1,4-Naphthoquinone 2,3-dimethyl

Dimethylbutadiene and 1 4-naphthoquinone. 2 3-Di-methylanthraquinone. In a small round-bottomed flask, fitted with a reflux condenser, place a solution of 8 g. of freshly-distUled 2 3-dimethyl-butadiene (Section 111,147) and 8 g. of 1 4-naphthoquinone (Section IV,149) in 30 ml. of ethanol, and reflux for 5 hours. Keep the resulting solution in a refrigerator for 12 hours break up the crystaUine mass, filter, and wash with 5 ml. of alcohol. The yield of crude adduct, m.p. 147-149°, is 11-5 g. recrystaUisation from methanol raises the m.p. to 150°. 

Determination of structural features. The ultraviolet spectrum has been of value in the determination of the structure of several vitamins. Thus the presence of an a-naphthoquinone system in vitamin K was first detected by this means. Also the 4-methylthiazole and the 2 5-dimethyl-6-aminopyridine system was first identified in vitamin Bj (thiamine), a- and /3-Ionones can be distinguished since the former contains two conjugated chromophores and the latter three conjugated chromophores. 

Donor substituents on the vinyl group further enhance reactivity towards electrophilic dienophiles. Equations 8.6 and 8.7 illustrate the use of such functionalized vinylpyrroles in indole synthesis[2,3]. In both of these examples, the use of acetyleneic dienophiles leads to fully aromatic products. Evidently this must occur as the result of oxidation by atmospheric oxygen. With vinylpyrrole 8.6A, adducts were also isolated from dienophiles such as methyl acrylate, dimethyl maleate, dimethyl fumarate, acrolein, acrylonitrile, maleic anhydride, W-methylmaleimide and naphthoquinone. These tetrahydroindole adducts could be aromatized with DDQ, although the overall yields were modest[3]. 

A = Acrylonitrile B = Benzoquinone C = Naphthoquinone D = 5,8-Quinolinequinone E = Methyl vinyl ketone F = Dimethyl acetylene dicarboxylate G = Methyl acrylate ... 

Typically, the synthesis of block B involves the Diels-Alder reaction of 1,4-naphthoquinone with cyclopentadiene, followed by reduction and OH methylation to give 92 (Scheme 33). The next step involves a Ru-catalysed [2+2] cycloaddition of 92 with dimethyl acetylenedicarboxylate (DMAD), followed by epoxidation (MeLi, BuOOH) to give 94 as block B. 

Whereas for the hexamethyl compound 150 only products formed by the linear route have been detected with a sizeable number of dienophiles (X=X inter alia TCNE, maleic anhydride, benzoquinone, 1,4-naphthoquinone, acrolein, methyl acrylate102), the parent system 4 undergoes threefold Diels-Alder addition in a star-shaped manner leading to 164 with dimethyl acetylenedicarboxylate and to 165 with fumaroyl chloride followed by methanolysis (equation 20)92. 

The generation and trapping of 5,6-bis(trimethylsilyl)benzo[c]furan 126 was reported by Wong utilizing Warrener s s-tetrazine methodology. The trapping of the silylated isobenzofuran with A-phenylmaleimide is illustrated below. A number of other dienophiles such as dimethyl acetylenedicarboxylate, benzoquinone, naphthoquinone and anthra-l,4-quinone have also been used <00TL5957>. 

Other mediators which have been used in combination with diaphorase for the regeneration of NAD+ are riboflavin and Vitamin K3, which is 2,3-dimethyl-1,4-naphthoquinone. However, especially riboflavin is not stable enough for synthetic applications [40]. Better stability is exhibited by phenanthrolindiones as mediators. In combination with diaphorase, Ohshiro [41] showed the indirect electrochemical oxidation of cyclohexanol to cyclohexanone using the NAD+ dependent HLADH with a turnover frequency of two per hour. For an effective enzymatic synthesis, this turnover frequency, however, would be too small. In our own studies, we were able to accelerate the NAD(P)+ regeneration considerably by lowering the electron density within the... 

Sanders, et al. Isolation and characterization of 2,3-dimethyl-6-(4,8,12-trimethyltridecyl) 1,4-naphthoquinone from tobacco, and smoke. Tetrahedron Lett 1978 1978 2645-2648. 

The pioneer work on this subject using simple 1-azadienes is due to Ghosez et al. (82TL3261 85JHC69) they succeeded in reacting 1-azadienes as 47r-electron components in Diels-Alder cycloadditions. Thus, l-dimethylamino-3-methyl-l-azabuta-l,3-diene (a,/3-unsaturated hydrazone) 54 did undergo [4 + 2] cycloaddition to typical electron-poor dienophiles, e.g., methyl acrylate, dimethyl fumarate, acrylonitrile, maleic anhydride, and naphthoquinone, producing pyridine derivatives 55-57 (Scheme 14). 

Di-C-a-L-arabinopyranosyltricin 8-Dichloroacetyl-2,7-dimethyl-5-hydroxy-l,4-naphthoquinone Tricin 6,8-di-C-arabinoside Mollisin... 

Another redox switchable system is based on dyad 21 in which 2-chloro-1,4-naphthoquinone is covalently attached to 5-dimethyl-aminonaphthalene via a non-conjugated spacer. The intrinsic fluorescence of the dansyl excited state in dyad 21 is strongly quenched, due to the intramolecular electron transfer from the excited dansyl to the adjacent quinone acceptor. However, the fluorescence can be switched on by addition of a reducing agent. Apart from chemical switching, the fluorescence of dyad 21 can also be switched electrochemically. This can be realized using a photoelec -trochemical cell, and the solution starts to fluoresce upon application of a reductive potential.31... 

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). 

Heating of a mixture of 2-phenyl-1,4-naphthoquinone (1 eq.) with dimethyl malonate (4 eq.) and manganese(III) acetate (6 eq.) in acetic acid at 80°C for 16 hours gives 1 in 76% yield, and this has been shown to be a general type of reaction for a variety of 2-aryl-l,4-naphthoquinones. 

Rhodium complexes with the derivatives of p-quinone (1,4-naphthoquinone and 2,3-dimethyl-l,4-benzoquinone) were also reported [236]. 

A synthesis of lapachol using reaction conditions better than those used by Fieser was carried out by Fridman et al [149].They used the lithium salt of 2-hydroxy-1,4-naphthoquinone prepared in situ instead of the silver salt used for Fieser [150]. The lithium salt was prepared in situ by addition of lithium hydride to the frozen solution of the quinone in dimethyl sulfoxide, Fig. (14). As the solution thawed, the lithium quinone was slowly formed and was then alkylated with 3,3-dimethylallyl bromide. Lapachol was thus obtained in 40% yield. 

Thus, Ghosez et al. were successful in showing that A,iV-dimethyl hydrazones prepared from a,/3-unsaturated aldehydes react smoothly in normal electron demand Diels-Alder reactions with electron-deficient dienophiles [218, 219]. Most of the more recent applications of such 1-aza-l,3-butadienes are directed towards the synthesis of biologically active aromatic alkaloids and azaanthra-quinones [220-224] a current example is the preparation of eupomatidine alkaloids recently published by Kubo and his coworkers. The tricyclic adduct 3-19 resulting from cycloaddition of naphthoquinone 3-17 and hydrazone 3-18 was easily transformed to eupomatidine-2 3-20 (Fig. 3-6) [225]. 

Methylbenzophenone gives, on photochemical bromination (refluxing CCI4), 2-bromomethylbenzophenone in 80% yield. When the bromination was conducted at room temperature and the crude product treated in refluxing CHCI3 with iV-phenylmaleimide, dimethyl maleate, diethyl fu-marate, methyl vinyl ketone, dimethyl acetylenedicarboxylate, and 1,4-naphthoquinone adducts 92 (mp 227-228°C, 75%), 93 (mp 120-121°C, 65%), 94 (mp 129-130°C, 51%), 95 (mp 81-82 C, 23% an unidentified product was also isolated), 96 (mp 149-150°C, 62%) and 97 (mp 315-316°C, 19%) were obtained. l-Phenylbenzo[c]furan is assumed to be an intermediate in these reactions. Whereas the formation of 92-96 can be simply... 

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