Stereochemical studies 136. saturated heterocycles 141.1 synthesis and conformational study of stereoisomeric 2,2-disubstituted-5,6-tri- and -5,6-tetramethylene-tetrahydro-1,3-oxazin-4-ones (original) (raw)

Stereochemical studies, 73. Saturated heterocycles, 60

Monatshefte Fur Chemie, 1985

N-Substituted-2-carboxamido-l-cycloalkanols were cyclized with 1,1'-carbonyldiimidazole to synthesize cis-and trans-N-alkyl-, N-aralkyl-and N-aryl-2,4dioxo tri-and tetramethyleneperhydro-l,3-oxazines. The structures of the compounds and their cis or trans ring anellation were confirmed by IR, 1H-and ~3C-NMR spectroscopy, and the cis and trans pairs of isomers were compared to establish the predominant conformation of the flexible cis isomers. It was found that-similarly to the 1,3-oxazin-2-and-4-ones studied earlier-the "O-endo" conformers are preferred, in which the 1-oxygen atom is axial to the alicyclic ring; this is independent of the number of ring atoms in the alicycle, and of the presence of an oxazinedione ring, even though this is more flexible that the ring of oxazinones.

Stereochemical studies—XXXVII: Saturated heterocycles—XIII Configuration and conformation ofZ- andE-N-methyl- and -N- benzyl-2-p-nitrophenyl-4,5- and -5,6-tetramethylenetetrahydro-1,3-oxazines

Organic magnetic resonance, 1980

The configuration and conformation of Z-and EN-methyl-and-N-benzyl-2-pnitropheayl-4,5-, and-5,6-tetramethylenetetrahydro-1,3-oxazines were determined by 'H and "C NMR spectroscopy. The Z isomers were proved to be conformationally homogeneous, having the heteroatom in axial and equatorial position, respectively, in the case of the 5,6-and 4,5-tetramethylene compounds. Consequently, the pnitrophenyl group and the anellated cyclohexyl ring are all-cis arranged in the Z-5,6-tetramethylene compounds while in the case of the Z-4,5-tetramethylene isomers the pnitrophenyl group and the cyclohexyl ring are trans arranged to the hetero ring.

Stereochemical studies 130 saturated heterocycles 132

Tetrahedron, 1987

Through condensation of cis-2-hydroxymethylcyclopentylamine (3) and cis-2-aminomethylcyclopentanol (!) with aromatic alde6ydes, tautomeric mixtures of 1,3-oxazifies and open-chain Schiff bases were obtained. The two series of compounds (4a-f, 6a-f) gave satisfactory linear correlations correspofi~ifig ~8 Iog K× = k~÷ + log Kx~w(k = 0.76 ±0.04 as shown earlier~). The ring form of the corresponding trans derivatives is present in a fairly low amount, because~he strain in the trans fusion of the cyclopentane and the sixmembered hetero ring. N-Methyl substitution makes the ring form in the latter compounds stable, resulting in oxazines ~ and 14.__ All the cyclizations in question occurred stereo-speci~ically. The ring-chain tautomerism of tetrahydro-l,3-oxazines and 1,3-oxazolidines is a 2-3 well-known process. The tautomerism of oxazolidines has been thoroughly investigated, since the ring formation is a disfavoured 5-endo-tri~ process according to the Baldwin rules, 4-8 but for the 1,3-oxazine series quantitative data on the 9 tautomeric ratios are available only for 3,4-dihydro-2H-1,3-benzoxazines.

Stereochemical studies, 142. Saturated heterocycles, 1481 One-pot synthesis of partially saturated tetracyclic benzoxazines; Scope and Limitations

Tetrahedron, 1988

The partly saturated 1,3-benzoxazino[3,4-a][3,l]benzoxazine (2) and 1,3_benzoxaeino[3,2-c][l,3]benzoxazines (gp-2) were prepared in one-pot syntheses from trans-2-hydroxymethylcyclohexylamine (2) and trans-2-aminomethylcyclohexanol (5) via ring-chain tautomEric mixtures. IH nmr spectroscopic cha<actF ization of the products Ga-q, including the assignment of the resulting diastereomers IS presented.

Synthesis and Biological Activity of Some 3-Aryl-3,4-dihydro-2H-benz[e]- 1,3-oxazines/6-bromo-3-aryl-3,4-dihydro-2H-benz[e]-1,3-oxazines

Asian Journal of Chemistry, 2013

Many important medicines, dyes, insecticides, etc., are found in the series of heterocyclic compounds, called oxazines 1 and thiazines 2. They are found mainly in the polycyclic divisions in which other rings, such as the benzene ring, are fused to the oxazines or thiazine ring. A considerable number of reports concerning 1,3-oxazine 3-5 derivatives which have undergone their greatest development in the last few years came in to the notice. This is due to partially the fact that these compounds show interesting pharmacological activity 6-11 and wide range of biological activity with uses as herbicides and agricultural microbiocides, as well as bactericide, fungicide, antidepressive, antiinflammatory and antitumor agents 12-15. Moreover 1,3-oxazine monomers were recently used to develop a new type of phenolic resin namely polybenzoxazines, by the ring openining polymerization on thermal curing 16,17. EXPERIMENTAL Salicyldehyde (spectrochem), sodium borohydride (spectrochem), aniline (CDH), 4-methyl aniline (Thomas Baker), 4-chloro aniline (CDH), 4-bromo aniline (spectrochem), 2-aminopyridine (spectrochem), 3-aminopyridine (spectrochem), 5bromo-salicyldehyde (spectrochem) were used as received. Solvents were purified by standard procedures. All reactions and workup were conducted under air, except when noted otherwise. TLC was performed on MERCK TLC Silica gel 60 F254 plates and visualized by iodine. Yields refer

Synthesis and reactivity of 2-dimethylamino-4-alkenyl-1, 3-oxazin-6-ones

Tetrahedron, 1989

The Vilsmeier-Haack reaction on 4-alkylideneisoxazolin+ones gives 2-dimethylamino-4-alkenyl-l,3-oxazin-6-ones. Depending on substitution pattern, from these oxazinones, cr-pyrones, 2-pyridones and pyridines may be obtained. The results confirm the thermal equilibrium between 2-dialkylamino-1,3-oxazin-6-ones, iminoketenes and vinylisocyanates. We recently reported on the synthesis and reactivity of 2_dialkylamino-1,3-oxazin-6-ones', and now report the synthesis and reactivity of L-dimethylamino-4-alkenyl-1,3-oxazin-6-ones 2, heterocycles which we have obtained by a Vilsmeier-Haack type reaction from 4-alkylideneisoxazolin+ones 1. The starting isoxazolones la-h have been reported (see Table I) while compounds li,j were prepared according to known methods 2,3 (see Experimental). As is well known for isoxazol-5-ones4, the 4-alkylideneisoxarol-5-ones may exist in CH and NH tautomeric forms5. When the Vilsmeier-Haack reaction is carried out on 4-alkylideneisoxarol-5-ones la-j, the corresponding 2-dimethylamino-4-alkenyl-l,3-oxatin-6-ones 2a-j are readily obtained in good yields (Scheme I and Table I). The reaction path is analogous with that previously reported for the Vilsmeier-Haack reaction of isoxazol-5-ones'. On compound lg the reaction has been carried out in DMF solution (see Experimental). In this case, besides the oxazinone 29, the derivative 3 has been obtained. The structure of compound 3 was assigned on the basis of single-crystal X-ray diffraction analysis and Figure I shows the molecular shape and numbering scheme. 74x5 3 (15) CH2C12-MeOH (1OO:l) 171-172' lh3 Ph Ma COOU E-2h (51) CH2C12-Et20 (JO:11 122-123' 3 Z-2h (28) 116-117" lig Me Me COOEt E-21 (82) hexane-Et20 (3:l) oil 3 Z-21 (8) 64-65' ljg n-C3H7 Be COOMe E-23 (80) CH2C12-Et20 (3O:l) 74-75d 3 Z-23 (14) oil "Et20-hexane. bEt2O. 'CH2C12-Et20. dhexane. e This reaction has been carried out at 8O'C in DMF. 2-Dimethylamino-4-alkenyI-1,3-oxazin-6-ones E. M. BECCALLI et al. aldehydooxazinones E-6b,c (Table III). WPyrone 7e from E-6e A solution of the aldehydooxazinone E-6e (1 mmol) in CH2Cl2 (50 mL) was irradiated (Pyrex vessel) with a high pressure Hg lamp (Philips HPK 125W) for 30 min. The residue from the solvent evaporation was purified by column chromatography to give pure a-pyrone 7e (Table III). Pyridines 8b,c,e from aldehydooxazinones E-6b,c,e. General Procedure The aldehydooxazinone 6 (0.5 mmol) was dissolved in dioxane (15 mL), and then H20 (5 ml) was added. The reaction mixture was heated under reflux for 3h. The residue from the SOlVent evaporation was purified by column chromatography to give pure compounds Bb,c,e (Table IV). 2-Pyridones 9h-j by thermal reaction of oxazinones E-2h-j. General Procedure The oxazinone 2 (300 mg) was dissolved in anhydrous dioxane (5 mL) and the reaction was carried out in a sealed tube at 115°C for 72h. After solvent evaporation, the residue was crystallized (for the crystallization solvents see Table V) to give pure 9h (67%), 9i (64%) and 9j (57%). 2-Pyridones lOh-j by reaction with H20 of the oxazinone Z-2h-j. General Procedure The oxazinone 2 (200 mg) was dissolv:d in dioxane (4 mL) and then H20 (2 mL) was added. The reaction was carried out at 110°C for 15h in a sealed tube. After solvent evaporation, the residue was crystallized to give pure pyridones lOh-j (Table V). 2-Pyridones 9h-j and lOh-j by reaction with H,O of the oxazinones E-Eh-j. General Procedure The reactions were carried out as described above and after 15h at 110°C pure pyridones 9h-j and lOh-j were obtained after columnu chromatography (Table V). X-ray Structure Oetermination. All single crystal X-ray measurements were performed on a Nonius CAD-4 diffractometer. The used radiation was graphite monochramated MoKa, n=O.71069A. The structures were solved by direct methods (program MULTAN14). The refinements were made by minimizing the function C~~(lP,IP, l)2 with weights w=410/[02(10)+0.000412,]. Crystal data and some details of data COlleCtiOn and of full-matrix least-squares refinement are given in Table VII. (A) oxazinone 3 (XR-1). Single crystals of XR-1 suitable for X-ray difraction study were grown from methylene chloride. The compound co-crystallizes with the solvent and the crystal formula is C20H21N303.1/6CH2C12 with formula weight 365.6. The molecules, essentially by means of eleCtrOStatiC interactions involving the nitrogen atoms, the oxygen atom bonded to the oxatine ring and the carbon atoms of the dimethylimido group, make layers parallel to the c axis. Between couple of layers, around a 3 crystallographic point, a hole ,is formed that include solvent. Such a structure is quite stable a do not change by changing the Table VI. Spectral data of new compounds. Product IR (cm-') 'H-NMR(CDC13I 6. J(

Easy Access to New Heterocyclic Systems: 1,4-Oxazine and Substituted 1,4-Oxazines

The Journal of Organic Chemistry, 2007

Contents-Experimental details and characterization data: pages S1-S18-1 H and 13 C NMR spectra for compounds 1-10: pages S19-S51 S2 Experimental details THF was distilled from sodium/benzophenone ketyl immediately prior use. Dichloromethane was distilled over CaH 2 and methanol from magnesium turnings. The reactions were monitored by thin-layer chromatography (TLC) analysis using silica gel (60 F 254) plates. Compounds were visualized by UV irradiation and/or spraying with a solution of potassium permanganate, followed by charring at 150 °C. Column chromatography was performed on silica gel 60 (230-400 mesh, 0.040-0.063 mm). Melting points (mp [°C]) were taken on samples in open capillary tubes and are uncorrected. The infrared spectra of compounds were recorded on an Infrared Fourier Transform spectrophotometer using NaCl plates or KBr pellets. 1 H and 13 C NMR spectra were recorded on a spectrometer at 250 MHz (13 C, 62.9 MHz). Chemical shifts are given in parts per million from tetramethylsilane (TMS) as internal standard. Ionspray or electronic impact methodology were used to record mass spectra. Nomenclature of the obtained compounds follows the rules of IUPAC and was checked with AutoNom. 1 Petroleum ether (P.E.) had a boiling point range 40-60 °C. 4-(tert-butoxycarbonyl)-morpholine-3,5-dione (2). A solution of 3,5dioxomorpholine 1 2 (0.510 g, 4.43 mmol), di-tert-butyl dicarbonate (1.451 g, 6.65 mmol) and DMAP (0.054 g, 0.04 mmol) in acetonitrile (13 mL) was stirred at room temperature, under argon, for 1 h. After concentration, the residue was diluted in EtOAc. The organic phase was washed with brine, dried over anhydrous MgSO 4 and concentrated. The residue was diluted in a minimun of AcOEt. The addition of petroleum ether results in the formation of a precipitate, which is filtered through a filter paper. After concentration of the filtrate, a flash chromatography (petroleum ether:EtOAc, 7:3) afforded 2