Benzoquinone methides

Preparation of 3-Methyl-4H-1,2-Benzoxazine and Its Reactivity as a Precursor of o-Benzoquinone Methide. 

Several types of 1,2-oxazines undergo thermal pericyclic reactions in which the N—O bond is cleaved. Thus (506, R = Me, Ph) undergo a thermal retro Diels-Alder reaction on heating to give the corresponding nitrile and o-benzoquinone methide, which can be intercepted by alkenes (Scheme 56) (90JA5341, 94TL7273). 

The same intermediate occurs in the Lehmann method463 for converting the methiodides of phenolic Mannich bases into 2,3-dihydrobenzo-furans, through reaction with dimethyloxosulfonium methylide. Thus, o-benzoquinone methide (207) leads to 2,3-dihydrobenzofuran according to Scheme 4. Similarly, 2-naphtholgives l,2-dihydronaphtho[2,l-6]furan through 208 and 209, formed and rearranged in situ.i6i The reaction has been applied to the synthesis of polycyclic benzofurans.483,485... 

The simpler substrate o-benzoquinone methide (5) affords (6), but only in 127o yield. 

No new TV-benzyltetrahydroisoquinolines have been isolated from natural sources in recent years. However, the structure of corgoine has been confirmed by three syntheses. The first involves reduction of the 7V-benzyl quaternary salt derived from isoquinoline 1, whereas the second approach utilizes the Pictet-Spengler reaction to cyclize the substituted phenethylamine 2 (see Scheme 31.1). The third synthesis of corgoine involves heating 6-methoxy-7-hydroxy-tetrahydroisoquinoline with / -hydroxybenzyl alcohol to afford the alkaloid in 44% yield. The A -benzylation probably occurs through the intermediacy of /7-benzoquinone methide which adds to the basic nitrogen of the isoquinoline. ... 

FIGURE 6.18 Oxidation of ortAo-methylphenols to the corresponding ortho-quinone methide via transient zwitterionic intermediates that are stabilized by forming a complex 19 with the 2,5-dihydroxy[l,4]benzoquinone-derived bis(sulfonium ylide). 

Patel, A. Netscher, T. Rosenau, T. Stabilization of ortho-quinone methides by a bis (sulfonium ylide) derived from 2,5-dihydroxy-[l,4]benzoquinone. Tetrahedron Lett. 2008, 49, 2442-2445. 

The anion derived from 2,3-dimethyl-l,4-naphthoquinone behaves as a quinone methide and undergoes a [l,4]-cycloaddition with the benzoquinone (193). The product is the xanthene derivative (194) (70JCS(C)722). There is no indication of the formation of the isomeric xanthene. A [l,3]-cycloaddition occurs simultaneously which leads to the fluorene derivative (195). 

Bispyrano-l,4-benzoquinones 18 are readily formed regioselectively but as separable diastereomers when a mixture of 2,5-dihydroxy-l,4-benzoquinone, paraformaldehyde and an electron-rich alkene is heated under microwave irradiation. A double domino Knoevenagel -HDA is involved with generation of an o-quinone methide type of intermediate <07T3066>. 

Quinones - Quinone methides are produced on irradiation of /7-benzoqui-nones in the presence of the eneyne (267) in methylene chloride as solvent. 1,4-Naphthoquinones also afford quinone methides but unstable spirooxetenes were also detected. The photochemical addition of phenanthraquinone and ace-naphthenequinone to eneynes has also been studied. 1,4-Benzoquinones undergo addition to electron donating alkenes to yield spirooxetanes. The resultant cyclohexadienones are themselves photochemically reactive and irradiation converts these into dihydrobenzofurans via a dienone-phenol rearrangement. " ... 

Trimethylphenol (221) was oxidized with dioxygen catalyzed by CuCl2-2H20 to afford 3,5-dimethyl-4-hydroxybenzaldehyde (222) and 2,6-dimethyl-p-benzoquinone (223) in low yields. However, the use of acetone oxime as an additive caused a dramatic change to afford both 222 and 223 in 91.5 and 6.5% yields, respectively . These oxidation products are formed from p-quinone methide 225 through 2,6-dimethyl-4-(hexyloxymethyl)phenol (224) (Scheme 45). 

The effect of benzoquinones on thermal oxidation of hydrocarbons was investigated in detail on a liquid substrate. It was found182 that 4-tert-alkyl-l,2-benzoquinones are at 60 °C more powerful retarders in the initiated oxidation of tetra-hydronaphthalene than 2-tert-alkyl-l,4-benzoquinones. The effect of both isomeric hydroxy-tert-alkylbenzoquinones of types CXLin and CLI on this oxidation is entirely negligible. Unsubstituted 1,4-benzoquinone retards the oxidation of ethylbenzene213. However, the retardation effect of 2-tert-butyl- and 2,6-di-tert-butyl-1,4-benzoquinones CXXXVIII and XXII and, in particular, of 3,5,3 -tetra-tert-butyl-4,4 -diphenoquinone XX is much weaker than that of derivatives of quinone methide, e. g., XXIX Moreover, benzoquinones resume their retardation... 

An induction period was observed in the decomposition of cumyl hydroperoxide in chlorobenzene at 70 and 110 °C in the presence of phenolic sulphides CXCVIIa,b262). This was a substantial difference with respect to the behaviour of 4,4 -thio-bis(2,6-di-tert-butylphenol) CLXVIIIb which decomposed ROOH under the same conditions without induction period. The result indicates a mechanistic distinction in the action of both types of phenolic sulphides. In the mechanism of transformations of benzyl sulphide CXCVIIb, there are assumed (Scheme 24) the formation of sulphoxide CXCVIII and the intermediary formation of CIC followed by oxidation and formation of sulphinic acid CC. Further transformation of the acid CC depends on the character of R. If R = 3,5-di-tert-butyl-4-hydroxybenzyl, as it is in the formation of CC from CXCVIIa, the total elimination of the sulphurous part of molecule may occur and the transformation products of phenolic or quinoid character may be formed 3,5-di-tert-butyl-4-hydroxybenzyl alcohol XXXI, the corresponding aldehyde XXXII, and 2,6-di-tert-butyl-l,4-benzoquinone XXII were identified. Another possible sulphurless product is 4,4 -ethylenebis(2,6-di-tert-butyl-phenol) XXVIII, which was isolated in small amounts in its oxidized form as 3,5,3 ,5 -tetra-tert-butyl-4,4 -stilbenequinone (XXIX). Quinone methide XXX formed by thermolysis of sulphoxide CXCVIII, may be also the precursor in formation of XXIX. According to66), XXX is further oxidized by hydroperoxides to XXIX... 

QMs exist in three isomeric forms, namely, o-, m-, and p-quinone methides (also known as o-, m-, and p-QMs) (Figure 7.5). The importance of o- and p-QMs in organic synthesis and their role in biochemistry have been studied in detail. Urdike benzoquinones, o- and p-QM derivatives are highly polarized compounds, usually observed with difficulty or postulated as reactive intermediates because of facile reactions driven by the formation of aromatized phenol derivatives. 

To a quartz cuvette fitted with a Teflon stopcock was added 53 mg 2,6-dichloro-benzoquinone and 63 mg phenyl m-xylyl acetylene in CH2CI2 in a 0.1 M solution of each substance under argon. The cuvette was then placed in a clear Dewar flask filled with water at 25°C and irradiated with focused light from a medium-pressure mercury lamp (500 W) passed through an aqueous IR filter and an ESCO 410 nm filter. This ensured that the quinone itself was excited and not the diarylacetylene. After 22 h, the solvent was evaporated, and the residue was subjected to flash chromatography. 1-(3,5-Dimethylphenyl)-l-benzoyl-1-methylene-3,5-dichlorocyclohexa-2,5-dien-4-one was obtained as the major product, which was further recrystallized from acetonitrile, m.p., 191-192°C. The minor product was identified only by GC/MS. The total yield of quinone methide was 88% based on 62% of conversion. 

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