Benzoxazines formation

Novolaks. Novolak resins are typically cured with 5—15% hexa as the cross-linking agent. The reaction mechanism and reactive intermediates have been studied by classical chemical techniques (3,4) and the results showed that as much as 75% of nitrogen is chemically bound. More recent studies of resin cure (42—45) have made use of tga, dta, gc, k, and nmr (15). They confirm that the cure begins with the formation of benzoxazine (12), progresses through a benzyl amine intermediate, and finally forms (hydroxy)diphenyknethanes (DPM). 

Although there is very little scope for reactions of the above types with 1,2-benzisoxazole derivatives, the quaternary salts such as 2-methyl-3-phenyl-l,2-benzisoxazolium salt underwent base-catalyzed isomerization to the 1,3-benzoxazine shown in Scheme 83. This reaction is analogous to the formation of (202) above (67AHC(8)277). 

Benzoxazinones pyrolysis, 3, 998 Benzoxazinones, dihydro-benzazetidine formation from, 7, 277 Benzoxazin-4-ones, dihydrosynthesis, 3, 1028... 

The polybenzoxazines (PBZs) provide a new class of phenolic resins that were first described by Ishida in 1998 (Ref. 15). Synthesis of the resins involves three components a phenol, a primary amine and formaldehyde. The first stage involves the formation of a multifunctional benzoxazine monomer Figure 23.30 a)). The monomer can then be ring-opened at elevated temperatures (160-220 C) to yield a polymeric stmcture (Figure 23.30(b)). 

Reaetion of l,3-benzoxazin-4-ones (43, 44) or trithioisatoie anhydride (45) with amidrazones (46, 47) or thiosemiearbazide (48) resulted in the formation of 3-(l-amidino)- (49-51) and 3-(l-thioureido)pyrimidines (52) respeetively. Compounds 49-52 underwent thermal intramoleeular ey-elization to the eorresponding l,2,4-triazolo[l,5-c]quinazolines (53-56) [68CB2106 76MI1 80PHA582 83MI1 85H(23)2357] (Seheme 18). 

Lim et al. also investigated HMTA-phenolic reactions with somewhat larger model compounds (e.g., two- and four-ring compounds) and established that similar reaction pathways to those described previously occurred.50 For these model compounds (as opposed to one-ring model compounds), which are more representative of typical oligomeric systems, increased molecular weight favored die formation of hydroxybenzylamines but not benzoxazines. This was suggested to be a steric effect. 

Irradiation of o-acetamidophenylacetylene (306) in hexane or acetonitrile results in intramolecular addition and the formation of the benzoxazine... 

In 1984, we demonstrated that A-alkoxy-A-acyl nitrenium ions 15 could be generated by the reaction of A-alkoxy-A-chloroamides 14 with Lewis acids such as Ag + and Zn2+ and used these to form heterocycles by intramolecular aromatic substitution reactions (Scheme 2).90 In this manner, several novel A-acyl-3,4-dihydro-2,l-benzoxazines 16a and A-acyl-4,5-dihydro-( I //,3//)-2,1-benzoxazepines 16b were made. Subsequent work91,92 and that of Kikugawa93 96 produced numerous syntheses involving alkoxynitrenium ions including formation of natural products.97 99... 

Tandem mass spectrometry has been used to demonstrate that M+ as well as MH+ of substituted A-(ort/zo-cyclopropylphenyl)benzamides isomerizes before the fragmentation, with formation of 3-aryl-1-ethyl-lH-benzoxazines and 5-ethyl-2-oxodi-benzoazepines (Scheme 5.14). The methyl group in /V-[ortho-( 1 -methylcvclopropyl )-phenyl]benzamides quenches the latter process, leaving the formation of benzoxazines as the only cyclization reaction. A subsequent chemical experiment in solution confirmed the mass spectral predictions [24]. A similar study confirmed the analogy of cyclization of substituted A-(ort/zo-cyclopropylphenyl)-A -aryl ureas and N- ortho-cyclopropylphenyl)-A -aiyl thioureas in the ion source of mass a spectrometer and in solution [25]. 

Alkylation of 2-hydroxyanilides with 1,2-dibromoethane under soliddiquid phase-transfer catalytic conditions leads to the formation of A-acyl 3,4-dihydro-2//-l,4-benzoxazines (Scheme 5.11) and optimum yields are obtained when a mixed organic phase of acetonitrile dichloromethane (4 6) is used [43]. No reaction occurs in dichloromethane and a complex mixture of products results, when acetonitrile is used alone. 

The El fragmentation patterns of 2-A-phenyliminooctahydro- 367 and -1,4,4a,5,8,8a-decahydro-5,8-methano-2//-3,l-benzoxazines 368 (94JHC893) indicate that the diexo/endo-isomenc unsaturated compounds 368 cannot, whereas the saturated 367 can, be differentiated on the basis of their El mass spectra. The former decomposed mainly in two consecutive RDA reactions, whereas the latter fragmented through several pathways, including the formation of ions [M-H] through intramolecular cyclization. 

Reversing the CH=N group position in 477-5,6-benzoxazin-4-one should result in the same isomerization enthalpy as from HC(NMe)OMe to MeCHNOMe. The enthalpy of formation of the latter species was calculated to be —7.1 kJmoR from the high-level quantum chemical calculations of Reference 4. The enthalpy of formation of the former species is unknown. However, if we accept the gas phase isomerization enthalpy of dimethylamides to methyl imidates (69.6 13.4 kJmoR ) in equation 52 from Reference 75,... 

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>. 

Treatment of the (—)-menthone-derived 2/7-1,3-benzoxazin-4(3//)-one 202 with triflic anhydride gave the triflate 203 in quantitative yield. Palladium-catalyzed cross-coupling of 203 with 2-pyridylzinc halide resulted in formation of an approximately 3 1 mixture of the 4-(2-pyridyl)-2//-l,3-benzoxazine 204 and a 4-imino-l,3-benzodioxane derivative 205 (Scheme 36). Compound 205 was formed by the isomerization of 203, which occurred with complete retention of stereochemistry. The 4-(2-pyridyl)-l,3-benzoxazine derivative 204 was applied in enantioselective allylic alkylations of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate as a chiral ligand inducing a 62% ee in the product <2005JOM(690)2027>. 

In the reactions of the perhydro-l,3-benzoxazine derivatives 236 with benzeneselenyl chloride in dichloromethane-methanol, methoxyselenylation of the double hond in the C-2 side chain occurred in a highly regio- and diastereo-selective way (Scheme 43). Reductive deselenylation of 237 with triphenyltrn hydride in the presence of a catalytic amount of azobisisobutytonitrile (AIBN) resulted in formation of the methoxy derivatives 238 <2006JOC2424>. 

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