U168014.pdf (4.46 MB)
Intramolecular reactions of 3-acetoxy-aminoquinazolin-4(3H)-ones with aromatic rings
thesisposted on 2014-12-15, 10:35 authored by Rawdah Q. Lamphon
It has been shown previously that the reactivity of QNHOAc compounds as aziridinating agents for less reactive double bonds is increased in the presence of trifluoracetic acid (TFA). Similarly (Chapter 2), reaction of the tethered aromatic ring with the acetoxyamino nitrogen occurred only in the presence of TFA in QNHOAc compounds with 4-methoxy-phenyl-ethyl or -propyl and phenoxy-methyl or -ethyl as the (Q)2-substituent. The major product in each case was that from ortho-substitution, formally by QNH, on the aromatic ring. In the absence of TFA only the corresponding 3H-quinazolinone (QH) was obtained. In three cases, with 2-chloro-, 2-bromo or 2,4-dibromophenoxymethyl as the QNHOAc 2-substituent, no reaction products resulting from attack on the aromatic ring were obtained even in the presence of TFA. It was surprising, therefore, that attack on the aromatic ring took place with 2,4-dichlorophenoxyethyl or 1-(2,4-dichlorophenoxy)ethyl as the (Q)2-substituent (in QNHOAcs 190 and 212, respectively) in the presence or absence of TFA. In the absence of TFA, the major products from 190 and 212 were analogous 4,6-dichloroazepines believed to arise by aziridination of the 1,6-double bond of the aromatic ring. In the presence of TFA, the major products are related but not analogous azepinones and either 2-(2-nitroso-4-chlorophenoxymethyl-3H-quinazolin-4(3H)-one (from 190 or the product from formal insertion into the ortho-carbon chlorine bond (from 212) all of which, it is suggested, are derived by aziridination of the 1,2-double bond of the 2,4-dichlorophenyl ring. Thus addition of TFA to the reaction medium brings about a change in the regioselectivity of the intramolecular aziridination. In Chapter 3, the synthesis and intramolecular reactions of a further seven QNHOAc compounds with a- or b-naphthoxymethyl as 2-substituents were examined as model compounds for the synthesis of enantiopure 1,2,3,4-substituted naphthalenes. In three cases the intermediate aziridines were isolated and in one of these cases the unreacted (styrenoid) double bond was further aziridinated intermolecularly. The QNHOAc compound having a 2-[1-(6-methoxy-a-naphthyl]ethyl] substituent, derived from (S)-Naproxen, under-went aziridination of the naphthalene 1,2-bond highly diastereoselectivity.
Date of award2002-01-01
Awarding institutionUniversity of Leicester