Quinoxaline-2-carboxaldehydes

Quinoxaline-2-carboxaldehydes are conveniently prepared either from the corresponding methyl- or polyhydroxyalkylquinoxalines. The oxidation of methylquinoxalines to quinoxalinecarboxaldehydes is usually carried out with selenium dioxide, and sodium metaperiodate (NaI04) is the reagent recommended for the oxidation of tetrahydroxybutyl-quinoxalines. An indirect method for the conversion of methylquinoxalines into quinoxalinecarboxaldehydes is illustrated in Scheme 1. 

Quinoxaline on treatment with trioxane, hydrogen peroxide, and ferrous sulfate in acid solution yields 2-trioxanylquinoxaline (1), and this on acid hydrolysis gives quinoxaline-2-carboxaldehyde in an overall yield of 17% (Scheme 2). ... 

Quinoxaline-2-carboxaldehyde has been converted into the 2-carboxylic acid by oxidation with potassium permanganate in acetone and reduced to the 2-hydroxymethyl compound by treatment with formalin and potassium hydroxide. It also undergoes other typical reactions of aromatic aldehydes such as benzoin formation on reaction with potassium cyanide - and condensation reactions with malonic acid and its diethyl ester and Schiff base formation. Acid-catalyzed reaction of quinoxaline-2-carboxaldehyde with ethylene glycol gives the cyclic acetal the diethylacetal has been prepared by reaction of 2-dibromomethylquinoxaline with sodium ethoxide. " An indirect preparation of the oxime 11 is achieved by treatment of 2-nitromethyl-quinoxaline (10) with diazomethane followed by thermolysis of the resulting nitronic ester. 

An interesting property of quinoxaline-2-carboxaldehyde phenyl-hydrazone (12) is its ability to undergo intramolecular cydization to the pyrazoloquinoxaline 13. A series of arylhydrazones (15) have been... 

Quinoxaline-2-carboxaldehyde thiosemicarbazones have been screened for antitubercular and antitumour activity but failed to show significant activity. 

Diazomethane methylation of quinoxaline-2-carboxaldehyde yields 2-acetylquinoxaline in excellent yield,and a number of 2-benzoyl-quinoxalines have been prepared by chromium trioxide oxidation of the corresponding 2-benzylquinoxalines Reaction of the quinoxaline ester 2 with acetone and sodium hydride yields the acetoacetylquinoxaline 3 in excellent yield. ... 

Selenium dioxide oxidation of 2-methylquinoxaline yields quinoxaline-2-carboxaldehyde, and 3-methylquinoxaline-2-carboxaldehyde has been similarly prepared from 2,3-dimethylquinoxaline. Dimethylsulfoxide oxidation of 2,3-bis(bromomethyl)quinoxaline yields the furoquinoxaline 45, and this on sublimation gives quinoxaline-2,3-dicarboxaldehyde. 3-Dibromomethylquinoxaline-2-carboxaldehyde (46) is a by-product of the oxidation reaction. Direct selenium dioxide oxidation of 2,3-dimethylquinoxaline appears to be a less satisfactory method of preparing the dialdehyde. ... 

Methods for the synthesis of these hetarylquinoxalines are limited. An option involves the reaction of the 1,2-DAB 5a with 3-hydroxyimino-2-butanone 54 and bromine in a one-pot reaction (Scheme 6.17, Eq. 1) (Sarodnick and Kempter 1983). Another possibility is to react 1,2-DABs 5a-g with quinoxalin-2-carboxylic acid 56, but this synthetic route needs to be performed in a polyphosphoric acid media at 200 °C (Scheme 6.17, Eq. 2) (Mizutani et al. 1994 NoveUino et al. 2005). A third route is to react the 1,2-DAB 5a with quinoxalin-2-carboxaldehyde 58 in benzene at reflux temperamre (Scheme 6.17, Eq. 3) (Lippmann and Shilov 1984). In all three cases, the yield of the target product remains very low. 

Quinoxaline 1,4-dioxide (Quindoxin) has higher antibacterial activity under in vivo than under in vitro conditions. It has been shown that its in vitro activity is enhanced 10 to 100-fold under anaerobic conditions. Derivatives of 3-methylquinoxaline 2-carboxaldehyde 1,4-dioxide such as the N-methylnitrone 86 also have higher in vivo activity than would be expected from in vitro tests. The high in vivo activity of 2,3-dimethyl-quinoxaline 1,4-dioxide is due to the formation of active metabolites, the mono- and dihydroxymethyl derivatives 87 and 88. However the hydroxymethyl derivative of 86 did not show the expected enhanced activity. Compound 88 is referred to in the literature as Dioxidine, and 2,3-bis(acetoxymethyl)quinoxaline 1,4-dioxide is known as Quinoxidine. The trade name for the 2-carboxaldehyde 1,4-dioxide derivative (89) is Car-badox. Of the numerous quinoxaline 1,4-dioxide derivatives patented in... 

The NMR spectrum of the hydrate 3 reveals the presence of two types of methine proton, and this is accounted for by the production of a cis-trans mixture of diols. Alkali treatment of the mono-N-oxide of 2,3-bis(hydroxymethyl)quinoxaline (6) similarly gives the cyclic hemiacetal (7) of 3-hydroxymethylquinoxaline-2-carboxaldehyde. ... 

Promoted by CuI/2-hydroxybenzohydrazide catalytic system, a variety of pyr-rolo[l,2-a]quinoxalines have been efficiently one-pot synthesized from pyrtole-2-carboxaldehyde and 2-haloanilines in moderate to excellent yields (Table 3.8) (Li et al. 2015). 

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