1,4-Naphthoquinone preparation

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. 

The extended quinone 212 was obtained from 2-amino-3-mercapto-1,4-naphthoquinone, prepared in situ, and formaldehyde, with dehydrogenation taking place simultaneously (50JCS680). All attempts to reduce the quinone were unsuccessful. 

Diels-Alder dienophiles a-Acetoxyacrylonitrile. Acetylenedicarboxyhc acid. Acrolein (see 1-o-Nitrophenylbutadiene). Allyl alcohol (see Lithium). 1,4-Benzoquinone (see also 1,4-Naphthoquinone, preparation). /rans-l,2-Dibenzoylethylene. Di-(-butyl azodiformate. Dichloroketene. Dicyanoacetylene. Diethyl acetylenedicarboxylate. 1,4-Dihydronaphthalene-... 

Benzoquinone ( quinone ) is obtained as the end product of the oxidation of aniline by acid dichromate solution. Industrially, the crude product is reduced with sulphur dioxide to hydroquinone, and the latter is oxidised either with dichromate mixture or in very dilute sulphuric acid solution with sodium chlorate in the presence of a little vanadium pentoxide as catalyst. For the preparation in the laboratory, it is best to oxidise the inexpensive hydroquinone with chromic acid or with sodium chlorate in the presence of vanadium pent-oxide. Naphthalene may be converted into 1 4-naphthoquinone by oxidation with chromic acid. 

A fairly general procedure consists in coupling a phenol or naphthol with a diazotised amine, reducing the product to an aminophenol or aminonaphthol, and oxidising the hydroxy compound with acid ferric chloride solution. This method is illustrated by the preparation of (3 (or 1 2)-naphthoquinone ... 

Naphthalenediol. This diol can be prepared by the chemical or catalytic reduction of 1,4-naphthoquinone. Both the diol and quinone are of interest because of their relation to the vitamin K family. Carboxylation of 1,4-naphthalenediol with CO2—K2CO2 followed by neutralization gives... 

Industrially, vitamin is prepared from the chromic acid oxidation of 2-methylnaphthalene (56). Although the yields are low, the process is economical owing to the low cost and availabiUty of the starting material and the oxidizing agent. However, the process is compHcated by the formation of isomeric 6-meth5l-l,4-naphthoquinone. As a result, efforts have been directed to develop process technology to faciUtate the separation of the isomeric naphthoquinone and to improve selectivity of the oxidation. 

A) -Naphthoquinone.—For the best results this preparation must be carried out rapidly. The vessels and reagents required should be made ready in advance. The oxidizing solution is prepared by dissolving 240 g. (0.89 mole) of ferric chloride hexahydrate in a mixture of go cc. of concentrated hydrochloric acid and 200 cc. of water with heating, cooling to room temperature by the addition of 200-300 g. of ice, and filtering the solution by suction. 

The only satisfactory method of preparing /3-naphthoquinone is by the oxidation of 1,2-aminonaphthol in acid solution, and the chief problem involved is that of the preparation of this intermediate in suitable yield and purity. This problem and the literature pertaining to it are discussed elsewhere. Most reports of the preparation of the aminonaphthol include some description of its oxidation, but the only particularly helpful comment on the reaction is that ferric chloride is a better oxidizing agent than chromic acid because at a low temperature it docs not attack the quinone, even when present in excess. ... 

One other method is from 1,2-bromonaphthol through the keto-nitrobromide. Though the parent quinone itself is such a sensitive compound that the material so obtained decomposed within a few hours, the method is of considerable value for the preparation of certain substituted -naphthoquinones. ... 

When just a trace of dark impurity is present, as in some of the commercial preparations, a completely pure product is easily obtained by vacuum distillation, but the ordinary crude reaction product is likely to decompose when treated in this manner. The ether method introduced in the present procedure has the advantage of being simple and efficient. It is equally applicable to the purification of the homologues of a-naphthoquinone. 

Danishefsky et al. succeeded in preparing the benz[a] anthracene core structure 111 of angucycline antibiotics by performing a benzannulation reaction with the cycloalkynone 109 [69]. Deprotonation of the naphthoquinone 110 with DBU yields the desired anthraquinone 111 (Scheme 49). 

It is dangerous to prepare phthalic anhydride because of the oxidation exothermicity and risks of accidental catalysis by rust. This reaction forms naphthoquinone as a by-product. This compound may have caused a large number of accidents (that caused the compounds to ignite spontaneously) causing the compounds to combust. These accidents may have been caus by the naphthoquinone oxidation catalysed by iron phthalates, which are present in this reaction. However, it will be seen later that phthalic anhydride can also decompose in certain conditions that may be combined here. 

Abou-Ouf et al. [16] described a spectrophotometric method for the determination of primaquine phosphate in pharmaceutical preparation. Two color reactions for the analysis of primaquine phosphate dosage form, which are based on 2,6-dichlor-oquinone chlorimide and l,2-naphthoquinone-4-sulfonate, were described. The reactions depend on the presence of active centers in the primaquine molecule. These are the hydrogen atoms at position 5 of the quinoline nucleus and the primary amino group of the side chain. The method was applied to tablets of primaquine phosphate and a combination of primaquine phosphate and amodiaquine hydrochloride. 

The use of the stannylquinones 81 results in the regioselective formation of 1,4-naphthoquinones or 9,10-anthraquinones 82 [40]. Highly-oxygenated angularly-fused polycyclic aromatic compounds are prepared by the ring enlargement [41]. (Scheme 29)... 

Other Quinones.—Look up o-quinones and the three naphthoquinones the best method of preparing a- and / -naphthoquinone is froml 4-andl 2-aminonaphthol respectively, which are obtained from azo-dyes of the two naphthols by reduction (see p. 302). 

The same method described in Procedure 2 (Section 12.1.2) was used for preparative-scale biotransformation of 150 mg of 2-methyl-1,4-naphthoquinone, except that reactions were incubated for only 72 h before being combined, centrifuged, extracted and chromatographically purified to give 50 % yield (92 mg) of product. 

Uses Intermediate for phthalic anhydride, naphthol, 1,4-naphthoquinone, 1,4-dihydro-naphthalene, 1,2,3,4-tetrahydronaphthalene (tetralin), decahydronaphthalene (decalin), 1-nitro-naphthalene, halogenated naphthalenes, naphthol derivatives, dyes, explosives mothballs manufacturing preparation of pesticides, fungicides, detergents and wetting agents, synthetic resins, celluloids, and lubricants synthetic tanning preservative emulsion breakers scintillation counters smokeless powders. 

Most recently, Kiindig has developed some related l,2-di(ferf-amine) catalysts which can be readily prepared from pseudo-enantiomeric quincoridines. These catalysts were shown to be more effective than those disclosed by Oriyama when applied to the ASD of a meso-Caol complex derived from [Cr(CO)3(q -5,8-naphthoquinone)] [188,189],... 

Rueping has further developed this theme by showing that diarylprolinol ether 55 efficiently catalyses the addition of hydroxyquinones to a variety of a,P-unsatu-rated aldehydes as a method for the preparation of both 1,4- and 1,2-naphthoquinones with remarkable levels of enantioselectivity [98],... 

Condensed derivatives have also been prepared. Reaction of 2-aminothi-azoles with 2,3-dichloro-l,4-naphthoquinone yields naphth[2,3-h]im-idazo[2,l-h]thiazole-5,10-dienones 62 via thiazolylaminoquinones 61. Cycli-zation can be effected either with diethylaniline (method a) [77IJC(B)356] or with sodium hydroxide and tetrabutylammonium bromide (TBAB) catalyst (method b) (82H333). Following route b, compound 62 (R = Et) can be isolated in 92% yield. Reactions between 2-aminothiazoles and chloranil leading to dithiazolobenzobisimidazolediones have also been reported [79IJC(B)523]. 

H-l,2,3-Benzodithiazol-6-ones 141 were prepared from p-benzoquinone-4-oximes, S2CI2, N-ethyldi/sopropylamine and NCS (1998T223 Scheme 72). Some ring chlorination occurred and 2,6-substituents were retained in the products except for the ferf-butyl group, which was replaced by chlorine. 1,4-Naphthoquinone 4-oxime and 1,2-naphthoquinone 2-oxime similarly gave dithiazole derivatives 142 and 143 (1998T223). 

Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Since 2000 atovaquone is available as a fixed dose preparation (Malarone) with proguanil for the oral treatment of falciperum malaria. Its activity probably is based on a selective inhibiton of mitochondrial electron transport with consequent inhibition of pyrimidin synthesis. Malarone should not be used to treat severe malaria, when an injectable drug is needed. 

Menaquinone. The incorporation of [2- C]mevalonate and [2- C]-2-methyl-l,4-naphthoquinone into MK-4, normally considered a bacterial quinone, has been demonstrated in marine invertebrates such as crabs and starfish." Incorporation into 2,3-epoxy-MK-4 (163) was also observed. Cell-free extracts have been prepared from Escherichia coli which catalyse the conversion of o-succinylbenzoic acid (164) into l,4-dihydroxy-2-naphthoic acid (165) and menaquinones. In the presence of farnesyl pyrophosphate the major menaquinone produced was MK-3. Genetic studies with mutants of E. coli K12 that require (164) offer support for the generally accepted pathway for MK biosynthesis via (164) and (165)." The enzyme system that catalyses the attachment of the polyprenyl side-chain to 1,4-dihydroxy-2-naphthoic acid to form demethylmenaquinone-9 (166) has been isolated from E. colU ... 

Salama and Omar have described a rapid, specific, and convenient colorimetric method for the determination of procaine hydrochloride in pharmaceutical preparations [40]. The method is based on an intensity measurement of the orange-red color developed when the drug is allowed to react with l,2-naphthoquinone-4-sulfonic acid (sodium salt) in an aqueous solution. The method is suited for routine analysis of official preparations of procaine. 

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