2-hydroxyaldehydes

3-Dichloro-5,6-dicyanobenzoquinone has been employed to oxidise 4-methylphenol stirred in methanolic solution at ambient temperature over 1.5 to 2 hours to give an 84% yield of 4-hydroxybenzaldehyde (ref.9). This is an all- 

In an interesting modification of the Reimer-Tiemann reaction the dropwise addition of chloroform to a mixture of phenol and a-cyclodextrin in 10% aqueous sodium hydroxide at OO C and reaction over 10 hours afforded 4-hydroxybenzaldehyde in 46% yield (ref. 10). Both these methods are shown below 

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GattermaDD synthesis A method for the synthesis of aromatic hydroxyaldehydes. E.g. AICI3 is used to bring about the condensation of phenol with a mixture of gaseous hydrochloric acid and hydrocyanic acid an aldimine hydrochloride is formed and on hydrolysis gives p-hydroxybenzaldehyde... 

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

Racemic pantolactone is prepared easily by reacting isobutyraldehyde (15) with formaldehyde ia the presence of a base to yield the iatermediate hydroxyaldehyde (16). Hydrogen cyanide addition affords the hydroxy cyanohydria (17). Acid-cataly2ed hydrolysis and cyclization of the cyanohydria (17) gives (R,3)-pantolactone (18) ia 90% yield (18). 

The TK-catalyzed reaction requires the presence of thiamine pyrophosphate and Mg " as cofactors. Although the substrate specificity of the enzyme has not been thoroughly investigated, it has been shown that the enzyme accepts a wide variety of 2-hydroxyaldehydes including D-glyceraldehyde 3-phosphate [591-57-1], D-glyceraldehyde [453-17-8], D-ribose 5-phosphate /47(9(9-2%/7, D-erythrose 4-phosphate and D-erythrose [583-50-6] (139,149—151). 

C=N, C=S, C=C, and N N containing substrates. Thus oxa2oles, imidazoles, thiazoles, p rrroles, and 1,2,4-triazoles have been prepared, respectively. Furthermore, p-tolylsulfonylmethyl isocyanide has found use in a one-step conversion of ketones into cyan-idea and in a two-step synthesis of a-hydroxyaldehydes from ketones. ... 

Patemo-Biichi reaction between 2-methylfuran 31 and an a-hydroxyaldehyde 30 to form the core oxetane. Two of the three stereocenters set in the electrocyclization appear in the final product while the third is selectively reversed with anomeric assistance. 

The limitations of the reaction consist in the nonavailability of suitably substituted 2-buten-l-ones (78), in the moderate yields (usually up to 40%) and poor purity of the products, and in the fact that in most cases at least three substituents are required in positions 2, 4, and 6 of the resulting pyrylium salt for its isolation. Ethylidene-acetone (78, R = Me, R = H) and crotonaldehyde (78, R = H, R =Me) failed to yield pyrylium salts on acetylation with AcCl-I-AlClg however, acetylation with AC2O+HCIO4 of jS-hydroxyaldehyde... 

A variety of 1,3-oxazolidines have been used as chiral formyl anion equivalents for addition to aldehydes. Thus, for example, reaction of N-protected norephedrine with Bu3Sn-CH(OEt)2 gives 48, and transmetallation with BuLi followed by addition of benzaldehyde affords the expected adduct 49. The selectivity at the newly formed alcohol center is poor, but the situation can be salvaged by oxidation and re-reduction, which affords the product 50 with >95% d.e. It is then a simple matter to hydrolyze off the oxazolidine, although the resulting hydroxyaldehydes... 

The (racemic) tmns disulfoxide of 1,3-dithiolane 59 is readily deprotonated at C2 by lithium hexamethyldisilazide, and the resulting anion reacts with aldehydes at -78°C with moderate to excellent diastereoselectivity to give mainly the products 60, although subsequent cleavage of these to give the a-hydroxyaldehydes was not described (97JOC1139). 

In the Webb and Levy test (60) for 2-deoxy pentoses, the same hydroxyaldehyde intermediate (4) (30), formed by treating the sugars with trichloracetic acid, reacts with p-nitrophenylhydrazine to yield the pyridazinium salt (5) from which a quinonoid dye (6) absorbing at 560 m/i, is formed in alkaline medium. 

However, the free hydroxyaldehyde and tetra-2-propenylzirconium lead predominantly, in an intramolecular allyl transfer, to the product of formal chelation control87. 

The natural acceptor aldehyde can be considerably varied among phosphorylated as well as unphosphorylated hydroxyaldehydes, which are both converted at comparable rates (Table 5)13-44 47. Although the catalytic reaction creates only a single stereocenter, the enzymes from yeast or spinach efficiently distinguish between adjacent configurations with preference for (3SAR)-i>yn isomeric ketose products44 47, which nicely parallel those derived from FruA reactions (Section 1.3.4.6.1). 

The high stereoselectivity of the transketolase reaction also enables the resolution of racemic a-hydroxyaldehydes23,26. Treatment of racemic 2-hydroxyaldehydes and hydroxypyruvic acid with transketolase, gave the corresponding L-2-hydroxyaldehydes that are not substrates for the enzyme and, therefore, remained unreacted. The corresponding D-enantiomers were consumed and gave the condensation products. 

Dithioacetal monoxide anions react with carbonyl compounds in a similar way affording the corresponding a-hydroxy aldehyde dithioacetal oxides 428. Ogura and Tsuchihashi, who performed this reaction for the first time using the anion of methyl methylthiomethyl sulphoxide 324, obtained in this way a series of a-hydroxyaldehydes 429504 (equation 257). 

Hydroperoxides, as optically active oxidizing agents 289-291 Hydrosulphonylation 172 /J-Hydroxyacids 619 a-Hydroxyaldehydes, synthesis of 330 a-Hydroxyalkyl acrylates, chiral 329 j -Hydroxycarboxylic esters, chiral 329 3-Hydroxycycloalkenes, synthesis of 313 Hydroxycyclopentenones, synthesis of 310 -Hydroxyesters 619 synthesis of 616 Hydroxyketones 619, 636 Hydroxymethylation 767 a-Hydroxysulphones, synthesis of 176 / -Hydroxysulphones 638, 639 reactions of 637, 944 electrochemical 1036 synthesis of 636 y-Hydroxysulphones 627 synthesis of 783... 

Figure 10.17 Kinetic enantiopreference of class II DHAP aldolases useful for racemic resolution of a-hydroxyaldehydes.

Figure 10.24 Diastereoselectivity in FruA catalyzed aldol additions to 3-hydroxyaldehydes under thermodynamic control, and synthesis of L-fucose derivatives based on thermodynamic preference.

Figure 10.26 Short enzymatic synthesis of L-fucose and hydrophobic analogs, and of L-rhamnose, by aldolization-ketol isomerization, including kinetic resolution of racemic hydroxyaldehyde precursors.

Aldehydes up to a chain length of four nonhydrogen atoms are tolerated as acceptors. 2-Hydroxyaldehydes are relatively good acceptors, and the D-isomers are preferred over the t-isomers [180]. Reactions that lead to thermodynamically unfavorable structures may proceed with low stereoselectivity at the reaction center [181]. Recently, a single-point mutant aldolase was found 2.5 times more effective than the wild type in accepting unphosphorylated glyceraldehyde [182,183]. 

In 1919, he resumed his position as assistant in the Berlin Institute and, in 1920, obtained his Habilitation with a thesis on the ring-chain tautomer-ism of y- and 5-hydroxyaldehydes. In 1922, Helferich was called to the position of Departmental Head at the Kaiser Wilhelm Institute for Fibre Chemistry in Berlin-Dahlem. However, he never actually occupied this position, for, in the autumn of that year, he accepted a personal chair in organic chemistry at the University of Frankfurt in the Institute headed by Julius von Braun. 

In his first independent work, Helferich prepared y-hydroxyvaleral-dehyde (4-hydroxypentanal) by reduction and ozonolysis of methylhep-tenone, readily available from citral by a retro-aldol reaction. He was able to show that, similarly to the saccharides, this hydroxyaldehyde exists in... 

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