ okay i understood now thank you so much. Can you tell me why the first amination the under ice conditions the reaction was proceeded not the room temperature? and why the dioxane was also used in this cold conditions although there are other solvents that are more safe and can give the same effect as dioxane ? $\endgroup$– NEMOCommented Jul 31 at 18:45
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1$\begingroup$ Dioxane is one of a number of solvents you could choose. It boils at 101C and at that temperature the 2nd amination proceeds fast enough. It is also easily removed under reduced pressure using a standard lab rotary evaporator with water bath, not something you could say about DMSO or even DMF. As for why the first amination was run at ice bath temp rather than rt; that suggests it goes very vigorously and yo uwant the ice bath to contai e xotherm. $\endgroup$ Commented Jul 31 at 20:17
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1$\begingroup$ Cyclopentyl methyl ether is suggested as a greener alternative to dioxane sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/… $\endgroup$ Commented Aug 1 at 17:09