2- Hydroxy-1,4-naphthoquinone reactions

As thiazoles have significant aromatic character, they display poor reactivity in cycloaddition reactions. However, a theoretical study of the Diels-Alder reactions of a thiazole o-quinodimethane 83 with 2- and 3-bromo-5-hydroxy-naphthoquinones 84 and 85 has been carried out (Scheme 24) <2000T1701>. The findings from the PM3, molecular hardness, and ab initio (3-2 Gp) calculations of this study agree with the experimental results and support the statement that hydrogen bonding plays a crucial role on the regiocontrol of the cycloadditions. 

To illustrate how we may now calculate more precisely to what extent a given organic compound may be reduced or oxidized in a given system,.we consider a dilute solution (e.g., 0.1 mM) of 2-hydroxy naphthoquinone [trivial name lawson (LAW), reaction 13 in Table 5] in 5 mAf aqueous hydrogen sulfide at various pH values. As we will see later, since such quinoid compounds undergo reversible redox reactions in natural systems, they may play a pivotal role in the transformation of organic pollutants. Hence, we consider the reversible reaction... 

Malamidou-Xenikaki E, Spyroudis S, Tsanakopoulou M. Studies on the reactivity of aryliodonium ylides of 2-hydroxy-l,4-naphthoquinone reactions with amines. J. Org. Chem. 2003 68 5627-5631. 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Turning from the intramolecular process to the intermolecular ones, we now extend our comparison of the thermal and cation-radical cyclizations. It is also interesting to take sonication into account as a route to initiate cyclizations. The reaction between 2-butenal A,A-dimethylhydrazone (a diene) and 5-hydroxy-l,4-naphthoquinone (a dienophile) gives such an opportunity. In toluene, at 20°C, the reaction follows as depicted in Scheme 7.28 (Nebois et al. 1996). 

When these cycloaddition reactions are carried out with alkynes, furan derivatives are formed. lodonium ylide 5, for instance, on photochemical reaction with alkynes 43, gives benzofurans 44 (86JOC3453) (Eq. 19). In a similar way, the iodonium ylide derived from 2-hydroxy-1,4-naphthoquinone undergoes a cycloaddition reaction with phenylacety-lene to yield benzofuran 45 (Scheme 16) (89LA167). 

This enzyme [EC 1.14.99.27] catalyzes the reaction of 5-hydroxy-l,4-naphthoquinone with AH2 and dioxygen to produce 3,5-dihydroxy-l,4-naphthoquinone, A, and water. The enzyme can also use 1,4-naph-thoquinone, naphthazarin, and 2-chloro-l,4-naphthoquinone as substrates, but not other related compounds. 

Vitamin-K-epoxide reductase (warfarin-insensitive) [EC 1.1.4.2] catalyzes the reaction of 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone with oxidized dithiothreitol and water to produce 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-l,4-naphthoquinone and 1,4-dithiothreitol. In the reverse reaction, vitamin K 2,3-epoxide is reduced to 3-hydroxy- (and 2-hydroxy-) vitamin K by 1,4-dithioerythritol (which is oxidized to the disulfide). The enzyme is not inhibited by warfarin. 

The solid state photochemical reaction of indole with 1,4-naphthoquinone yielded 5H-dinaphtho(2,3-a 2, 3 -c)carbazole-6,ll,12,17-tetrone in addition to 2-(3-indolyl)-1,4-naphthoquinone which was also the only product in the solution photoreaction. Solventless thermochemical reactions of indole with phenanthrenequinone in the presence or absence of zinc chloride gave 10-(lH-indol-3-yl)-9-phenanthrenol and 9,10-dihydro-9-(lH-indol-3-yl)-10-(3H-indol-3-ylidene)-9-phenanthrenol or 10,10-di-lH-indol-3-yl-9(10H)-phenanthrenone, respectively. All of these products were only obtained in trace amounts in corresponding solution reactions, and are different from the adduct 10-hydroxy-10-(lH-indol-3-yl)-9(10H)-phenanthrenone obtained in the solution photoreaction (Wang et al., 1998). 

Addition of water to quinones. The yields of the known Michael addition of water or an alcohol to a 1,4-naphthoquinone such as 5,8-dimethoxy-l,4-naphtho-qninonc arc improved by addition of an oxidant such as Fe2(S04)3 to convert the initial 2-hydroxynuphlhohydroquinone to the corresponding quinone. The presence til ll 1 rcc pert-hydroxy group interferes with the reaction. 

Lau and Gompf359 prepared a series of 2-amino-6-hydroxybenzo[d]-thiazoles and corresponding naphtho[l,2-d]thiazoles on treating 1,4-benzoquinone and 1,4-naphthoquinone with thiourea in acidic media at room temperature. At high temperature the products of the reaction with 1,4-benzoquinone are 5-hydroxy benz[d]-l,3-oxathiol-2-ones... 

Naphthoquinone 1-oxime (772) reacts with aminoguanidine (773) and similar compounds to give 2-aminonaphtho[ 1,2-e][1,2,4]triazine 1-oxides (774). 1-Hydroxy-naphtho[l,2-e][l,2,4]triazin-2-ones can be prepared in an analogous reaction <78HC(33)189, p. 728). 

Bcnzofuran-4,7-dioncs have been synthesized regioselectively by [3 + 2] photoaddition of 2-hydroxy-1,4-benzoquinones with a range of alkenes (equation 185)664. The reaction occurs in 30-60% yield and is a useful method for the synthesis of the benzofuran ring system, which is important in natural products like acamelin665. Substituted naphthoquinones may also be used in this reaction666,667 and this has lead to a very simple two-step synthesis of maturinone. In a similar reaction, a [3 + 2] photoaddition reaction of 2-amino-1,4-naphthoquinones with electron-rich alkenes gave 13-82% yields of 2,3-dihydro-177-bcn/ /]indole-4,9-diones in a single-step process which involved photolysis followed by oxidation (equation 186)668,669. 

Acylated indoles, in their enol form (54), are formed by heating the phenyliodo-nium ylide of 2-hydroxy-1,4-naphthoquinone in the presence of some indoles.58 The intermediacy of an o ,a ,-dioxoketene (55) is suggested. The same reactants (with the exception of indole itself) form 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a Cu(II)-catalysed reaction. 

Photolysis of 5-methyl-1,4-naphthoquinone (24) gives 4-hydroxy-5-methyli-dene naphthalen-1 (5//)-one (25) in the ground state within 2 ps of excitation, with a quantum yield of 1.0.59 Formally, this is a photoenolization reaction however, the product of the reaction also has quinone methide functionality,... 

The Williamson synthesis, using a sodium phenoxide and allyl bromide in methanol solution, is more rapid than the procedure using acetone and potassium carbonate and gives good results.16-36 441 66 Aqueous acetone also has been used as the reaction medium with allyl bromide and sodium hydroxide this method likewise is rapid and sometimes leads to better yields than the procedure using potassium carbonate and acetone.34 Allylation of 2-hydroxy-l,4-naphthoquinone has been carried out by treating the silver salt, in benzene, with allyl bromide 84 some C-alkylation as well as O-alkylation was observed. 

Mn(OAc)3-promoted oxidative reaction of 2-hydroxy-1,4-naphthoquinone (280) with a p-enamino carbonyl compound generates a spiro-lactam (281) as shown in eq. 3.115. 

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. 

Quinoline derivatives (60) have been synthesized by the reaction of 5-alkyl-l,3,4-thia-diazol/oxadiazol-2-thiols with 7-chloro-6-uoro-2,4-dimethylquinoline and by the reaction of 2-hydroxy-l,4-naphthoquinone with 2-chloro-3-formyl-4-methyl/ 6-methyl/7-methyl/8-methylquinolines, respectively, on basic alumina using micro-waves (Kidwai et al., 2000). 

Thermal decomposition of phenyliodonium ylide of 2-hydroxy-l,4-naphthoquinone (lawsone) 403 in the presence of indole derivatives 402 (GH2CI2, reflux, 4-7 h) affords 3-acylated indoles existing in their enol forms 404, through a ring contraction and ot,ot -dioxoketene formation reaction (Scheme 87) <2005JOC8780>. 

The same reactants afford 3-(3-indolyl)-2-hydroxy-l,4-naphthoquinones 405 in a copper-catalyzed reaction (CH2CI2, 00(0+3803)2, rt, overnight). In case the more electron-rich position 3 in the indole ring is substituted, as in 3-methylindole, the reaction takes place from position 2, but the yield of the corresponding derivative is very low (7%) (Equation 95). The thermal reaction of reagent 403 with 1-methylpyrrole afforded the expected acylation product 407 in high yield (Equation 96) <2005J008780>. 

Syntheses of several derivatives of 307 are described, usually in connection with structural elucidation of some natural products (72JCS(P 1)380 75JCS(P1)1936). The parent compound (307) was obtained from 2-chloro-propyl-3-hydroxy-1,4-naphthoquinone after treatment with base (50JA5419). Derivatives of this system were also prepared in Michael reactions between... 

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