Aldehydes Anthraquinone

Addition of sodium dithionite to formaldehyde yields the sodium salt of hydroxymethanesulfinic acid [79-25-4] H0CH2S02Na, which retains the useful reducing character of the sodium dithionite although somewhat attenuated in reactivity. The most important organic chemistry of sodium dithionite involves its use in reducing dyes, eg, anthraquinone vat dyes, sulfur dyes, and indigo, to their soluble leuco forms (see Dyes, anthraquinone). Dithionite can reduce various chromophores that are not reduced by sulfite. Dithionite can be used for the reduction of aldehydes and ketones to alcohols (348). Quantitative studies have been made of the reduction potential of dithionite as a function of pH and the concentration of other salts (349,350). 

The methyl substituent of 2-methyl-4,8-dihydrobenzo[l,2- 5,4-. ]dithiophene-4,8-dione 118 undergoes a number of synthetic transformations (Scheme 8), and is therefore a key intermediate for the preparation of a range of anthraquinone derivatives <1999BMC1025>. Thus, oxidation of 118 with chromium trioxide in acetic anhydride at low temperatures affords the diacetate intermediate 119 which is hydrolyzed with dilute sulfuric acid to yield the aldehyde 120. Direct oxidation of 118 to the carboxylic acid 121 proceeded in very low yield however, it can be produced efficiently by oxidation of aldehyde 120 using silver nitrate in dioxane. Reduction of aldehyde 120 with sodium borohydride in methanol gives a 90% yield of 2-hydroxymethyl derivative 122 which reacts with acetyl chloride or thionyl chloride to produce the 2-acetoxymethyl- and 2-chloromethyl-4,8-dihydrobenzo[l,2-A5,4-3 ]-dithiophene-4,8-diones 123 and 124, respectively. 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

Aliphatic aldehydes and ketones and also aliphatic-aromatic ketones can be converted into the corresponding hydrocarbons alkyl-phenols can be obtained from phenolic-aldehydes and -ketones p-hydroxy-benzophenone yields p-benzylphenol benzoin and benzil yield dibenzyl anthraquinone yields anthracene dihydride. 

Anthrimides and Other Linked Anthraquinones. Among the anthrimides (dia-nthraquinonyl-amines), only the a,(3 derivatives have achieved limited importance as vat dyes. Coupling two anthraquinone molecules via functional derivatives of the 2-aldehyde (or 2-carboxy) group offers another type of building block for vat dyes. Such compounds, e.g., 1-aminoanthraquinones, are linked in the 2-position via an azine or oxadiazole group, and all have good fastness. 

Anthraquinone synthesis.1 The original anthraquinone synthesis (10, 75) from benzamides and benzaldehydes involving a tandem orf/io-lithiation can be improved by use of an ort/to-bromobenzaldehyde as the second component. In this version, the second lithiation involves halogen-metal exchange, which results in higher yields. In the example cited here, the yield was only 15% in the absence of the bromine substituent on the aldehyde. 

Hydroxymethylation of anthraquinones (Marschalk reaction). Krohn1 has reviewed this reaction, particularly for the synthesis of anthracyclinones. It is particularly useful for preparation of optically active rhodomycinones by use of chiral aldehydes (166 references). 

The key intermediate in the total synthesis of furaquinocin was obtained in good yield by a reductive Heck reaction that proceeded with a sterically hindered base pentamethylpiperidine (PMP) <02JA11616>. A new hypothesis for the major skeletal rearrangement (anthraquinone —> xanthone —> coumarin) that occurs in the complex biosynthesis of aflatoxin Bi was proposed. To test this hypothesis, an intermediate 11-hydroxy-O-methylstergmatocystin (HOMST) was synthesized as shown below. The key transformation in this synthesis involved the treatment of an ester-aldehyde with Pr3SiOTf, which smoothly produced a mixed acetal. Direct reduction with DIBAL-H led to the aldehyde. The desired product was eventually obtained via several steps as shown <02JA5294>. 

The linking groups of the ALS molecules, cholesteryl 4-(2-anthryloxy)buta-noate (CAB) and cholesteryl anthraquinone-2-carboxyIate (CAQ), allow them to adopt an overall rodlike shape. (See Structure 4.) CAB forms gels with hydrocarbons, alcohols, aldehydes, esters, amines, etc. (Table l) [76[, and both CAB and CAQ gel more complex fluids, like silicone oils [77[. Many CAB gels are luminescent and some are metastable, exhibiting a gel-to-liquid/solid phase separation after various periods of time. 

Intramolecular Marschalk reaction. Ai. intramolecular Marschalk reaction (9, 376) can be used to effect a synthesis of anthracvclinones from anthraquinones. Thus the oi-hydroxy aldehyde 2, formed on saponification of the a-hydroxydichloride 1, on reduction of the quinone group cyclizes in the alkaline medium to the tetracyclic tran.s- and ci/j-diols(3and4)inaboutequal amounts. Cyclization underphase-transfer conditions results in improved yields and, more importantly, can alter the stereoselectivity. Triton B is the most effective catalyst for stereoselective cyclization to the desired natural tran -diol. 

Electrophilic reactions on the electron-deficient anthraquinone are normally not possible. However, in 1936 Marschalk described the facile alkylation of the anthraquinone nucleus by aldehydes after reduction of the quinone to the electron-rich hydroquinone using dithionite [34]. This strategy might be called a redox Umpolung , since the chemical reactivity of the anthracene core is reversed by the redox reaction. 

It has been reported that several transition metal complexes catalyze the hetero-Diels-Alder reaction between a variety of aldehydes, in particular benzaldehyde, and Danishefsky s diene (Sch. 52). With the [CpRu(CHIRAPHOS)] complex the ee is modest (25 %) (entry 1) [192]. The chiral complex VO(HFBC)2 performs better in this reaction (entry 2) [193]. In experiments directed towards the synthesis of anthra-cyclones, this complex was used in cycloadditions between anthraquinone aldehydes with silyloxy dienes. One example is shown in Sch. 53 [194]. Compared with the chiral aluminum catalyst developed earlier by Yamamoto and co-workers [195], the vanadium catalyst results in lower enantioselectivity but has advantages such as ease of preparation, high solubility, stability towards air and moisture, and selective binding to an aldehyde carbonyl oxygen in the presence of others Lewis-basic coordination sites on the substrate. 

Much effort has been devoted to functionalization of anthraquinone spacers. Thus, the Knoevenagel condensation of aldehydes 932 and 933 with malononitrile using ammonium nitrate gave the Jt-exTTF derivatives 934 and 935 in 65-82% yields (Equation 103) <1998T11651>. The aldehyde 933 was also utilized in syntheses of new jt-exTTFs containing oligomeric spacers <2002T7463>. 

Air, the cheapest oxidant, is used only rarely without irradiation and without catalysts. Examples of oxidations by air alone are the conversion of aldehydes into carboxylic acids (autoxidation) and the oxidation of acyl-oins to a-diketones. Usually, exposure to light, irradiation with ultraviolet light, or catalysts are needed. Under such circumstances, dehydrogenative coupling in benzylic positions takes place at very mild conditions [7]. In the presence of catalysts, terminal acetylenes are coupled to give diacetylenes [2], and anthracene is oxidized to anthraquinone [3]. Alcohols are converted into aldehydes or ketones with limited amounts of air [4, 5, 6, 7], Air oxidizes esters to keto esters [3], thiols to disulfides [9], and sulfoxides to sulfones [10. In the presence of mercuric bromide and under irradiation, methylene groups in allylic and benzylic positions are oxidized to carbonyls [11]. 

Electrochemical methoxylations usually lead to acetals or ketals these must be distilled and/or hydrolzed [8] to give the target molecules. The resulting ketones or aldehydes are purified again. In the anthraquinone process of Hydro Quebec [9], some of the cru-denaphthoquinone is purified further, but most of the crude products is reacted with butadiene to yield tetrahydroanthraquinone, which is dehydrogenated to anthraquinone. 

Hou, Y., Wan, P., Formal Intramolecular Photoredox Chemistry of Anthraquinones in Aqueous Solution Photodeprotection for Alcohols, Aldehydes and Ketones, Photochem. Photobiol. Sci. 2008, 7, 588 596. 

Selective reductions. Brown et al.2 conducted an extensive study of reductions with diborane in THF. Most aldehydes and ketones are readily reduced unusually high stereoselectivity was realized in the case of norcamphor, which was reduced to 98% endo-norbornanol and 2% exo-norbornanol. p-Benzoquinone is reduced to hydroquinone at a moderate rate, but reduction of anthraquinone is sluggish. Carboxylic acids are reduced very rapidly indeed this group can be reduced selectively in the presence of many other substituents. Acid chlorides react much more slowly than carboxylic acids. Esters and ketones are reduced relatively slowly. Reactions with epoxides are relatively slow and complex. 

The photoreduction efficiency of carbonyl compounds such as 9,10-anthraquinone, 1,4-anthraquinone, 6,13-pentacenequinone, and 2-phenyl-9.10-anthraquinone, in the presence of anthracene, pyrene, naphthalene, biphenyl, 1,4-benzoquinone, and 1,4-naphthoqulnone has been shown to depend on the relative positions and nature of the electronic levels of the substrate and acceptor. Photoreduction of aromatic ketones to alcohols or pinacols can be catalysed by CdS powders using triethylamine as sacrificial donor in MeCN, and morphology is reported by the same authors to affect the two-electron transfer photoreductions of aromatic ketones on CdS induced by visible llghti under analogous conditions olefins behave similarly. Aldehydes of the type RCHO (R -jB -tolyl, g-anlsyl, hexyl) have been photoreduced to the corresp>onding... 

Allylic oxidation, for example, of cyclohexene to 2-cyclohexenone, and oxidative cleavage of styrene to benzaldehyde are readily accomplished with oxygen such reaction systems contain ALhydrox3fphthalimide and l,4-diamino-2,3-dichloro-9,10-anthraquinone. Aldehydes are converted into carboxylic acids with Pd/C, KOH and catalytic amounts of NaBH4 in the air. Very similar conditions (K2CO3 instead of KOH) are described for oxidation of benzylic and allylic alcohols. ... 

Kuo et al., [18] investigated the structure-activity relationships of anthraquinones on intestinal motility, using rabbit small intestinal strips. This study revealed the critical requirement of a hydroxy group at 2 position, whereas the presence of other polar groups at this position, such as an amino, aldehyde and carboxylic acid groups, significantly reduced the activity. The presence of a methyl group and esterification of the carboxylic acid at 2 position was found to abolish the activity. 

In the tricyclic anthraquinone series, 1,4-dihydroxy-9,10-anthraquinone in the leoco form undergoes aldol addition with an aldehyde followed by loss of water from the aldol intermediate and isomerisation to give the 2-alkyl derivative depicted (ref.58,59). 

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