2‐Amino‐2‐oxazolines, II: Reactivity of the Nitrogens. Crystal Structures of Two endo/exo N‐Substituted Compounds

Abstract

The amidine group of the five-membered heterocycle induces a tautomeric aminohmino equilibrium. In the 2-ami~2-0xazoline form the. endo nitrogen is more reactive than the exo one. In the ~1nho-2-oxazolidine form, the contrary occurs. Depending on the experimental conditions, substitutive reactions take place either on & endo or on the exo nitrogen. The crystal X-ray CtyStallOgraPhy.2-Amino-Zsxazoline, 2. Mitt.: Reaktivillt der N-Atome. Kristallstruktur von m e i endolcxo N-substihiedenverbindungen Die Amidin-Gruppe des 5-gliedrigen Heterocyclus bewirkt ein Amin-l Imindas exo-N. Im Imin-2-0xazolidin sind die Verhidtnisse umgekehrt. In Abhihgigkeit von den experimentellen Bedingungen wird entweder das endo-N oder das exo-N substituiert. Die Kristallstrukturen der zwei endo-/ex*Nsubstituierteh Verbindungen wurden bestimmt. sm-s of two~-~~b t i t~~ cmpounds were determined by Gleichgewicht. In der 2-Amino-2-oxazolin-Form iSt das endo-N RaktiVer ids 5 4 l-phenyl4piperazinyl)methyl2-amin0-2-oxazoline (COR 3224") is the most active compound of a series of 2-amino-2-oxazolines synthesized in our group'). Its antidepressant profile is close to that of vil~xazine~'~). 2-Amino-2-oxazoline differently substituted led to different biological activi ties4.').The amidine group of the five-membered heterocycle induces a tautomeric amino/imino equilibrium. It has been shown by X-ray crystallography that the amino form is preponderant in free bases whereas the imino form predominates in salts6).The two nitrogen atoms are nucleophilic centres allowing various substitutive reactions. Substitutive reactions with 2-amino-2-oxazolines take place either on the endo or the exo nitrogen atom, depending on the experimental condition^"^^).In the first part of this work we try to explain the different reactivities of these two nitrogens by calculating the reactivity indices and the frontier orbital charge distribution of the two limit forms of the 2-amino-Zoxazoline ring.In the second part, we describe the synthesis and the X-ray crystal structures of two COR 3224-like molecules substituted one on the endo, the other one on the exo nitrogen of the amino-Zoxazoline moiety. Results and Discussion Part I: Theoretical CalculationsAll calculations were performed with the Chem-X software package") using a PS 330 Evans and Sutherland graphic terminal.The coordinates sets for the amino/imino -2-oxazoli(di)ne moieties have been published6*' ').The partial atomic charges, net charges, expressed in electric charge units 25 and the n bond indexes were calculated using the CNDOL? program'*). For the calculation of the reactivity indices we used the HMO approximation in which for an atom p, the reactivity index is the electronic density in the limit orbital HOMO") %,HOMO = 2C2,,,HOM0 where C,, are the coefficients associated to the corresponding atomic orbitals in the HOMO. -Amino-;! -0xazolineThe geometry of this group was derived from the X-ray crystal structure of 5-[ 1-(2-pyrimidyl)-4-piperazinyl]methyl 2-amino-2-oxazoline6). The calculated IC bond in...

Cationic ring-opening polymerization of protected oxazolidine imines resulting in gradient copolymers of poly(2-oxazoline) and poly(urea)

“…It was already described in literature that the endo-nitrogen of 2-amino-2-oxazoline, which is mainly present in solution, 54 is more reactive as compared to the exo-nitrogen. 55 The reactivity was predicted by density functional theory (DFT) from the molecule's geometry derived by X-ray crystal analysis. Based on the π-bond lengths, the electronegativity of the atoms could be calculated (endo-nitrogen: −0.317, exo-nitrogen: −0.272), explaining the differences in reactivity.…”

Delocalized π‐electrons in 2‐oxazoline rings resulting in negatively charged nitrogen atoms: revealing the selectivity during the initiation of cationic ring‐opening polymerizations

“…The regioselectivity of the initiation, which occurs exclusively at the nitrogen atom even in the case of highly reactive cations, was investigated in this study. In the literature, previous investigations of π‐electron delocalization phenomena in 2‐oxazolines focused on heteroatom‐containing 2‐oxazolines like 2‐thioxo‐ and 2‐amino‐2‐oxazolines, where π‐electron delocalization could neither be separated from the involvement of the S and N heteroatoms nor attributed to the CNO segment itself 31–33. In the example of β‐keto oxazolines, which were crystallized as enaminones, π‐electron delocalization involving the CO bond was observed, but again could not be referred to the tautomeric 2‐oxazolines 34.…”