Quinones ortho

The student should note that ketones in class (1), t.c., those having the >CO group in the side chain, will form additive compounds with sodium bisulphite only if this >CO group is not directly joined to the benzene ring acetophenone therefore will not form such compounds, whereas benzyl methyl ketone, CaHsCHjCOCH, will do so. Many quinones, particularly ortho quinones such as phenanthraquinone, form additive compounds with sodium bisulphite. 

Ortho quinones (and also aromatic a-diketones, o-phenylenediamine to yield quinoxalines as follows. 

Fenoldopam (76) is an antihypertensive renal vasodilator apparently operating through the dopamine system. It is conceptually similar to trepipam. Fenoldopam is superior to dopamine itself because of its oral activity and selectivity for dopamine D-1 receptors (D-2 receptors are as.sociated with emesis). It is synthesized by reduction of 3,4-dimethoxyphenylacetonitrile (70) to dimethoxyphenethylamine (71). Attack of diis last on 4-methoxystyrene oxide (72) leads to the product of attack on the epoxide on the less hindered side (73). Ring closure with strong acid leads to substituted benzazepine 74. O-Dealkylation is accomplished with boron tribromide and the catechol moiety is oxidized to the ortho-quinone 75. Treatment with 9NHC1 results in conjugate (1,6) chloride addition and the formation of fenoldopam (76) [20,21]. 

B. Naphthaquinone method Discussion. Many primary amines develop a blue colour when treated with ortho-quinones the preferred reagent is the sodium salt of l,2-naphthaquinone-4-sulphonic acid. 

The ortho-quinone methides are difficult to isolate due to their high reactivity, which leads to rapid Diels-Alder dimerization or trimerization (Fig. 7.26). At 150°C, a partial retro-Diels-Alder reaction of the trimer can occur to form ortho-quinone methide and bis(2-hydroxy-3,5-dimethylphenyl) ethane (dimer).51... 

Figure 7.26 Dimer and trimer structures of ortho-quinone methides.

Orthopedic fixations, 27 Ortho-quinone methides, 400, 401 Oxalic acid, 379... 

An interesting combination of enzymatic with non-enzymatic transformation in a one-pot three-step multiple sequence was reported by Waldmann and coworkers [82]. Phenols 125 in the presence of oxygen and enzyme tyrosinase are hydroxylated to catechols 126 which are then oxidized in situ to ortho quinones 127. These intermediates subsequently undergo a Diels-Alder reaction with inverse electron demand by reaction with different dienophiles (Table 4.19) to give endo bicyclic 1,2-diketones 128 and 129 in good yields. 

The Husemann and Erdmann identification reactions for morphine and codeine in the DAB 9 (German Pharmacopoeia) involve the formation of the red-colored ortho-quinone (8) via apomorphine (5) under the influence of nitric acid with the simultaneous nitration of the benzene ring [15]. 

The symmetrical bis(ylidyl)phosphenium chlorides 103, obtained from the reaction of trimethylsilyl ylides 102 with PCI3 are the first phosphenium salts which do not need counterions of low basicity such as AICI4 to be isolated (Scheme 30) [119]. The explanation of their stability lies in the delocalisation of the phosphenium charge in the two phosphonium parts. The reactivity study of these species is reported and for example the phosphenium 103 (R=Ph) adds ortho quinones to the central phosphorus to give the corresponding dioxaphospholenium salts 104 via a [4-1-1] cycloaddition. 

Ortho quinones (and also aromatic a-diketones, e.g., benzil) react with o-phenylenediamine to yield quinoxalines as follows. Dissolve the substance... 

Pyrans and napthopyrans (chromenes) are photochromic compounds that undergo photochemically induced electrocyclic ring opening to give colored ortho-quinone methides.95-98 For example, chromene 153 opens on irradiation to give 154 (Eq. 1.41). 

Chiang, Y. Kresge, J. Zhu, Y. Flash photolytic generation of ortho-quinone methides in aqueous solution and study of its chemistry in that medium. J. Am. Chem. Soc. 2001,123, 8089-8094. 

FIGURE 6.4 Reactions and products of the primary oxidation intermediates of a-tocopherol (1), the tocopheroxyl radical 2, ortho-quinone methide 3, and chromanoxylium cation 4. 

FIGURE 6.9 Confirmed heterolytic formation pathway for 5a-a-tocopheryl benzoate (11) without involvement of 5a-C-centered radicals and its proof by trapping of ortho-quinone methide 3 with ethyl vinyl ether to pyranochroman 13. Shown are the major products of the reaction of a-tocopherol (1) with dihenzoyl peroxide. 

FIGURE 6.15 Detailed mechanism of the oxidation of or t/to-me thy I phenols to ortho-quinone methides by Ag2Q according to DFT computations.38... 

Thus, in complex 17, the stabilized ortho-quinone methide 3 was evidently not present in its traditional quinoid form, but in the form of a zwitterionic, aromatic... 

FIGURE 6.16 ortho-Quinone methide 3 stabilization of the zwitterionic rotamer in a complex with /V-methyImorpholine /V-oxide (17). The zwitterionic, aromatic precursor 3a affords the common quinoid form of the o-QM 3 by in-plane rotation of the exocyclic methylene group. 

The geometry of the zwitterions with its exocylic out-of-plane methylene group was quasi-preserved in the recently reported dibenzodioxocine derivative (18) that was formed in rather small amounts by rapidly degrading the NMMO complex at elevated temperatures.45 Strictly speaking, dibenzodioxocine dimer 18 is actually not a dimer of ortho-quinone methide 3, but of its zwitterionic precursor or rotamer 3a (Fig. 6.17). As soon as the out-of-plane methylene group in this intermediate rotates into the ring plane, the o-QM 3 is formed irreversibly and the spiro dimer 9 results... 

FIGURE 6.17 Oxidation of a-tocopherol (1) conventionally leads to its spiro dimer (9) via ortho-quinone methide 3 (path A). The zwitterionic o-QM precursor 3a is stabilized by NMMO in complex 17, which upon rapid heating produces small amounts of new dioxocine dimer 18 (path B). Acid treatment of 18 causes quantitative conversion into spiro dimer 9, via o-QM 3 (path C). 

It was shown that complexes 19 of the zwitterionic precursors of ortho-quinone methides and a bis(sulfonium ylide) derived from 2,5-di hydroxyl 1,4 benzoquinone46 were even more stable than those with amine N-oxides. The bis(sulfonium ylide) complexes were formed in a strict 2 1 ratio (o-QM/ylide) and were unaltered at —78 °C for 10 h and stable at room temperature under inert conditions for as long as 15—30 min (Fig. 6.18).47 The o-QM precursor was produced from a-tocopherol (1), its truncated model compound (la), or a respective ortho-methylphenol in general by Ag20 oxidation in a solution containing 0.50-0.55 equivalents of bis(sulfonium ylide) at —78 °C. Although the species interacting with the ylide was actually the zwitterionic oxidation intermediate 3a and not the o-QM itself, the term stabilized o-QM was introduced for the complexes, since these reacted similar to the o-QMs themselves but in a well defined way without dimerization reactions. 

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). 

REACTIONS OF THE COMMON TOCOPHEROL-DERIVED ORTHO-QUINONE METHIDE 3... 

FIGURE 6.42 Oxidation of 3-oxa-chromanol 58 in the presence of 1 equivalent of water mechanistic study hy means of selectively deuterated starting material. The initially formed ortho-quinone dimethide 63 rearranges into styrene derivative 64, which then reacts with water to provide acetophenone 61. 

Selected Substituent-Stabilized Tocopherols and Conjugatively Stabilized Ortho-Quinone Methides... 

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