Ring transformations of 1,3-benzothiazine derivatives II conversion of 6α-aryl-7α-chloro-2,3(2′,3′-dialkqxybenzo)-1-thiaoctems3 into 2-carbomethoxy-3-aryl-7,8-dialkoxy-4.5-dihydro-1,4-benzothiazepines (original) (raw)

J. Am.Chem.Soc. 1988, 110, 3247-3252.pdf

Acid-catalyzed rearrangement of 6-bromo-2,4-dimethyl-4-(phenylamino)cyclohexa-1 ,4-dienone (1, a quinamine) in aqueous methanol gives, from a so-called quinamine rearrangement, 4'-amino-6-bromo-2,4-dimethyldiphenyl ether (2) and a number of byproducts. The ratio of yield of 2 to that of byproducts is 76:24. The byproducts are, mostly, 1,3-dimethylcarbazole (7) and some of its derivatives, the relative yields of which depend on the concentration of the catalyzing acid, HCI. The major byproduct in low HC1 concentrations is 1,3-dimethyl-4-methoxycarbazole (9). Kinetic isotope effects (KIE) were measured for the formation of 2 from 1, which was labeled at the carbonyl oxygen atom (['*0]-1), the nitrogen atom ([I5N]-1), and the para position of the aniline ring ([4-I4C]-1). The KIE (averages) were as follows: k ( ' 6 0 ) / k ( 1 8 0 ) , 1.0399; k(I4N)/k(l5N), 1.0089; /~( ' * c ) / k (~~C ) , 1.0501. The results suggest that the formation of 2 is a concerted process, a [5,5]-sigmatropic rearrangement, and not a two-step one, going through the rate-determining formation of a r-complex. KIE were measured for the formation of both 2 and 9 from 1, which was labeled in the ortho position of the anilino ring ([2-14C]-1). The KIE [k(12C)/k(14C)] were respectively 0.9895 and 1.0697. These results suggest that the byproduct (9) is formed by a concerted process, too, a [3,3]-sigmatropic rearrangement to an intermediate , which continues on to 9 and the other byproducts. The results show also that 2 cannot be formed from 1 by a succession of two [3,3]-sigmatropic rearrangements, the first of which is to 14. Thus, the quinamine rearrangements. on the basis of our results with 1, appear to be concerted, rather than a-complex intermediate, processes.

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,

11.Use of 0002www.iiste.org Call_for_Paper-Ethoxy(4H)-3,1-benzoxazin-4-one as a Precursor

The interactions of 2-ethoxy(4H)-3,1-benzoxazin-4-one (1) with various nitrogen nucleophiles such as ammonium acetate, hydrazine hydrate, ethanolamine, p-phenylenediamine, o-phenylenediamine, otolidine, dapsone, 2-aminophenol, 4-aminophenol, 4-aminobenzoic acid and 2-aminonicotinic acid have been discussed. The reactions of 2-thoxy-(3H)-quinazolin-4-one with ethyl chloroformate, phosphorus pentasulfide, chloroacetyl chloride and phosphorus oxychloride have also been investigated. Similar reactions of 2-ethoxy-4-chloroquinazoline with hydrazine hydrate and thiosemicarbazide have been introduced. Aminolysis of the 2-ethoxy group in some of the thiadiazoloquinazolinone derivatives has been attempted. The interactions of these aminolized derivatives and the 3-aminoquinazolinone with chloroacetyl chloride have been studied. All of the synthesized derivatives have been used in a wide range as starting materials for the synthesis of novel quinazoline and/or quinazolinones which have biological activity. The structures of all these products, obtained by heterocyclic ring opening and ring closure, were inferred by the IR, MS, 1 H NMR spectral as well as elemental analyses.

Russ. Chem. Rev. 2005, 74, 639-669

The published data on the intramolecular Diels ± Alder The published data on the intramolecular Diels ± Alder reaction in compounds of the 2-alkenylfuran series are general-reaction in compounds of the 2-alkenylfuran series are generalised. The methods and conditions for the preparation of tricyclic ised. The methods and conditions for the preparation of tricyclic systems are considered. The effects of the substituents in the furan systems are considered. The effects of the substituents in the furan and the unsaturated fragments on the cycloaddition are discussed. and the unsaturated fragments on the cycloaddition are discussed. The application of this reaction to the synthesis of alkaloids and The application of this reaction to the synthesis of alkaloids and terpenoids is exemplified. The bibliography includes 168 referen-terpenoids is exemplified. The bibliography includes 168 references ces. .

Russ. J. Org. Chem. 2010, 46, 1192-1206 (Zhurnal Organicheskoi Khimii, 2010, 46, 1191-1204)

Partly hydrogenated 2-[5-methyl(bromo, nitro)furan-2-yl]-substituted furo [3,2-c]quinolines, pyrano-[3,2-c]quinolines, and 4-ethoxyquinolines were synthesized by the imino Diels-Alder (Povarov) reaction. Cycloadditions of these compounds with maleic, citraconic, and dibromomaleic anhydrides, as well as with acryloyl, methacryloyl, and cinnamoyl chlorides led to the formation of substituted epoxyisoindolo[2,1-a]quinolines and -quinolinecarboxylic acids. Oxidation of the double C=C bond in the adducts, esterification of the carboxy group, and aromatization of the 7-oxabicycloheptene fragment were accomplished. s (3H, COMe), 2.97 d.d.q (1H, 3a-H, J 3a, 4 = 3.2, J 3a, 9b = 7.6, J 3a, 3 = 8.2 Hz), 3.74 d.t -H, 2 J = 3 J = 8.6 Hz), 3.82 q (1H, 2-H, 2 J = 8.4, 3 J = 4.4 Hz), 4.44 br.s (NH), 4.81 d (1H, 4-H, J 3a, 4 = 3.2 Hz), 5.22 d (1H, 9b-H, J 3a, 9b = 7.6 Hz), 6.30 d.d (1H, 3′-H, 4 J = 0.8, 3 J = 3.2 Hz), 6.38 d.d (1H, 4′-H, J 5′, 4′ = 1.8, J 4′, 3′ = 3.2 Hz), 6.59 d (1H, 6-H, J 6, 7 = 8.5 Hz), 7.40 d.d (1H, 5′-H, J 5′, 4′ = 1.8, J 5′, 3′ = 0.8 Hz), 7.74 d.d (1H, 7-H, J 7, 9 = 2.0, J 6, 7 = 8.5 Hz), 7.97 d (1H, 9-H, J 7, 9 = 2.0 Hz). Mass spectrum, m/z (I rel , %): 283 (100) [M] + , 268 (22), 254 (13), 238 (90), 210 (9), 198 (6), 172 (15), 167 (5), 103 (5), 81 (6), 43 (7). Found, %: C 72.31; H 6.21; N 4.78. C 17 H 17 NO 3 . Calculated, %: C 72.07; H 6.05; N 4.94. M 283.12. 1-H), 2.05 m (1H, 1-H), 2.34 d.d.d (1H, exo-10-H, J 9a, exo-10 = 3.9, J exo-10, 11 = 4.8, 2 J = 12.1 Hz), 2.76 d.d (1H, 9a-H, J 9a, exo-10 = 3.9, J 9a, endo-10 = 9.2 Hz), 3.21 m (1H, 13c-H), 3.89-4.03 m (2H, 2-H), 4.47 d (1H, 13b-H, J 13b, 13c = 3.4 Hz), 5.17 d.d (1H, 11-H, J exo-10, 11 = 4.8, J 11, 12 = 1.5 Hz), 5.37 d (1H, 3a-H, J 3a, 13c = 8.2 Hz), 6.47 d.d (1H, 12-H, J 11, 12 = 1.5, J 12, 13 = 5.8 Hz), 6.57 d (1H, 13-H, J 12, 13 = 5.8 Hz), 6.98 d.d (1H, 6-H, J 5, 6 = 7.7, J 4, 6 = 1.5 Hz), 7.21 t (1H, 5-H, J 4, 5 = J 5, 6 = 7.7 Hz), 7.22 d.d (1H, 4-H, J 4, 5 = 7.7, J 4, 6 = 1.5 Hz), 9.45 s (OH); cis isomer: 1.77 d.d (1H, endo-10-H, J 9a, endo-10 = 9.2, 2 J = 11.6 Hz), 1.90 m (1H, 1-H), 2.13 m (1H, 1-H), 2.17 d.d.d (1H, exo-10-H, J 9a, exo-10 = 3.9, J exo-10, 11 = 4.4, 2 J = 11.6 Hz), 2.55 d.d (1H, 9a-H, J 9a, exo-10 = 3.9, J 9a, endo-10 = 9.2 Hz), 3.15 m (1H, 13c-H), 3.89-4.03 m (2H, 2-H), 4.52 d (1H, 13b-H, J 13b, 13c = 2.9 Hz), 5.14 d.d (1H, 11-H, J exo-10, 11 = 4.4, J 11, 12 = 1.5 Hz), 5.35 d (1H, 3a-H, J 3a,13c = 8.2 Hz), 6.53 d.d (1H, 12-H, J 11, 12 = 1.5, J 12, 13 = 5.8 Hz), 6.58 d (1H, 13-H, J 12, 13 = 5.8 Hz), 7.00 d.d (1H, 6-H, J 5, 6 = 7.7, J 4, 6 = 1.5 Hz), 7.29 t (1H, 5-H, J 4, 5 = J 5, 6 = 7.7 Hz), 7.36 d.d (1H, 4-H, J 4, 5 = 7.7, J 4, 6 = 1.5 Hz), 9.45 s (OH). Mass spectrum, m/z (I rel , %): 311 (31) [M] + , ,13b,13c-hexahydro-3aH-furo[3,2-c]isoindolo[2,1-a]quinolin-9(9aH)-one (VIIId) (mixture of trans and cis isomers at a ratio of 1 : 1. Yield 87%, mp 157-158°C (from hexane-ethyl acetate), R f 0.62, 0.91 (hexane-ethyl acetate, 1 : 1). IR spectrum: ν 1691 cm -1 (C=O). 1 H NMR spectrum (CDCl 3 ), δ, ppm: trans isomer: 1.69 s (3H, Me), 1.80 d.d (1H, endo-10-H, J 9a, endo-10 = 9.0, 2 J = 11.8 Hz), 1.86 m (1H, 1-H), 2.07 d.d (1H, exo-10-H, J 9a, exo-10 = 3.5, 2 J = 11.8 Hz), 2.65 m (1H, 1-H), 2.89 m (1H, 13c-H), 3.72 d.d (1H, 9a-H, J 9a, exo-10 = 3.5, J 9a, endo-10 = 9.0 Hz), 3.86-3.95 m (2H, 2-H), 4.42 d (1H, 13b-H, J 13b, 13c = 2.7 Hz), 5.36 d (1H, 3a-H, J 3a,13c = 8.2 Hz), 6.33 d ( 1H, J 12, 13 = 5.7 Hz), 6.54 d (1H, J 12, 13 = 5.7 Hz), 7.17 d.t (1H, J 4, 5 = J 5, 6 = 7.7, J 5, 7 = 1.1 Hz), 7.32 d.d (1H, J 5, 6 = 7.7, J 6, 7 = 8.1 Hz), 7.42 br.d (1H, J 4, 5 = 7.7 Hz), 8.03 d.d (1H, J 5, = 1.1, J 6, 7 = 8.1 Hz); cis isomer: 1.64 s (3H, Me), 1.71 d.d (1H, endo-10-H, J 9a, endo-10 = 8.7, 2 J = 11.8 Hz), 1.86 m (1H, 1-H), 1.99 d.d (1H, exo-10-H, J 9a, exo-10 = 3.6, 2 J = 11.8 Hz), 2.70 m (1H, 1-H), 3.11 m (1H, 13c-H), 3.66 d.d (1H, 9a-H, J 9a, exo-10 = 3.6, J 9a, endo-10 = 8.7 Hz), 3.84 m (2H, 2-H), 4.70 d (1H, 13b-H, J 13b, 13c = 2.5 Hz), 5.24 d (1H, 3a-H, J 3a, 13c = 7.2 Hz), 6.30 d (1H, 13-H, J 12, 13 = 5.7 Hz), 6.44 d (1H, 12-H, J 12, 13 = 5.7 Hz), 7.11 d.t (1H, 5-H, J 4, 5 = J 5, 6 = 7.7, J 5, 7 = 1.1 Hz), 7.24 d.d (1H, 6-H, J 5, 6 = 7.7, J 6, 7 = 8.4 Hz), 7.48 br.d (1H, 4-H, J 4, 5 = 7.7 Hz), 8.66 d.d (1H, 7-H, J 5, 7 = 1.1, J 6, 7 = 8.4 Hz). Mass spectrum, m/z (I rel , %): 309 (18) [M] + ,