Quinazolinones, fluorinated

Pd(OCOCp3) in the presence of (5)-Syn-Phos (37) catalyses the asymmetric hydrogenation of dibenzothiazepines in CH2CI2 by H2 using 4-methoxybenzoic acid as the activator and that of fluorinated quinazolinones using THE as the activator to form eorresponding chiral dihydrodibenzothaizepines and fluorinated dihydroquinones, respectively, in excellent enantioselectivity and yield. 

Alkoxylation in the benzene ring of quinazolines and quinazolinones is readily achieved in the presence of an ortho-nitro group, and even in the absence of a nitro group, displacement of fluorine is still quite facile. Examples of haloquinazolines to have been alkoxylated include 5-chloro-8-nitro-4(3//)-quinazolinone 187 <2005BMC5613>, 7-chloro-6-nitro-4(377)-quinazolinone 188 <1996JME267>, 4-arylamino-7-fluoro-6-nitroquinazolines 189... 

In the case of 5,7-difluoro-4(377)-quinazolinone 194, selective displacement of the 5-fluorine was achieved at room temperature, and this was followed by displacement of the 7-fluorine by a different alcohol at reflux in THE <2005BML5446>. 

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