Heterocycles from heterocycles. 1,3-Diaryl-4,5-imidazolidinediones from 1,3,5-triarylhexahydro-1,3,5-triazines and oxalyl chloride (original) (raw)

Synthesis of symmetrical N-tosyldiazamacrocycles and complexation properties of their derivatives

Journal of Inclusion Phenomena, 1987

cipitate more solid. The solid was recrystallized from water to give 23 as a white crystalline solid (8.3 g, 66%): 'H NMR (DMSO&) 6 9.03 (t, J = 2 Hz, 1 H), 8.83 (d, J = 3 Hz, 1 H), 8.12 (m, 1 H); ' q NMR (DMSO-de) 6 126.8 (dd, J = 8, 2 Hz); IR (KBr) 3067 (s), 2462 (br), 1713 (s) cm-'; MS, m l e 141 (M').

Chem. Heterocyclic Compds. 1998, 34, 69-72

Intramolecular cycloaddition of alkenes to nitrons is an efficient method of constructing hinged bridge systems [1][2][3][4]. Due to the high regio-and stereospecificity of formation of adducts and ease of transformation of their isoxazolidine fragment, this reaction was used in synthesis of complex structures, for example, the alkaloid luciduline [5], prostaglandins [6], secoishvaranol-12 sesquiterpene [3], and ambrosin [7].

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(

Stereochemical studies 83 saturated heterocycles 76

Tetrahedron, 1985

The cls-In earlier papers ne reported the conversions of a-and trenr-2-(amlnomethyl)-1-cyclohexenol, Gand trene-2-(hydroxymethyl)-I-cyclohexylamine, and their homologuss containing cyclopentane, fused-skeleton dlhydro-2 cycloheptatae and cyclooctsne ekelstons. to and tat rehydro-1.3-oxuinee 1,3-oxazlne-2-thlones476, 3. 1,3-oxazln-2-ones and G. BERNATH et al. t9traa9thy19n9-1,3-oxazins snd analoguss with unsubstitutsd nitrogen which wars prepared from 2-(hydroxywthyl)-l-cycloh9xylanin9. whereas the ~substitutsd dsrivativss of a-1,3-oxazins and a-1,3-oxazin-2-one had the &-outside conformer as ths favoursd form', The predominant conformations dstsrainsd in solution wsrs confirmed in many cases by X-ray diffraction analysis (ass, 9-g. 10.11)* The present work is concerned with ths synthesis of fused-skeleton. blcyclic, partially saturated 3,1-b9ruoxazin99, 3,1-bsnzoxazin-2-ones and 3,1bsnroxstlns-2-thlonss containing an unsaturated cfrbocycls, and with the preparation of the related pyrlaidinonss. Systsaatlc H and 13C NMR studies and X-ray diffraction analyses were used to compars the conformstiona of the tstremsthylsns-1.5hstsrocyclss studied In detail sarllsr, and of the unsaturated analoguss reported in the present paper, Other objects of the present research ars the synthesis of biologically active compounds and study of the structure-activity relationship, Our sarlisr investigations showsd the u-trinsthylsne-condsnssd 1;3-hsterocyclse to bs more pharmacologically active than ths corresponding tstraa9thylsn9-condsnssd analogu9912, This suggsstsd the possible greater biological activity of the compounds in this ssrlss containing the cyclohsxsns structural unit. since this ring snsurss better coplanarity of the l olsculs than in the cyclohsxans analogu99, It is a special advantage that the starting material of the title compounds is the readily available e-1.2.3,6-tstrahydrophthalic anhydride, and the reactive double bond in the hstsrocycllc product9 affords wide possiblliti9s for further reactions, The starting &-2-amino-4-cyclohsxsns-1-carboxylic G. BERNATH t-1 al. For comparison with 1: and Ai, the octahydro analoguae ;?a and l,b ware also synthesized by the cycliration of cle cyclohexylamina13 _-and trana-2-(hydroxymethyl)-lwith pchlorobanraldehyde; the tie isomer &;a, similarly to 22, wee found to be unstable, The structure of &,3 was supported by X-ray diffraction analyeia"_ The aminoalcohols 5 and z were allowed to react with ethyl chloroformate to give the carbamatse I$ and && which were cyclired with sodium mathoxide to give uand trane-4a,5,8,8~tatrahydro-4H_-3,l-benzoxarin-2(1~)-onee rs and A? these carbon signals can also be observed in the case of ,8_ This is due to the steric compression ehif t*l causing increased shielding of carbon atoms to which stericelly hindered groups are attached, Finally, the dominant N-inside conformations are corroborated by the fact _that in the pairs 16-17 and 18-19 the field effect is greater for C-6 (5-O and 00 IP PI IP 4.5 ppm) than for C-5 (3-O ppm for both pairs); similarly, it is also larger for C-7 and C-8 than for the counterparts C-10 and C-9. This is explained by the position of the nitrogen atom better approaching the axial situation than Bern&h,