Naphthoxazine

The H NMR spectra of la-f and 3d-c, 3d-a, 3d-b, 3e-b, 3e-f proved that, in DMSO solution. Each set of compounds formed three-component ring-chain tautomeric mixtures, containing epimeric naphthoxazines together with the open-chain tautomer. Compounds displayed singlets at 8 5.40-6.32 due to NphCHArNH 8.41-8.73 due to NH = CHAr. 

To the oily or crystalline naphthoxazines, la-f (1 mmol) and 20% HCl (20 mL) were stirred and refluxed for 3 hours. The solvent was evaporated and the oily residue was crystallized from EtOAc (10 mL), and the obtained products, 2, recrystallized from a mixture of MeOH (1 mL) and Et O (10 luL). 

The commercially available spirooxazines are based on the spiroindolinonaphthoxazines (1.11) ring structure. The synthetic route to this ring system involves the reaction of a l-hydroxy-2-nitoso bearing aromatic ring with a 2-aUcylidene heterocycle, such as Fischer s base (1.6 R = H). The naphthoxazines are the derivatives of choice... 

The effects of both alkyl and aryl substituents can be observed in the two-component tautomeric equilibria of 3-alkyl-l-aryl-2,3-dihydro-177-naphth[l,2-r ][l,3]oxazines containing C-3-epimeric naphthoxazines 52B-58B and 52G-58C (Scheme 7). The influence of the Meyer parameters (V ) of the alkyl substituents on the epimerization constants (K d ( r= [B]/[G]) can be characterized by Equation (3). Multiple linear regression analysis of log A)r according to Equation (4) leads to the conclusion that these equilibria are also influenced significantly by the inductive effect of substituent Y 0.48) <2004JOC3645>. 

Fedorova, O.A., Gromov, S.P., Pershina, Y.V., Sergeev, S.S., Strokach, Y.P., Barachevsky, V.A., Alfimov, M.V., Pepe, G., Samat, A., Guglielmetti, R. (2000) Novel azacrown ether-containing spiro[indoline-2,3,-naphthoxazines] design, synthesis and cation-dependent photochromism, J. Chem. Soc., Perkin Trans. 2, 563-571. 

Extending these studies further, the absorption spectra of 6-nitro- and 6-bromoBIPS, and the indolinospiro(naphthopyran), (naphthoxazine) and (phenan-throxazine) were measured in 12 solvents of widely varying polarity, having ET values ranging from 32.4 (CC14) to 55.4 (MeOH), at several temperatures from 10 to 60°C. The effects of solvent polarity indicate that the colored form is quinoid-like if... 

Among the photodegradation products of l-alkyl-3,3-dimethylindolinospiro-naphthoxazines in toluene solution in air are the l-alkyl-3,3-dimenthyloxindole and... 

Table 2.4. Effects of Substituents Attached to the Naphthoxazine Moiety...

Benzannellation of the naphthoxazine moiety has been accomplished to yield compounds 8,9, and 10. The visible absorption band of the anthracene derivative 10... 

In the case of compound 19, the indoline and naphthoxazine moieties are linked by a bridged chain the configuration is relatively rigid even after cleavage of the C-0 in the oxazine ring. The ring-opened species can be observed in acetonitrile, but not in cyclohexane.15 The synthesis of compound 19 is given later. 

J. Hobley and F. Wilkinson, Photochromism of naphthoxazine-spiro-indolines by direct excitation and... 

Strong protic acids cleave phenolic methyl ethers. Thus hydrogen bromide accomplished the same double demethylation as that depicted in Scheme 4.104.189 The final step in a Merck synthesis of the potent dopamine agonist (A,R)-4-pro-pyl-9-hydroxy naphthoxazine (106 2), a phenolic ether deprotection was accomplished on a large scale using methanesulfonic acid in the presence of methionine as the nucleophile [Scheme 4.106]. 190 191... 

The rigidification of the dopamine molecule led to a number of dopamine receptor agonists in which the dopamine molecule, with its phenylethylamine moiety, is readily recognisable. In these dopamine agonists the amine moiety is either a part of a cyclic system, e.g. benzo[/]quinolines, naphthoxazines, and benzopyranoxazines, or an exocyclic amine, e.g. 2-aminotetralins and 2-aminoindans (Chart 1.5). 

Thiophene analogues of naphthoxazines and 2-aminotetralins bioisosteres with improved relative oral bioavailability, as compared to 5-OH-DPAT ... 

This chapter is based on Rodenhuis, N. Timmerman, W. Wikstrom, H.V Dijkstra, D. (2000) Thiophene analogs of naphthoxazines and 2-aminotetralins bioisosteres with improved relative oral bioavailability, as compared to 5-OH-DPAT. Eur. J. Pharmacol. 394, 255-263. 

Swart, P.J. Jansman, F.G.A. Drenth, B.F.H. de Zeeuw, D. Dijkstra, D. Horn, AS. (1991) Impact of structural differences on the in-vitro glucuronidation kinetics of potentially dopaminergic hydroxy-2-aminotetralins and naphthoxazines using rat and human liver microsomes. Pharmacol. Toxicol. 68, 215-219. 

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