178422-79-2Relevant articles and documents
Kinetic resolution of amines with enantiopure 3-N,N-diacylaminoquinazolin-4(3H)-ones
Al-Sehemi, Abdullah G.,Atkinson, Robert S.,Fawcett, John
, p. 257 - 274 (2007/10/03)
The title compounds (DAQs) are chiral when the two N-acyl groups are different because of the absence of rotation around the N-N bond (a chiral axis). Enantiopure DAQs have been obtained by incorporation of a chiral centre in enantiopure form either into the substituent at the Q2-position or into one of the N-acyl groups, or into both, followed by separation of diastereoisomers. This separation is unnecessary in one case because conversion of the N-monoacylaminoquinazolinone (MAQ) into the DAQ is completely diastereoselective. Neither is separation of diastereoisomers necessary with 3-[N,N-di-(S)-2-acetoxypropanoylamino]-2-diphenylmethylquinazolin-4(3H)-one 37a: this DAQ 37a has its N-N bond rendered a chiral axis by the bias in its imide moiety wholly in favour of one exo/endo conformation. The high chemoselectivity exhibited by N,N-diacetyl- or N,N-dibenzoylaminoquinazolinones in reaction with the less hindered of two secondary amines (pyrrolidine in the presence of 1 eq. of piperidine) has a stereoselective counterpart: reaction of the above enantiopure DAQs enantioselectively with racemic amines leading to kinetic resolution. Using 1 eq. of DAQ and 2 eq. of amine, both the derivatised and unreacted amine enantiomers are recovered with high enantiomeric excess (ee) (better than 90% ee in some cases). Some of the higher ees are found in the recovered amides where non-chemoselective attack on both N-acyl groups of the DAQ has occurred: from the opposite configurations of the amine component in the two amides and from the low enantiopurity of the recovered unreacted amine, reaction of each of the N-acyl groups with complementary enantiomers of the amine is occurring (parallel kinetic resolution). Although higher ees are, in general, obtained using secondary amines, high ees are obtained in some cases using 1-phenylethylamine and, in particular, amino acid esters (valine and alanine). The sense of enantioselectivity in the reactions of these DAQs with amines is controlled by the configuration of the N-N axis: replacing the Q group in an N-(S)-2-acetoxypropanoyl-N-acetyl-bearing DAQ by phthalimide, thus eliminating the N-N chiral axis, drastically reduces the level of kinetic resolution.
The N-N bond as a chiral axis: 3-diacylaminoquinazolinones as chiral acylating agents
Atkinson, Robert S.,Barker, Emma,Edwards, Paul J.,Thomson, Gordon A.
, p. 1047 - 1055 (2007/10/03)
3-Diacylaminoquinazolinones 10 and 15 have high enough barriers to rotation around their N-N bonds to allow separation of each into diastereoisomers. Interconversion of diastereoisomers 10a and 10b occurs on heating in boiling toluene and thermodynamic parameters for this process have been measured. The barriers to rotation around the N-N bonds in analogous monoacylaminoquinazolinones are not sufficient to permit isolation of stereoisomers at room temperature unless the exocyclic nitrogen is additionally substituted e.g. by an alkyl group as in 28. X-Ray crystal structure determinations carried out on 10a, 10b, 15a and 28b confirm the presence of chiral axes. Reaction of both diastereoisomers 15a and 15b with 1-phenylethylamine takes place with exclusive reaction at the 1-acetoxypropionyl carbonyl group and with partial kinetic resolution: the preferred sense of enantioselectivity obtained is dominated by the N-N axis.
