Glyoxal derivatives

The isomer of isoproterenol in which both aromatic hydroxyl groups are situated meta to the side chain also exhibits bron-chiodilating activity. Oxidation of 3,5-dimethoxyacetophenone by means of selenium dioxide affords the glyoxal derivative (15). Treatment of the aldehyde with isopropylamine in the presence of... 

Table 4.9 Diels-Alder reactions of glyoxal derivatives promoted by microwaves under different experimental conditions...

The ability to direct conjugation or modification specifically through arginine residues using this chemistry has been exploited in the availability of the only photoreactive glyoxal derivative, APG. 

Oxidation of methyl ketone guanylhydrazones (686) with selenium dioxide affords the corresponding monosubstituted glyoxal derivatives (687) which cyclize to the 5-unsubstituted 3-amino-1,2,4-triazines (473) (78HC(33)189, p.360). We have already noted the cyclization of bis(alkylidene)- or bis(arylidene)-acetone guanylhydrazones (475) in the synthesis of 6-(vinyl-substituted) 3-amino-1,2,4-triazines (477) (Section 2.19.4.1.1). 

Methyl glyoxylate and ( )-3-hexenol produce the acctoxyalkoxyacetic acid ester 4 in a two-step sequence. Cyclization of the glyoxal derivative 4 in the presence of tin(IV) chloride gave the tetrahydropyranylcarboxylate 5 in 83% yield after 6-endo reaction and chloride ion attack27. Tetrahydropyran 5 shows defined relative stereochemistry at all three asymmetric carbon centers. 

With diazadienes derived from aromatic amines the dimer specificity can be raised to 95-99% while with diazadienes from (lR,3R,4.S )-4-menthan-3-amme up to 24% ee of (S -vinylcyclo-hexcne (glyoxal derivative) or 30 % ee of (S)-4-vinylcyclohexene (2-acetylpyridine derivative) are obtained. Higher asymmetric inductions (up to 62% ee) are obtained with diazadienes of the type pyridyl-CH=N-menthyl and 8-substituted derivatives 4 thereof61. 

Condensation of 1 with glyoxal derivatives or 1,3-dichloroacetone gave the Ws(dimedonyl)methane 40 whose fusion with an equimolar amount of ammonium acetate or heating with primary amines in chlorobenzene gave 4,5,6,7-tetrahydroindole 41 (89IJC(B)326). Reaction of 41 (R1 = Ph) with diazomethane or amino-alkylchloride afforded ethers 42, and with hydrazine gave the disubstituted hydrazine 43 as the major product and the indole derivative 44 as a minor one (89IJC(B)326) (Scheme 6). 

Many oxazoles react slowly at room temperature with 2,4-dinitrophenyl-hydrazine in hydrochloric acid to form hydrazones (223) by ring fission.84 160 On the other hand, refluxing results in the formation of osazones (224) of glyoxal derivatives, presumably via 223.877... 

This reaction is, however, only of preparative use if the glyoxal derivative is itself obtained in a reaction carried out in alkaline solution, i.e., in the same batch. An example of this is provided by the preparation of p-bromomandelic acid from / ,co,eo-tribromoacetophenone recorded in Organic Syntheses 42... 

Bailey et al. (1965) found that in a-diazocarbonyl compounds with a terminal diazo group (-CH=N2) the diazo function is replaced by an O-atom, i.e., a glyoxal derivative is formed primarily, but the final products result from CH bond cleavage. In other cases, however, the a,yff-dicarbonyl compound is stable. An example, described by Ursini et al. (1992), is the oxo-de-diazoniation (9-35) of various 6-diazopenicillanates (9.70, R = 4-NO2C6H4CH2 and other alkyl groups). The a-diketone is obtained at -15 to -10°C in dichloromethane with ozone in 86-97% yield. 

A direct catalytic asymmetric aldol-type reaction of 3-substituted-2-oxindoles with glyoxal derivatives was catalyzed by a similar chiral )V,A -dioxide-Sc(OTf)3 complex (eq 33). The complex efficiently catalyzed the aldol reaction affording the 3-(a-hydroxy-/3-carbonyl) oxindoles with vicinal quaternary-tertiary stereocenters, in up to 93% yield, 99 1 dr, and >99% ee under mild conditions. 

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