Aromatic hydroxyaldehyde

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... 

Keywords aromatic hydroxyaldehyde, ethyl malonate, methyl malonate, Knoe-venagel reaction, microwave irradiation, 3-substituted coumarin... 

The synthetic utility of the methods described above is even more if it is realised that the lithiation reaction, being subject to orientation rules mentioned earlier, can provide aromatic hydroxyaldehydes which are not readily available by other acid catalysed methods. These are illustrated by the following examples . ... 

Fiege, H., Wedemeyer, K., Bauer, K.A., Krempel, A., Molleken, R.G. Further development of a classical process for the synthesis of aromatic hydroxyaldehydes In Croteau, R., Ed. Fragrance Flavor Subst., Proc. Int. Haarmann Reimer Symp., 2nd 1979 (Pub. 1980), 63, D PS Verlag, Pattensen... 

Schreiber and coworkers reported a branching diversity-oriented synthesis applying DTDA methodology that yielded 29 400 discrete compounds comprising 10 distinct polycyclic skeletons [31]. Scheme 2.20 shows only two DTHDA products in the DTDA reactions in which 40 aromatic hydroxyaldehydes, 41 disubstituted dienophiles, and 22 tri- or tetrasubstituted dienophiles were employed as building blocks. 

Hydroxamic acid gives a strong color with ferric chloride. This reaction is suitable for the detection of aldehydes in the presence of ketones. Aromatic / -hydroxyaldehydes, / -aminobenzaldehyde, vanillin, / -dimethyl-aminobenzaldehyde, salicylaldehyde, and aliphatic aldehydes with a hydroxy group in the y-position do not react. A positive reaction is observed with benzyl ketones in strongly alkaline media. It is necessary, therefore, to keep the mixture distinctly but not excessively alkaline. This reaction can be utilized for the separation of aldehydes from their mixture with ketones by converting the acid to its insoluble copper salt. Paper chromatography can be used for the identification of aldehydes in mixtures (41). 

The values of 3/(NH,H) coupling constant observed for imine proton can be helpful in detection of the proton transfer processes and determination of mole fractions of tautomers in equilibrium. For NH-form, this value is close to 13 Hz, lower values usually indicate the presence of tautomeric equilibrium. It should be mentioned that the values below 2.4 Hz have not been reported. The chemical shift of C—OH (C-2 for imines, derivatives of aromatic ortho-hydroxyaldehydes or C-7 for gossypol derivatives) carbon to some extent can be informative, however, this value depends on type of substituents and should be interpreted with caution. 

Analysis of the NMR data for symmetrical and unsymmetrical di-Schiff bases being derivatives of frans-l,2-diaminocyclohexane and various aromatic orf/zo-hydroxyaldehydes [22] has shown the presence of proton transfer equilibrium.45,46... 

Domination of the S-diastereomers for the dioxovanadium(V) Schiff base complexes being derivatives of aromatic orf/zo-hydroxyaldehydes or ketones and (S)-(+)-2-(aminomethyl)-pyrrolidine [35] was shown and the molar ratio of the diastereomers was determined by means of integration of the H signals.85... 

The pyridinium chlorochromate (PCC) oxidations of pentaamine cobalt(III)-bound and unbound mandelic and lactic acids have been studied and found to proceed at similar rates.Free-energy relationships in the oxidation of aromatic anils by PCC have been studied. Solvent effects in the oxidation of methionine by PCC and pyridinium bromochromate (PBC) have been investigated the reaction leads to the formation of the corresponding sulfoxide and mechanisms have been proposed. The major product of the acid-catalysed oxidation of a range of diols by PBC is the hydroxyaldehyde. The reaction is first order with respect to the diol and exhibits a substantial primary kinetic isotope effect. Proposed acid-dependent and acid-independent mechanisms involve the rapid formation of a chromate ester in a pre-equilibrium step, followed by rate-determining hydride ion transfer via a cyclic intermediate. PBC oxidation of thio acids has been studied. ... 

Hydrogenation of esters, with copper chromite and Raney nickel, 8, 1 Hydrohalogenation, 13, 4 Hydroxyaldehydes, aromatic, 28, 1 a-Hydroxyalkylation of activated olefins, 51, 2... 

Hydroxyaldehydes, with an intervening quaternary centre, have been synthesized enantioselectively by direct aldol reactions of oqa-dialkylaldehydes with aromatic aldehydes, using a chiral bifunctional pyrrolidine sulfonamide organocatalyst.118... 

A 3-hydroxyaldehyde (or ketone) will undergo elimination under basic conditions if the double bond being formed is especially stable, e.g., conjugated with an aromatic system. Such eliminations can occur under the reaction conditions of the base-promoted aldol condensation. An example is the formation of 3-phenyl-2-butenal by an E2 elimination from 3-hydroxy-3-phenylbutanal. 

Asymmetric hydrogenation of either a carbonyl or an imino group to a hydroxyl group or an amino group has frequently been employed for the introduction of chirality in amino acid syntheses. Corey s catecolborane-oxazaborolidine protocol enables transformation of difluoromethyl ketone 1 into alcohol 2 with excellent enantioselectivity. The reaction of diastereoselective amination of a-hydroxyaldehyde 3 with A,A-diallylamine and 2-furyl-boronic acid provides furyl amino alcohol 4 in good chemical yield along with excellent diastereoselectivity. This protocol is applicable for the preparation of amino acids and amino alcohols with a trifluoromethyl group by the combination of /V,/V-diallyl or N,N-dibenzyl amine and aromatic, heteroaromatic and alkenyl boronic acids [7]. The usual chemical transformations as shown in steps 5 to 8 in Scheme 9.1 lead to (2S,3R) difluorothreonine 5 [8]. 

Mannich bases formed from formaldehyde, secondary amines and ort/io-derivatives of phenol and Schiff bases derived from aromatic ort/io-hydroxyaldehydes are treated as rather convenient model systems to study intramolecular proton transfer . 

This list has to be continued by the Dakin rearrangement, which is the oxidation of aromatic ortho- or para-hydroxyaldehydes with H2O2 in the presence of alkali to afford polyhydric phenols (equation 133). 

Tetrabutyl ammonium hydroxide and dimethyl sulfate in dichlo-romethane have been used to methylate a number of aromatic hydroxyacids and hydroxyaldehydes (Ramaswamy et al. 1985). 

The cyanine salt 27 is obtained by treatment of the quinoxalinium perchlorate 26 in pyridine with triethylorthoformate, and as expected the corresponding methylsulfate (28) is found to undergo ready condensation with aromatic aldehydes Reaction of 28 with o-hydroxyaldehydes yields spiropyrans such as 29. " 1-Acetoxyquinoxalinium perchlorates of... 

In a similar vein, bullqr silojqr derivatives of serine and threonine have been found to be hydrophobic enough to furnish the expected adducts with good enantioselectivities. In the presence of tert-butyldimethylsi-lylojy L-threonine (OTBDMS-L-Thr), the aldol reaction between cyclohexanone and benzaldehyde in water was effective with only 2 mol% of the catalyst (yield 58% ee 96%) in favour of the anti-isomer (dr 8 1). This catalyst proved to be remarkably effective with various aromatic aldehydes and the adducts were obtained in excellent yields and nearly perfect ee in water. The anti- or q n-aldol products were obtained respectively from cyclohexanone or TBDMS protected p-hydroxyaldehyde. 

Proline (1) has showed to be a effective catalyst for both the homo-aldol and the cross-aldol reactions (Schane 4.12). Thus, the homo-aldol process using propi-onaldehyde (R =Me in 5a and R =Et in 2) afforded the expected a-hydroxyaldehyde in an excellent enantioselectivity for the major anti-29. Under similar reaction conditions, the cross-aldol reaction between propionaldehyde as source of nucleophile (5, R =Me) and other different aliphatic and aromatic aldehydes has been performed, giving the anti-29 isomer as the main diastereoisomer [71], This reaction course has been explained due to the steric hindrance as well as the kinetic inaccessibility of the hydrogen for some a,a-disubstimted aldehydes which leads, in both cases, to a very thermodynamic unstable corresponding nucleophilic enamine intermediate. 

Morken and coworkers [39b] developed the first asymmetric reductive aldol reaction with silanes as reductants in combination with a chiral rhodium catalyst. a,P-Unsaturated esters were reacted with several aldehydes to provide the corresponding aldol products 79 in good yields and enantio- and diastereoselectivities (Scheme 8.23). Both aliphatic and aromatic aldehydes could be converted into aldol products 79 under these conditions. Furthermore, the group reported an iridium-catalyzed asymmetric version that tolerated various protected hydroxyaldehydes [39aj. On the basis of this precedence, a highly enantio- and diastereoselective... 

This test is based on the fact that cupric ion will oxidize aliphatic aldehydes, including a-hydroxyaldehydes, but not aromatic aldehydes. The reagent used in this test is a solution of cupric sulfate, sodium citrate, and sodium carbonate. The citrate ion forms a complex with the Cu(II) ion so that Cu(OH)2 does not precipitate from the basic solution. A positive test for the presence of the aliphatic aldehyde group in an aldose is evidenced by the formation of a red precipitate of cuprous oxide, CU2O (Eq. 23.5). A yellow precipitate is occasionally observed as a positive test. This yellow solid has not been characterized, but its formation seems to depend on the amount of oxidizing agent present. 

VANADIUM(IV) COMPLEXES DERIVED EROM AROMATIC o-HYDROXYALDEHYDES AND TYROSINE DERIVATIVES CATALYTIC EVALUATION IN SULFOXIDATIONS... 

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