Benzoxazines rearrangement

Treatment of 7V-benzyl-l,2-benzisoxazolin-3-one with base produced a benzoxazine-4-one (see Scheme 88). The base catalyzed rearrangement of the 2-methyl-3-phenyl-l,2-benzoisoxolium salt to an oxazine is believed to proceed via a similar intermediate (67AHC(8)277). A number of other decompositions could possibly proced via this proposed route (74HCA376, 67AHC(8)277), which has also been postulated for the rearrangement of a variety of isoxazolium salts, e.g. the conversion of (200) into (202) (Section 4.16.3.3.2(i)(b)). 

Benzoxazines are heterocyclic compounds obtained from reaction of phenols, primary amines, and formaldehyde.98,99 As described previously, they are key reaction intermediates in the HMTA-novolac cure reaction.40,43 Crosslinking benzoxazine monomers at high temperatures gives rise to void-free networks with high Tgs, excellent heat resistance, good flame retardance, and low smoke toxicity.100 As in HMTA-cured novolac networks, further structural rearrangement may occur at higher temperatures. 

Thermal decomposition of l,2-dihydro-477-pyrrolo[2,l-r-][l,4]benzoxazine-l,2,4-triones 425 yielded 7-(2,4,6-trimethylbenzoyl)-8-[(2,4,6-trimethylphenoxycarbonyl)-6,10-dihydropyrido[2,l-r-][l,4]benzoxazine-6,10-dione by [4+2] cycloaddition of the initially formed ketene 426 and the subsequent rearrangement of 6,8,9,10-tetrahydropyrido[2,l-c][l,4]benzoxazine-6,8,10-trione 427 (Scheme 36) <1999RCB2131>. 

The 2-(2,4,6-triiodophenoxy)acetamide 399 on treatment with NaOMe underwent Smiles rearrangement to 400, which cyclized intramolecularly to the 2,3,5,6-tetrahydro-3-oxo-[l,4]oxazino[4,3,2-. 

The constitutionally isomeric 3-substituted (l//,3//)-quinazoline-2,4-diones and 2-phenylimino-4//-3,l-benzoxazin-4-ones are easy to distinguish via their El mass spectra (93RCM374). For quinazolinediones, the most striking feature is the loss of CO2, proving that a rearrangement due to anilino migration must occur. 

Chandrasekhar and colleagues used Af-acyl-Af, 0-bis(ethoxycarbonyl)hydroxylamines in a similar procedure to prepare amines. Aromatic Af-hydroxyimide derivatives were used by Marzoni and Varney " and Giitschow " to synthesize benz[crf]indol-2(l//)-one and 1-benzoxazin-4-one derivatives, respectively, via Lossen rearrangements. Both Af-benzyloxy and A-mesyloxy derivatives were used. 

In the thermal cyclization of 3-alkoxyphenyl A -(l-aryl-2,2,2-trifluoroethylidene)carbamates 287, obtained from 3-alkoxyphenols 285 and l-aryl-l-chloro-2,2,2-trifluoroethyl isocyanates 286, 2-aryl-2-trifluoromethyl-2,3-dihydro-477-l,3-benzoxazin-4-ones 290 were formed instead of the regioisomeric l,3-benzoxazin-2-ones 288 (Scheme 53). The formation of 290 was explained by a thermal isomerization of 287 involving a skeletal 1,3-rearrangement of the electron-rich aryloxy group to the azomethine carbon, which is electron deficient due to the electron-withdrawing CF3 group <2002JFC(116)97>. 

Whereas the Hofmann rearrangement of the amidoalcohols 452 with the usual NaOCl did not occur, reaction of the oxygen-bridged 452 (X = 0) with bis(acetoxy)iodobenzene under mild conditions led to a 9 1 mixture of the corresponding cyclic and acyclic carbamate derivatives 197 and 453 (X = 0) (Equation 50). In the similar reaction of the methylene-bridged analog 452 (X = CH2), the product of perhydro-3,l-benzoxazin-2-one type 197 (X = CH2) was obtained exclusively <20030PP429>. 

A reinvestigation of the experiments on the UV irradiation of l-acetyl-l,2-dihydroquinoline-2-carbonitriles (Reissert compounds) 561 unequivocally demonstrated that the rearrangement via the diradical intermediate 562 gave 4//-3,l-benzoxazines 563 and 565 rather than the benzazete derivatives described earlier. The yields and the type of products were strongly influenced by the substituent R at position 4 while irradiation of the unsubstituted quinoline 561 (R=H) gave 3,1-benzoxazine 563 in nearly quantitative yield, the amount of the corresponding methyl-substituted analog 565 that could be isolated was considerable lower, due to its irreversible isomerization via 562 to the stable cycloprop[/ ]indole derivative 564 (Scheme 107) <199811(49)121 >. 

Aminopyridine can be prepared by the reaction of 4-chloro-l,3-benzoxazines (47) with pyridine TV-oxides. Here it is proposed that an ion or radical pair is formed initially, which through displacement of hydrogen chloride and rearrangement leads to an TV-substituted benzoxazine (48). Finally, acid hydrolysis gives 2-aminopyridine and salicylic acid (49 Scheme 14) (80CPB465). 

Dihydro-2//-1,3-oxazines and -benzoxazines are stable to cold aqueous alkali, but hot dilute acids effect ring scission. In the monocyclic series the products are the salts of 3-aminopropyl esters (71) which rearrange to 3-hydroxypropylamides on basification. Should there be an aryl group at position 6 in the starting material, rearrangement is often followed by dehydration to styrene derivatives (72 Scheme 24) (72AG(E)287). 

Base-catalyzed ring-expansion of benzisoxazolones (217) provides a general route to 2,2-dialkyldihydro-l,3-benzoxazin-4-ones (218) (78CPB549) and the 2,4-dione (220) can be prepared by a Beckmann rearrangement of the oxime (219) (02CB3647). 2-Thion-4-ones (222) are formed from salicylic acids (221) by treatment with triphenylphosphine diisothiocyanate in dichloromethane at -40 °C (78CI(L)806). 

Treatment of 3-phenyl-l-oxo-l//-pyrido[2,l-c][l,4]oxazinium bromide with NH4OAc in AcOH, then with AC2O yielded l-hydroxy-3-phenylpyrido[ 1,2-a]pyrazinium bromide (64CB3566). 6,10-Dioxo-6,10-dihydropyrido[2,l-c][l,4]benzoxazine-7,8-dicarboxylate was rearranged into l-(2-hydroxyphenyl)-2-oxo-l,2-dihydropyridine-4,5-dicarboxylate by heating in DMF [85H(23)2401 89JHC847]. 

Deprotonation can occur at the -GH of pyrazole A-alkyl groups for example 1-methylpyrazole with -BuLi. Such proton loss is facilitated in cationic azido rings, and the ylides so formed sometimes undergo rearrangement. Thus, quaternized 1,2-benzisoxazoles 796 lose a proton and then rearrange to 1,3-benzoxazines, e.g., 797. Quaternized derivatives of benzofuroxan formed in situ undergo rearrangement to 1-hydroxybenzimidazole A-oxides 798. Reactions of this type are also known for A-alkylazolinones. 

While the acylanthranils belong to another ring system, examples of 3-acyl-substituted anthranils are known (Section III,C, 6, a) one of them (3-benzoylanthranil) rearranges on heating into the isomeric 2-phenyl-3,l-benzoxazin-4-one [Eq. (19)].165... 

---