Benzaldehyde, derivatives

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Aldehydes can also be prepared by the carbonylation of aryl and alkenyl halides and triflate, and benzyl and allyl chlorides using tin hydride as a hydride source and Pd(PhjP)4 as a catalyst[377]. Hydrosilancs arc used as another hydride source[378]. The arenediazonium tetralluoroborate 515 is converted into a benzaldehyde derivative rapidly in a good yield by using Et ,SiH or PH MS as the hydride source[379]. 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

In another example reaction of aldehyde 22 and amine 23 gave imine 24 which cyclised under strongly acidic conditions to yield the corresponding isoquinoline 25 in good yields It is interesting that the aldehyde portion 22 is not benzaldehyde derived. 

Other aldehydes which have been used in the reaction are pro-panal, butanal, glycolaldehyde, 3-hydroxybutanal, and a number of phenylacetaldehydeand benzaldehyde derivatives. Whereas condensation of tryptophan with acetaldehyde takes place even at room temperature and pH 6.7, the reactions with chloral, chloroacetaldehyde, and crotonaldehyde fail entirely. 

The aldehyde structures and the tosylhydrazone salts were varied in an extensive study of scope and limitations, with use of both achiral and chiral sulfur ylides [73]. Aromatic aldehydes were excellent substrates in the reaction with benzaldehyde-derived ylides, whereas aliphatic aldehydes gave moderate yields and transxis ratios. 

Lucchi , who studied the oxidation of substituted benzaldehyde derivatives found that chlorine atoms in the meta and para position accelerate the reaction and alkyl groups retard the oxidation. A Hammett plot of Lucchi s data yields a good straight line with the slope p = 1.06. These data suggest that the reaction proceeds by way of the chromic ester of hydrated benzaldehyde as intermediate, viz. 

The functionalized benzaldehyde derivative in Scheme 5-41 underwent diastere-oselective addition of diethyl phosphite catalyzed either by LLB (75 25 ratio of di-astereomers) or ALB (80 20 ratio) [30]. 

Chiral aluminum SALEN complexes have been used by Kee for asymmetric addition of dimethyl phosphite to benzaldehyde derivatives (Scheme 5-43). 

Samarium enolates 60 can be easily prepared by reduction of ct-bromocarboxylic acid esters with SmT. These enolates mediated well-defined synthesis of star-shaped block co-polymers 61 (Scheme 21 ).32 32l Sml3 also mediated the formation of samarium enolates. Phenacyl thiocyanate 6233 and cr-haloketone 6434 are converted to samarium(lll) enolate intermediates 63 and 65, respectively, which undergo addition to benzaldehyde derivatives affording the corresponding oy i-unsaturatcd ketones as shown in Schemes 22 and 23. 

Mukai et al.85 reported an asymmetric 1,3-dipolar cycloaddition of chromium(0)-complexed benzaldehyde derivatives. As shown in Scheme 5 52, heating chiral nitrone 171a, derived from Cr(CO)3-complexed benzaldehyde, with electron-rich olefins such as styrene (173a) or ethyl vinyl ether (173b) generates the corresponding chiral a.v-3,5-disubstitutcd isoxazolidine adduct 174 or... 

Column IV shows the product ratios in the presence of ultrasound and in the presence of pyridine. Overall there is the same trend with sonication, namely a slight shift from one-electron towards two-electron pathway, though here there is a higher yield of benzaldehyde derived by-products (approx. 16%). 

Atobe and Nonaka [67] have used a 20 kHz (titanium-alloy) sonic horn as the electrode (called sonoelectrode) for electroreductions of various benzaldehyde derivatives. This they did after insulating the submerged metal part of the horn-barrel with heat-shrink plastic. They found an improvement in current efficiency with insonation, but in addition noted some change in product selectivity towards one-electron-per-mole-cule products. Although the authors quote enhanced mass transfer across the electrode interface as the origin of the sonoelectrochemical trend towards products from the lesser amount of electrons per substrate molecule, the involvement of surface species on the reactive electrode provides a complication. 

The latter reaction could be repeated ten times without loss of activity of Yb-XN-1010. Similar results were obtained with ytterbium(III) loaded Amberlyst 15W resin in a two-step one-pot procedure first involving the formation of the active dimethyl acetal from a benzaldehyde derivative which was followed by in situ protection of sucrose (Scheme 4.17) [100]. 

Scheme 6.6 DCL-D Five benzaldehyde derivatives (23-27) and acetone cyano-hydrine (28), forming cyanohydrin adducts (29-33).

Scheme 6.9 DCL-E Five benzaldehyde derivatives (24,26,27,36, and 37) and 2-nitropropane (38), forming nitroaldol adducts (39-43).

Internal DCR of Nitroaldol Libraries (Scheme 6.10) [5,6] iDCR was demonstrated by using a conceptual nitroaldol library including five benzaldehyde derivatives (24,36, and 47-49) and one nitroalkane (50, DCL-F, Scheme 6.11). The benzaldehydes, all with a unique substitution pattern, were selected in order to make analysis clear and simple. However, one of the henzaldehydes contained a cyano functionality in the 2-position (49), deliberately making it a candidate for subsequent tandem cyclization following nitroalcohol formation. 5-exo-dig type cyclizations of hydrox-ynitriles to the corresponding iminolactones are expected [40,41], albeit unexplored [42 5], intramolecular transformations, which in this case could lead to possible kinetic resolution of the library. 

Scheme 6.11 DCL-F Five benzaldehyde derivatives (24, 36, and 47-49) and nitroethane (50), forming nitroaldol adducts (51-55).

Wang S et ai, Chaetopyranin, a benzaldehyde derivative, and other related metabohtes from Chaetomium globosum, an endophytic fungus derived from the marine red Agp Polysiphonia urceolata, J Nat Prod 69 622— 62 y, 2006. 

Attempts to deprotonate the benzaldehyde derivative 412 enantioselectively met with some success (see Scheme 169), but the reaction is complicated by benzylic lithiation Better results are obtained with the benzaldimine 441, which is Uthiated by 360 with good enantioselectivity and whose product is easily hydrolysed to the aldehyde 442 (Scheme 178). 

Several examples of Bi(0Tf)34H20-catalyzed Mannich-type reactions of various A-benzyloxycarbonylamino sulfones 1 with silyl enol ethers are summarized in Table 5. A-Benzyloxycarbonylamino sulfones 1 derived from differently substituted benzaldehydes were reacted with trimethyl(l-phenylvinyloxy)silane in dichloromethane at room temperature. The corresponding (3-amino ketones 24 were smoothly obtained (Table 5, entries 1-6). The reaction was efficient using electron-deficient benzaldehyde-derived sulfones, and the corresponding (3-amino ketones 24... 

This qualitative interpretation of structural and electronic similarity has also been employed to rationalize the fact that the quantum yield for the dioxetane derivative 6, in which the phenoxy substituent is directly linked to the peroxidic ring, is two orders of magnitude higher than for the dioxetane 7, in which the trigger function is separated by a methylene bridge. Furthermore, the different quantum yields were rationalized in terms of a competition between the intramolecular (pathway A) and intermolecular back-electron transfer (pathway B) in the decomposition of 7, whereas the intramolecular back-electron transfer was believed to occur exclusively in the decomposition of 6, due to the higher stability of the radical anion of the benzaldehyde derivative, as compared with the radical anion of acetone (Scheme 14). 

Two strategies for the synthesis of enantiomerically enriched diaryl methanols 27 are apparent first, asymmetric reductions of the corresponding diaryl ketones 36 [33], and, second, enantioselective aryl transfer reactions to the respective benzaldehyde derivatives 37 (Scheme 2.1.2.5) [34, 35]. 

Starting from the findings of the racemic cross-benzoin condensation [66], and assuming that aldehydes not accepted as donor substrates might still be suitable acceptor substrates, and vice versa, a mixed enzyme-substrate screening was performed in order to identify a biocatalytic system for the asymmetric cross-carboligation of aromatic aldehydes. For this purpose the reactions of 2-chloro-(40a), 2-methoxy- (40b) and 2-methylbenzaldehyde (40c), respectively, were studied with different enzymes in combination with benzaldehyde (Scheme 2.2.7.23) [67]. The three ortho-substituted benzaldehyde derivatives 40a-40c were... 

Moreover, no aldol or pinacol-type dimerization of the carbonyl compound was observed, even in the case of easily reducible benzophenone or benzaldehyde derivatives. As observed previously, the nature of the solvent is an important factor for the success of the reaction. Indeed, no homoallylic alcohols were formed in DMF. 

In the presence of copper(I) salts in acidic media o-ethynyl-benzaldehyde derivatives were found to cycloisomerise to 2-benzopyrylium salts (4.26.), The reaction, although working in the absence of catalyst too, was accelerated by the addition of different metal salts. The reaction was applied in the preparation of azaphilones and related molecules.30... 

Values of CArcH(OH)cr/CArCHO f°r eac benzaldehyde derivative were measured at 10-15 different sodium hydroxide concentrations in solutions containing fixed ethanol or DMSO concentrations ranging from 1 to 90 vol %. Since spectra obtained in the presence of 1% ethanol were indistinguishable from spectra recorded in purely aqueous solutions, it was possible to use absorbancies obtained in 1% ethanolic solutions for the calculation of pX2(H20) values. Ionization ratios were also determined in benzaldehyde solutions containing a constant concentration of sodium hydroxide (0.01M) and an ethanol or DMSO content which was varied between 1 and 98 vol %. 

Representative benzaldehyde derivatives [73k] and phenones [294] (Tables 4.30 and 4.31) display carbonyl shifts which are essentially influenced by steric repulsions and intramolecular hydrogen bonding. Steric repulsions by bulky alkyl groups in o, o position of the carbonyl group prevent coplanarity of carbonyl double bond and phenyl ring,... 

Table 4.30. 13C Chemical Shifts of Selected Benzaldehyde Derivatives in Deuteriochlo-roform as Solvent (Sc in ppm) [73 k].

The reaction was carried out in a batch reactor at 100 and 140°C. An equimolar solution of the two reactants (7 mmol), without solvent, was kept under stirring while heating up to reaction temperature. Then, 2 wt% of zeolite catalyst (0.0334 g) was added and the reaction started. The results obtained for the condensation of ethyl acetoacetate and the five benzaldehydes derivatives at 140°C on Na-Ge faujasite are given in scheme 2. High conversions with practically 100% selectivity are obtained with these catalysts. The order of activity of the zeolite samples is the same seen previously using benzaldehyde (Fig. 3). 

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