Benzoxazine dimers

Both phenylhydrazones and imines derived from 5-halogeno-2-hydroxyacetophenones 510 were cyclized to the corresponding 4-methylene-substituted l,3-benzoxazin-2-ones 194 and 511 on treatment with 0.5 or O.bequiv of triphosgene under mild conditions (Scheme 96) <2003X8163, 2004SC71>. In the similar reactions of arylhydra-zones of 2-hydroxyacetophenones with 1 equiv of triphosgene, spiro-l,3-benzoxazine dimers were formed <2002JCM473>. 

A comparatively long N- -H hydrogen bond length in the benzoxazine dimer (see below), measured using an advanced solid state NMR technique (DIP-HSQC),has been reported [52]. This technique employs REDOR-type recoupling under fast MAS to recouple the heteronuclear - N dipolar interaction, such that rotor-encoded spinning sideband patterns are obtained. 

Finally, the N- -H distance in the hydrogen bonding arrangement adopted by a pair of methyl-substituted benzoxazine dimers has been determined by solid state NMR to be 1.94 A [148]. 

As a first example, we show how rotor-synchronized H DQ MAS spectra can distinguish between the solid-state hydrogen-bonded structures adopted by two different alkyl-substituted benzoxazine dimers [7V,./V-bis(3,5-dimethyl-2-hydroxybenzyl) R amine, where R = methyl or ethyl], 1, in the solid state.21... 

Figure 17. (a) The H (500.1 MHz) MAS (vr = 35 kHz) spectra of the methyl (solid line) and ethyl (dashed line) benzoxazine dimers, 1. (b, c) The low-field regions of rotor-synchronized H DQ MAS spectra of (b) the methyl and (c) the ethyl dimers, (d, e) Schematic representations of the proposed arrangement of (d) the methyl dimers into pairs, and (e) the ethyl dimers into a chainlike structure. (Adapted with permission from Figures 1, 5, 6, 8, and 9 of ref 21, Copyright 1998 American Chemical Society.)... 

On heating, the dichlorooxazolo[3,4- ]azepine 26, for which dimerization is prevented by the chloro groups, undergoes ring contraction and aromatization, involving a [l,2]-chlorine shift, to 5,8-dichloro-l,4-dihydro-2//-3,l-benzoxazin-2-one (27).11,153... 

The reaction of benzoxazine in die presence of 2,6-xylenol does not occur until 135 C, presumably because die hydrogen-bonded intermediate depicted for the 2,4-xylenol reaction (Fig. 7.19) cannot occur. All three types of linkages are obtained in diis case. Para-para methylene-linked 2,6-xylenol dimers, obtained from the reaction of 2,6-xylenol with formaldehyde, formed in the decomposition of the benzoxazine (or with other by-products of that process) dominate. Possible side products from benzoxazine decomposition include formaldehyde and CH2=NH, either of which may provide the source of methylene linkages. Hie amount of ortho-para linkages formed by reaction of 2,6-xylenol with benzoxazine is low. Ortho-ortho methylene-linked products presumably form by a decomposition pathway from benzoxazine (as in Fig. 7.18). 

A difunctional bisphenol-A-based benzoxazine has been synthesized and characterized by GPC and 1II NMR (Fig. 7.39). A small of amount of dimers and oligomers also formed. Thermal crosslinking of bisphenol-A benzoxazine containing dimers and oligomers resulted in networks with relatively high Tgs. Dynamic mechanical analysis of the network showed a peak of tan 8 at approximately 185°C. 

Oxidative cyclization of the 2-(morpholinomethyl)phenol 394 by use of Pb02 resulted in the 1,3,4,11 -tetrahydro-6/7-[l,4]oxazino[3,4+][l,3]benzoxazine 388 along with a dimeric minor product 395 (Equation 45). The structure of 388 was supported by X-ray crystallography <1997RCB1272>. 

An electrochemical cyclization leading to both benzoxazines and dihydrobenzoxazines is shown later in this section (Scheme 34). Finally, oxazine 304 was formed in a reductive, dehydrative dimerization of 303 (Scheme 33) <1961CIL254>. 

Dihydro-1,3-benzoxazines (196) are formed by the reaction of phenols with a mixture of formaldehyde and primary aromatic amines in the molar ratio 2 1. Presumably the phenol first reacts with the appropriate iminium species to form an intermediate amine (195), which is then cyclized in a Pictet-Spengler type reaction (Scheme 81) (44JA1875). If 2-hydroxybenzylamines are employed then methylene derivatives are obtained, and if the formaldehyde is replaced by a-dicarbonyl compounds dehydro dimers (197) are produced (Scheme 82) <70BCJ226>. 

Aminoacetophenones (265) when reacted with thiophosgene in a mixture of chloroform, water, and calcium carbonate form the corresponding isothiocyanates (266), but these spontaneously cyclize to afford 4-methylene-3,l-benzoxazine-2-thiones (267) which rearrange under the reaction conditions to yield 4-methylene-3,l-benzothiazin-2-ones (268). These products then slowly dimerize to 4-(3,l-benzothiazine-4-yl)methylene-3,l-benzothiazines (269) (Scheme 51) <9UHC1091>. 

The transition metal-catalyzed reductive carbonylation of o-substituted nitrobenzenes is a useful method for the synthesis of nitrogen heterocycles. Application of this methodology to the preparation of l,4-dihydro-2/f-3,l-benzoxazin-2-one derivatives and to the synthesis of the 3,1-benzox-azepin-2-one (42) has been reported <93JOM(451)157>. Reaction of 2-(2-nitrophenyl)ethanol (41) (100% conversion) with carbon monoxide in the presence of a palladium(Il) catalyst gave (42) in 60% yield, together with some of the macrocyclic dimer (43) ( nation (2)). It is suggested that a nitrene complex may not be involved with the palladium catalyst in view of the reaction path selectivity observed <93JOM(45i)l57>. 

Pyrolysis of benzoxazin-2-one (52) affords diazocine (27 R = H) in ca. 8% yield, reportedly as a result of dimerization of the first-formed biradical (Scheme 12) <87BCJ4417>. However, o-amino-benzophenone is the major product of this pyrolysis (49%) and, given the known self-condensation of such compounds to dibenzodiazocines (27 R = H), may represent a secondary product of this pyrolysis. 

Possible Structures of Dimers Contained in 3,4-Dihydro-3-methyl-l, 3-benzoxazine Product (from ref [131])... 

This reaction is an autocatalytic one. It is catalyzed by the dimers and higher oligomers with free ortho positions at the phenolic ring that are contained in the 3,4-dihydro-3-substituted- 1,3-benzoxazine precursors. Acids catalyze the reaction in equation 44 with adipie aeid showing the best performanee [133]. 

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