Benzaldehyde: benzoin from

Thiamin itself (in the absence of enzyme) had previously been shown to catalyse the formation of acetoin from acetaldehyde, albeit in very poor yield (Ukai et al., 1943 Mizuhara et al., 1951 Mizuhara and Handler, 1954). The reaction parallels the formation of benzoin from benzaldehyde, catalysed by cyanide ion. The mechanism of the latter reaction had been suggested in 1903 by Arthur Lapworth, who had shown how an aldehyde, R—CHO, could be converted into the equivalent of the anion R—C=0- (Lapworth, 1903). It is this idea that Breslow carried over to thiamin pyrophosphate and used to... 

It turned out that many of these aromatic substances have rather simple structures. Many contain a six-carbon unit that passes unscathed through various chemical reactions that alter only the rest of the structure. This group, CgHs—, is common to many substances, including benzaldehyde (isolated from the oil of bitter almonds), benzyl alcohol (isolated from gum benzoin, a balsam resin obtained from certain Southeast Asian trees), and toluene (a hydrocarbon isolated from tolu balsam). When any of these three compounds is oxidized, the QH5 group remains intact the product is benzoic acid (another constituent of gum benzoin). The calcium salt of this acid, when heated, yields the parent hydrocarbon QHg (eq. 4.1). 

Milller and co-workers recently developed an enantioselective benzoin dimerization using purified enzymes from Pseudomonas. The thiamine diphosphate (ThDP) dependent enzymes benzaldehyde lyase (BAL) and benzoylformate decarboxylase (BED) were found to catalyze the reversible benzoin condensation of aromatic aldehydes. The reaction is driven in the forward direction by the poor solubility of the benzoin products in aqueous media. A wide variety of aromatic aldehydes are accepted by BAL, and products of the (/ )-configuration are produced in excellent yield and enantiomeric purity. The (S)-enantiomer of benzoin is also available in high enantiomeric purity from a BAL-catalyzed kinetic resolution of rac-benzoin. In the presence of excess acetaldehyde, BAL selectively converts (i )-benzoin into (/ )-2-hydroxy-l-phenylpropanone, while the (iS)-benzoin enantiomer is not a substrate for the enzyme. At 49% conversion, (5)-benzoin is resolved to > 99% ee. BED can produce (i )-benzoin from benzaldehyde in comparable yield and enantiomeric purity with respect to BAL, but the substrate scope appears more limited. ... 

The mixture of benzaldehyde, potassium cyanide and alcohol is heated on the water-bath with an upright condenser for about half an hour. On cooling the liquid, the benzoin separates out as a mass of small colourless crystals, which are filtered and u ashed with a little alcohol. Yield, about 20 grams. A portion of the substance may be purified by recrystalhsation from spirit. 

R)-Benzoins and (/ )-2-hydroxypropiophcnonc derivatives are formed on a preparative scale by benzaldehyde lyase (BAL)-catalyzed C-C bond formation from aromatic aldehydes and acetaldehyde in aqueous buffer/DMSO solution with remarkable ease in high chemical yield and high optical purity (Eq. 8.112).303 Less-stable mixed benzoins were also generated via reductive coupling of benzoyl cyanide and carbonyl compounds by aqueous titanium(III) ions.304... 

The synthesis of 3-H-oxazol-2-ones was described by Nam et al. [69]. The substituted benzoin 89 was formed from the coupling of 3,4,5-trimethoxy-benzaldehyde 18 with 3-nitro-4-methoxybenzaldehyde, Scheme 22. Reaction with PMB-isocyanate and subsequent cyclization gave the protected oxazolone derivative 90. The PMB group was removed by reflux in TFA and reduction of the nitro-group was performed using Zn to give the combretoxazolone-aniline 91. 

Freshly distilled benzaldehyde (10 g.) is mixed with 25 c.c. of alcohol and a solution of 2 g. of potassium cyanide in 5 c.c. of water. The mixture is boiled on the water bath under reflux for one hour. Then the product is allowed to cool slowly, and the crystals which form, after being separated by filtration and washed with a little alcohol, are dried on the water bath. In order to obtain some quite pure benzoin a small sample of the crude product is recrystallised from a little alcohol. Melting point 134°. Yield about 90 per cent of the theoretical. 

Tetra-n-butylammonium cyanide is a better catalyst for benzoin condensation reactions than is sodium cyanide, and >70% yields are obtained under mild conditions [63, 64] tetra-ethylammonium cyanide is less effective. Polymer-supported ammonium catalysts have also been used to promote the benzoin reaction and, although yields are only moderate (40-60%), the convenience of removal of the catalyst is an advantage. Use of chiral ammonium groups produces an enantiomeric excess of chiral products from the condensation of benzaldehyde, but furfural tends to produce a racemate [65]. 

The benzoin reaction dates back to 1832 when Wohler and Liebig reported that cyanide catalyzes the formation of benzoin 6 from benzaldehyde 5, a seminal example in which the normal mode of polarity of a functional group was reversed (Eq. 1) [26], This reversal of polarity, subsequently termed Umpolung [27], effectively changes an electrophilic aldehyde into a nucleophilic acyl anion equivalent. 

Recently a complete product study has been carried out for benzil irradiated in cyclohexane.63 A complex mixture containing benzaldehyde, phenyl-cyclohexyl ketone, benzoin benzoate, benzoin, benzoic acid, and smaller amounts of other compounds containing from three to six benzyl groups was obtained. 

Further studies, with the substrate ratio altered from 1 3 to 1 100, were performed in order to suppress the formation of benzoin 12 and increase the yield of DMA-HPP 10. Although this strategy was successful, the results showed that even a 100-fold excess of dimethoxyacetaldehyde 8 (500 mM) relative to benzaldehyde 4 (5 mM) could not completely supress benzoin 12 formation catalyzed by variant 55E4. Furthermore, the formation of the mixed product DMA-HPP 10 was decreased by a factor of 2 relative to the 1 3 substrate mixture. Variant 55 E4 showed a 55-fold higher productivity with respect to the formation of DMA-HPP 10 under these conditions as compared to variant L476Q. The overall carboligation... 

From mechanistic considerations and assuming that cleavage and formation of (R)-benzoin are in equilibrium, BAL should also catalyze carboligation. Consequently, BAL-catalyzed acyloin condensation of benzaldehyde in an aqueous buffer/DMSO mixture resulted in almost quantitative formation of enantiomeri-cally pure (R)-benzoin [Scheme 2.2.7.21, Eq. (1)]. The reaction was carried out on a preparative scale with different aromatic and heteroaromatic aldehydes [62]. From the viewpoint of the organic-preparative chemist, it is important to mention that crude cell extracts of the recombinant E. coli strain overexpressing the BAL gene are sufficient for catalysis, hence, purification of the enzyme is not necessary. 

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... 

Using only benzaldehyde as substrate (see Fig. 3.1.8a), (R)-benzoin can be obtained on a 200 mg scale from a 40 mb two-phase system. This corresponds to a volumetric productivity of 53 g L d for the organic phase, or 20 g d with respect to the overall reaction volume. When using 2-chlorobenzaldehyde and 3-methoxybenzaldehyde as substrate in equimolar amounts, (R)-2-chloro-3 -methoxybenzoin is formed as the main product with approximately 80% selectivity (see Fig. 3.1.8b). The symmetric benzoins (2,2 -dichlorobenzoin, 3,3 -dimethoxybenzoin) are formed as side-products. The main product is obtained on a 150 mg scale, which corresponds to a volumetric productivity of 40 g L d with regard to the organic phase. 

In a 3-I. round-bottom flask fitted with a reflux condenser, 625 cc. of alcohol (95 per cent), 500 cc. of water, 500 g. of pure benzaldehyde and 50 g. of sodium cyanide (96-98 per cent) are placed. This mixture is then heated and kept boiling for 0.5 hour. In the course of about twenty minutes, crystals begin to separate from the hot solution. At the end of the thirty minutes, the solution is cooled, filtered with suction, and washed with a little water. The yield of dry crude benzoin, which is white or light yellow, amounts to 450 to 460 g. (90-92 per cent theory). In order to obtain it completely pure, the crude substance is recrystallized from alcohol, 90 g. of crude material being dissolved in about 700 cc. of boiling alcohol upon cooling, a yield of 83 g. of white, pure benzoin is obtained, m. p. 1290. 

The only good method for the preparation of benzoin1 appearing in the literature is by the action of potassium cyanide upon an alcoholic solution of benzaldehyde, a method described first by Wohler and later modified slightly by Zinin and Zincke. The other methods are of theoretical importance only and have, therefore, not been studied. Thus, by the reduction of benzil,2 and by the oxidation of hydrobenzoin,3 benzoin can be formed it happens, however, that both benzil and hydrobenzoin are commonly made from benzoin. 

Benzil. Benzil [134-81-6] (diphenylethanedione) is a yellow solid that crystallizes from alcohol in hexagonal prisms. Benzil can be prepared by the oxidation of benzoin [579-44-2] (2-hydroxy-2-phenylacetophenone) (298,299), which is itself prepared by the self-condensation of benzaldehyde (300). Benzil is commercially produced in Japan and is used as a uv resin curing sensitizer (301). It has also been suggested as a chigger repellant (302). 

Intramolecular protonation on the more hindered face of a steroid from a neighbouring hydroxyl group best explains a reversal of diastereoselectivity in the Birch reduction of styrene double bonds.266 The kinetics and product distribution of lithium metal reduction of benzaldehyde to benzyl alcohol in THF have been studied electron transfer from Li to PhCHO occurs in a slow step, but absorption of the PhCHO onto the metal surface is also crucial in determining the overall kinetics. The proposed mechanism successfully accounts for the formation of minor products, benzoin and... 

The photochemistry of benzaldehyde (90% 13C=0), 519, deoxybenzoin (99%) 13C=0), 521, and / -chloro benzoin (99% 13C=0), 522, in cyclohexane-Dn solution has been studied633 by spectroscopic techniques, such as XH chemically induced dynamic nuclear634 or electron polarization635 (CIDNP/CIDEP) or dynamic nuclear polarization636 (DNP). In all these cases the formation of benzaldehyde-D with emissive 13C=0 polarization has been observed and the results rationalized by intermolecular hydrogen (deuterium) abstraction by the photoexcited ketones from the solvent molecules and by reactions of cage-escaped radicals (equations 303-308), Benzoin, 520, is formed also. 

Potassium Cyanide is especially useful for condensing aromatic aldehydes (benzoin condensation). 38 Benzoin is formed from benzaldehyde ... 

A one-step construction of y,y-difunctionalized y-butyrolactones from benzoins or benzaldehydes via a tandem reaction promoted by l,3-dimethyl-imidazol-2-ylidene in the presence of methyl acrylate was reported by Zhai et al. [63]. So far, the exact mechanism of the reaction, as well as the role of the catalyst, has not been clarified. 

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