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To study the effect of radiation therapy on the structural and elemental composition of permanent teeth enamel in vitro.

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 Od`-30d`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[image omitted] example, the synthesis of 1-methyl-3-(4-nitrophenyl)-5-phenyl-4(1h)-pyridone (Va) is outlined. Addition of 4-nitrophenylacetyl cloride (0.08 mole) in chloroform (200 ml) to diethylstyrylamine5 (0.08 mole) in chloroform (400 ml) in the presence of triethylamine (0.09 mole, dried over KOH) over a period of 2 hr and under nitrogen atmosphere gave a reddish solution. After stirring an additional hour, the reaction was washed with 1N HC1, N/10 NaOH, and saturated aqueous NaC1, dried over MgSO4, and filtered through Darco-60G to afford on removal of solvent 8.8 g (32%) of the transenaminoketon6 as a crystalline solid from 2-propanol (III, R2 = 4-nitrophenyl, R1 = C2H5; vco 1655 cm-1; δ ppm, 0.97, t, 6H; 3.02, q, 4H; 3.55, s, 2H; 7.72, s, 1H; 7.0-8.1, m, 9H. Anal. Calcd. for C20H22N2O3, % C, 70.99; H, 6.55; N, 8.28. Found: C, 70.84; H, 6.42; N, 8.21 (mp 141°-142°). To 6.0 g of (III) g dissolved in 60 ml of methanol was added 12.0 g of methylamine hydrochloride, and the mixture was heated to reflux for 18 hr. Workup with chloroform gave a quantitative recovery of analytically pure compound (IIIa) as an oil (δ ppm 3.0, d, 3h; 3.53, s, 2H; 6.80, d, 1H; 7-8, m, 9H; Anal. Calcd. for C17H16N2O3, % C, 68.91; H. 5.44; N, 9.45. Found: C, 68.68; H, 5.24; N, 9.20). To 4.85 g of (IIIa) was added 2.14 g (1 equivalent of N,N-dimethylformamide dimethyl acetal and 20.0 ml of anhydrous DMF. The reaction mixture developed an intense blue-violet color which was discharged during refluxing for 16 hr. All volatile components were removed on a rotary evaporator at 80°C/8 Torr to giva a microcrystalline precipitate of the pyridone (Va), which was recrystallized from 2-propanol/DMF to give 3.3 g (66%) of (Va) as bright yellow needles. (vco 1652; δ ppm 3.86, s, 3H; 7.2-8.25, m, 11H; Anal. Calcd. for C18H14N2O3, % C, 70.58; H, 4.61; N, 9.15. Found: C, 70.79; H, 4.89; N, 8.86; mp 212°-214°).

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-beta-Lactams-Morpholin-3-ones-H'-NMR Spectroscopy

The formation of a 2-oxo-azetidine from N-phenyl-N-chloroacetyl-4-fluoro-phenacylamine, and 3-oxo-morpholines from corresponding 4-bromo-derivatives 2indicates 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 3indicate a planar heterocyclic structure with a rapidly inverting N₋aryl substituent. Where the rotation of the N-aryl group is strongly hindered 16, the C2methylene 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.

The new route to the synthesis of 3-oxo-1,4-oxazines 1has been extended. N-aryl-N-chloroacetyl-m-nitro-phenacyl amines afford either only oxazine, or beta-lactam or both depending on the nature of the N-aryl substituent. A set of rules indicates from which precursors beta-lactam, as against morpholine formation, may be expected.

Since the discovery11of the activating effect of the N- (p-Nitro-phenyl)-group on the methine hydrogen of halogenacetamino esters, it has been found that the p-Acetyl-phenyl and m-Nitro-phenyl groups exert a similar effect. It has been shown that the delocalisation of the N-non-bonded electrons across the orbitals of the N-Aryl substituent is the governing factor in the cyclisation of the above systems, and the effect of the bulk of the N-Aryl substituent is relegated to a minor position.

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.