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Synthesis of 2(1H)‐quinoxalinone O‐(2′‐quinoxalinyl)oxime (3) results in two easily distinguishable crystal forms with different colours, providing a rare example of colour polymorphism. The crystal structures of the two forms have been determined and compared. Intermolecular interactions and light‐absorption characteristics of the polymorphs have been analysed by a mixed quantum chemical/molecular mechanical method. In one of the polymorphic forms the crystal field stabilises relatively high energy conformations by enhanced electrostatic interactions. The difference in the light absorption is found to be caused partly by a conformational difference of the molecules. The crystal field increases the difference in the absorption wavelengths and shift them towards higher values.

A facile convergent total synthesis of the selective, potent, and orally active V 2 nonpeptide antagonist, SR-121463, was developed by modification of the discovery route. One of the late intermediates, the sulfonyl chloride 1, was synthesized from 3-hydroxybenzoic acid (19) by regioselective sulfonation, O-methylation and amidation in four steps. Another late intermediate, indolin-2-one 2, was prepared from p-phenetidine (8) through the indolin-2-one 16, where the cyclohexanone moiety of 27 was introduced into the active 3-methylene group of 16 by sequential transformation using methyl acrylate and KOtBu. After formation of the cyclic ketal moiety of 13, its ring-opening was achieved by using NaBH 4 in the presence of CCl 3 COOH. The morpholino group in 2 was introduced in accordance with the discovery approach, starting from the 2-hydroxyethoxy derivative 14 through the tosyloxy derivative 15 with morpholine in a one-pot reaction. In this way, the indolin-2-one 2 was synthesized from 8 in six steps. Finally, acylation of the indolin-2-one 2 was achieved with the sulfonyl chloride 1 in the presence of KOtBu in dimethyl sulfoxide (DMSO) at room temperature. This synthetic route proved to be applicable for the large-scale synthesis of SR-121463.

Azodicarbonsaure-athylester (4) dehydriert 2-(Hydroxyimino)-l,2,3,4-tetrahydrochinoxalin (1) zu 2-(Hydroxyimino)-l,2-dihydro-chinoxalin (2), dessen Struktur durch Vergleichssynthese aus 2-Aminochinoxalin (3) bewiesen wurde. Die Umwandlung 1 + . 2 sollte iiber eine direkte Dehydrierung der Azomethin-Bindung laufen, da die Oxidation der Amidoximgruppierung ~ wie bei der analogen Bildung von 8 aus 7 gezeigt wird -auszuschlieBen ist. Weitere Dehydrierung von 2 mit 4 fiihrt -als erstes Beispiel einer zweistufigen Oxidation mit diesem Reagenz -zur Azoxyverbindung 9. Verbindung 9 bildet sich auch durch Kondensation von 2 mit 2-Nitrosochinoxalin (10). Im Gegensatz zu 2, liefert 1 mit 10 in einem intermolekularen RedoxprozeB die Verbindung 2. Amidoximes, 111. -Synthesis and Oxidation of 2-(Hydroxyimino)-l,2-dihydroquinoxalineDehydrogenation of 2-(hydroxyimino)-l,2,3,4-tetrahydroquinoxaline (1) withe thy1 azodicarboxylate (4) gives 2-(hydroxyimino)-1,2-dihydroquinoxaline (2), whose structure has been proved by its preparation from 2-aminoquinoxaline (3). Transformation 1 +2 can be regarded as a direct dehydrogenation of the azomethine bond; oxidation of the amidoxime moiety can be ruled out, as was also the case with the analogous formation of 8 from7. Further dehydrogenation of 2 with 4 gives the azoxy compound 9. This is the first example of a two-stage oxidation with 4. Compound 9 is also formed by condensation of 2 with 2-nitrosoquinoxaline (10). In contrast to 2, 1 reacts with 10 to give 2 by an intermolecular redox process.In einer fruheren Mitteilung2) berichteten wir uber die Synthese des 2-(Hydroxyimino)-1,2,3,4-tetrahydro-chinoxalins (l), das durch Edelmetallkatalysatoren nicht zum 2-(Hydroxyimino)-l,2-dihydrochinoxalin (2) aromatisiert werden konnte I), da die von den Atomen C-3 und N-4 abgespaltenen Wasserstoffatome die Hydrogenolyse der N -0-Bindung bewirkten. Dieser ProzeB ergab 2-Aminochinoxalin (3).In dieser Veroffentlichung beschreiben wir die Synthese und oxidative Umwandlung (Dehydrierung) von 2. *) Korrespondenz bitte an diesen Autor richten.

In basic media 0-Benzoyl-and 0-acetyl-2-benzylaminobenzamide oxime (Sb,c) give 5-substituted 3-(2-benzylaminophenyl)-1,2,4-oxadiazoles (9a, b), while on heating in pure water 2-amino-1-benzylbenzimidazole (10) is formed. Reaction of 2dN-acylbenzy1amino)benzonitrile (12) with hydroxylamine, or treatment of O-acyl-2-(N-benzoylbenzylamino)benzamide oximes (Sf, g) with acid give the novel 1,2-disubstituted 4(iH)-quinazolone oximes 13, which isomerize on heating with alkali by an ANRORC mechanism to the 1,2,4+xadiazoIes 9a,b.Recently, we reported the transformation of 3-(l-aminopropyl)-l,2,4-oxadiazoles (1) to a-acylaminopropionamide oximes (3). As an intermediate the cyclic amide oxime 2 was postulated (Scheme I)'). 3In this paper we report a ring transformation of similar character but of opposite direction, i. e. the conversion of 2 to 1 involving the formation of an aminooxadiazole 9 from a cyclic amide oxime 13.It was also recently reported by us that the monoacyl derivatives 4 and 5 of 2-aminobenzamide oxime are transformed, depending on pH, to various heterocycles, among others in acidic media to quinazoline-3-oxides2). We assumed that the latter are formed by an electrocyclic reaction from the benzoxdiazepin intermediate 6 which -in turnare produced from 4 or 5 by loss of water. Regarding the whole process, an important role can be attributed to the possibility that the N(l) = C(2) bond can be formed from the aromatic amino group (Scheme 2).Neither reaction 4 -+ 7 nor pathways involving 6 as an intermediate are in accord with concepts put forward in the literature concerning the formation of 7 and the related quinazoline-3-oxides ' ). 5 COPhIn order to clarify this situation we intended to prepare 2-benzylaminobenzamide oxime (8a) and its 0-and N-acyl derivatives 8b-e and study their ring closure. In these compounds the formation of the C(l)=N(2) bond from the aromatic amino group is precluded and therefore, according Chem. Ber.