5.6- Dihydro-2 /7-1,2-oxazines tautomerism

H-1,2-Oxazine, 3,6-dihydro-6-(2-pyridyl)-mass spectra, 2, 529 2H-1,2-Oxazine, tetrahydro-synthesis, 2, 92 4H-l,2-Oxazine, 5,6-dihydro-pyrolysis, 3, 999 synthesis, 3, 1017 tautomerism, 3, 999 4H-1,2-Oxazine, 5,6-dihydro-3-methyl-metallation, 1, 484 4H-l,2-Oxazine, 5,6-dihydro-3-nitro-reactions, 3, 1000 6H-l,2-Oxazine, 3,5-diphenyl-stability, 3, 997 synthesis, 3, 1014... 

By tautomerism the product can also be regarded as a 5,6-dihydro-l,3-4//-oxazine derivative (28b). 

Dihydro-2/7- 74 and -4//-l,2-oxazines and thiazines 75 are interrelated by prototropy, being enamines and imines, respectively. In the case of oxazines, the imine form 75 is favored, and there are several well established examples of this system, including the parent heterocycle 75 (X = O) [84MI2]. No tautomeric equilibrium between the 2H and 4H forms has been observed under normal conditions in solution or in the solid state. However, the formation of intermediate 2H isomers 77 was proposed both for the conversion of 3-phenyl-5,6-dihydro-4//-l,2-oxazine 76 (R = Ph, r = R = H) into 2-phenylpyrrole(89TL3471) under strong basic conditions and for thermal decomposition of cyclopentene-fused 1,2-oxazine 76... 

Aryl substituents on the 1,3-oxazine ring give rise to a characteristic effect on the two- or three-component ring-chain tautomeric equilibria of 2,3-dihydro-l//-naphth[l,2-< ][l,3]oxazines 35-44 and the regioisomeric 3,4-dihydro-2//-naphth[2,l-H[l,3]oxazines 45-51 (Scbeme 6). The major ring forms of the equilibria 36-51 contain the 1,3- or... 

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>. 

Reduction of cycloalkane-condensed 2-phenyl-5,6-dihydro-4//-l,3-benzoxazines 144 with lithium aluminium hydride (LAH) afforded A -benzyl-substituted 2-(aminomethyl)cycloalkanols 145 in a reductive ring opening via the ring-chain tautomeric tetrahydro-l,3-oxazine intermediates. Catalytic reduction of 1,3-oxazines 144 under mild conditions in the presence of palladium-on-carbon catalyst similarly resulted in formation of the A -benzyl-1,3-amino alcohols 145. When the catalytic reduction was performed at elevated temperature at hydrogen pressure of 7.1 MPa, the N-unsubstituted 2-(aminomethyl)cycloalkanols 146 were formed in good yields (Scheme 22) <1998SC2303>. 

An efficient and simple kinetic resolution of the racemic Betti base 387 was achieved via its reaction with acetone in the presence of L-(- -)-tartaric acid. When a suspension of racemic 387 in acetone was treated with L-(- -)-tartaric acid, the (A)-enantiomer formed a crystalline L-tartrate salt 389 this was filtered off, and the (iJ)-enantiomer could be isolated as a naphth[l,2-< ]oxazine derivative 388 from the filtrate (Equation 41). Both enantiomers were obtained in excellent yields and ee s. The enantioseparation is presumed to take place via a kinetically controlled N,0-deketalization of the (3)-naphth[l,2-< ]oxazine derivative <2005JOC8617>. An improved method for the enantioseparation of 387 was developed by the reaction of the ring-chain tautomeric l,3-diphenyl-3,4-dihydro-2//-naphth[2,l-< ][l,3]oxazine (41 X, Y = H) and L-(-f)-tartaric acid, yielding the crystalline 389 in 85% yield <2007SL488>. 

V-Unsubstituted dihydropyridines can exist in at least five tautomeric forms (Section 2.2.5.2). At least for /V-substituted compounds 1,4-dihydropyridines (cf. 453) are generally more stable, by ca. 9 kJ mol than the 3,4-dihydro and the 1,2-dihydro isomers (cf 454). By contrast 2/f-pyrans appear to be thermodynamically more stable than 4//-pyrans. All three types of 1,3-oxazine are known. 

Of the two possible tautomeric structures for monocyclic dihydro-1,4-oxazines and -thiazines the 3,4-dihydro-2/f-representation is preferred in which the ring has a half-chair conformation. 

According to Ignatova et a/.,125 2-iminotetrahydro-l,3-oxazines are tautomeric with 2-amino-5,6-dihydro-4//-l,3-oxazines [Eq. (23)]. 

Meyers et al.221-222 showed that tetrahydro-l,3-oxazines exist in tautomeric ring-chain forms [Eq. (62)]. When a 5,6-dihydro-l,3-oxazine is reduced to a tetrahydro-l,3-oxazine, some 3-aminoalcohol can also be formed through the reduction of the open-chain imino form [cf. Eq. (62)]. To avoid this the reduction should be carried out with sodium borohydride at - 40°C. 

As pointed out previously (Section II,B,l,e), 2-amino-5,6-dihydro-4H- 1,3-oxazines are tautomeric with 2-imino-tetrahydro-1,3-oxazines125... 

Ethoxy-5,6-dihydro-4//-l,3-oxazines (111) react with enolates and related compounds at C-2 ethanol is lost and the corresponding 2-substituted dihydro-1,3-oxazine is formed. Depending upon the nature of the substituent endo-exo double bond, tautomerism can be observed. Thus, a reaction with the anion of malononitrile yields the 2-alkylidene-3,4,5,6-tetrahydro-l,3-oxazine (112) rather than the 2-alkyl-5,6-dihydro-1,3-oxazine (113) (Scheme 27) <86JHC701>. 

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