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Recent developments1–3 in the synthesis of 4(1H)-pyridone derivatives have prompted us to communicate a highly versatile synthesis of this class of heterocycles. Acylation of the styrylamine (I)4 (R1 = C2H5) with a substituted arylacetyl halide (II) in ether at O[ddot]-30[ddot]C in the presence of triethylamine or pyridine gave in 2 to 24 hours the enaminoketone (III) (75%-85% trans-isomer together with 25%-15% cis-isomer based on chemical shift of CH methine proton). Enaminoketone (III) could be readily converted to (IIIa) with aqueous methylamine in ethanol or to the bis-enaminoketone (IV) with N,N-dimethylformamide dimethyl acetal. The enaminoketone (IIIa) could be cyclized to pyridone (V) by refluxing with N,N-dimethylformamide dimethyl acetal; alternatively, the bis-enaminoketone (IV) could be cyclized to pyridone (V) by overnight reflux with methylamine hydrochloride in ethanol. yields based on styrylamine were 30%-65%. These transformations are outlined in Scheme 1. As an example, the synt...

Uber die Struktur der roten Acylierungsprodukte von Pyridazinylhydrazonen Bei der Acylierung von Pyridazinylhydrazonen (3) mit Saurechloriden oder Anhydriden in Benzol entstehen scharlachrote Triazolo[4,3-b]pyridazine (4), deren Struktur durch Rontgenstrahlbeugungsanalyse gesichert wird.

The preceding communication reports on the synthesis of 3,5-diaryl-4(1H)-pyridone derivatives via enaminoketones derived from the acylation of styrylamines with substituted arylacetyl chlorides. In this paper we describe methods for the preparation of 4(1H)-pyridones bearing carboxylic acid, ester, nitrile, cycloalkyl, cycloalkenyl, and derived functional groups in the 3-position.

Cyclodehydrohalogenation by terminal N 1 -C 4 bond formation affords N-aryl-4-benzoyl-2-azetindinones from 3-benzoyl-3-bromopropionanilides in an unequivocal annelation process.

Two synthetic procedures have been developed for the preparation of azeto[1,2-a]quinoxaline- 1,3-diones, a novel class of fused heterocyclic β-lactams possessing a bridgehead nitrogen atom. Both processes are general and afford the title compounds in good yield. The infrared, proton magnetic resonance, and mass spectroscopic properties of the title compounds are discussed.

ω- (N-aryl-chloracetamido) -acetophenones have been cyclized with triethylamine in warm benzene solution to the corresponding 1,4-oxazines. The reaction appears to be general for any N-aryl substituent, as long as an overall electron-withdrawing substituent is present para- or meta, in the aromatic nucleus of the acetophenone moiety. The predominant tautomeric form present is shown by IR spectrography to be the “keto” tautomer in every case. The structure of one morpholine is confirmed by mass spectral fragmentation analysis.

Cyclodehydrohalogenation-beta-Lactams-Morpholin-3-ones-H'-NMR Spectroscopy N-Aryl-N-chloroacetyl-2-chlorophenacylamines (2) give morpholinones 3, or beta-lactams 4, depending upon the N-aryl-substituent. N-Phenyl-N- (2,3-dibromo-3-phenylpropionyl) -4-nitrophenacylamine did not undergo base-catalysed cyclization but gave, instead, the α,β-unsaturated, open-chain amide 5. N-Aryl-N-chloroacetyl-aminomethyl-2-naphthylketones afford only beta-lactams. The first attempt at the synthesis of a 2-chloro-3-oxo-morpholine resulted in the isolation of the 2-hydroxyderivative. The H1-NMR spectra of some more 3-oxo-morpholines have been recorded.

Aus der starken Aktivierung des Methinwasserstoffs in den Halogenacetaminomalonaten und -phenylacetaten 4 durch eine N-[4-Nitro-phenyl]-Gruppe bei der Cyclisierung zu den β-Lactamen 5 sowie der Lage der CO-Bande der Amidgruppe in 5 und der Ringbestandigkeit wird auf Coplanaritat des N-Nitrophenylrings mit den drei Valenzen des Stickstoffs in den Amiden 4 und Lactamen 5 geschlossen. In den N-[2-Chlor-4-nitro-phenyl]-und N-[2-Nitrophenyl]-halogenacetaminoestern 4h und i ist der Arylring aus der Ebene des sp2-Stickstoffs herausgedreht, begleitet von einer deutlichen Abnahme der Methinwasserstoff-Aktivierung.

The formation of a 2-oxo-azetidine from N-phenyl-N-chloroacetyl-4-fluoro-phenacylamine, and 3-oxo-morpholines from corresponding 4-bromo-derivatives 2 indicates the possibility of the existence of dπ-acceptor resonance between the aromatic ring and the bromo-substituent. H-NMR studies of some morpholines reported earlier 3 indicate a planar heterocyclic structure with a rapidly inverting N₋aryl substituent. Where the rotation of the N-aryl group is strongly hindered 16, the C2 methylene protons show a geminai coupling of -14.5 Hz4. The 2-oxo-azetidine (4) shows an ABX coupling pattern for its ring protons. Preliminary work attempting to extend the synthesis of morpholines to azepines has resulted instead in the formation of a pyrrolidone.

Two new derivatives of the 1,4-oxazine ring system (3a and 3b) derived from p-aminobenz-amides have been synthesized. The uv absorption spectra of sixteen representative 1,4-oxazines all show two high intensity bands (ϵ ∼ 105) between 220-400 ran. The positions and intensities of the absorption maxima have been correlated with the steric and electronic effects of the oxazine ring substituents.

The preparation and antimicrobial activity of a series of beta-lactams (3a-f) are described. These compounds were prepared from the 2+2 cycloaddition of beta,beta-disubstituted enamines with aryl isocyanates; compounds 3a-f underwent facile beta-lactam ring fission between aminal carbon atom C4 and the lactam nitrogen N1. The resisting formylacetanilide derivatives were devoid of antibiotic activity.

Potassium tertiary butoxide in dimethyl sulfoxide solution has been shown to act as an efficient base in effecting the cyclo-dehydrohalogenation of halogen-acylamino-esters and -ketones. For certain specific cyclizations it is superior to the bases thus far used, yielding compounds of high purity in short reaction times. The first reported synthesis of a piperidinone by this route has been achieved.

The preparation and antimicrobial activity of a series of beta-lactams (3a-f) are described. These compounds were prepared from the 2+2 cycloaddition of beta,beta-disubstituted enamines with aryl isocyanates; compounds 3a-f underwent facile beta-lactam ring fission between aminal carbon atom C4 and the lactam nitrogen N1. The resisting formylacetanilide derivatives were devoid of antibiotic activity.

Uber die Struktur der roten Acylierungsprodukte von Pyridazinylhydrazonen Bei der Acylierung von Pyridazinylhydrazonen (3) mit Saurechloriden oder Anhydriden in Benzol entstehen scharlachrote Triazolo[4,3-b]pyridazine (4), deren Struktur durch Rontgenstrahlbeugungsanalyse gesichert wird.