Benzaldehyde production processes

Vapor-phase oxidation of toluene to produce benzoic acid and benzaldehyde has been tried utilizing several different catalysts, but yields are low and the process cannot compete with the Hquid-phase process (see Benzaldehyde). Other processes for the production of benzoic acid are presendy of htde commercial importance. 

SNIF-NMR is a powerful method for the authentication analysis of benzaldehyde products. However, manufacturing processes may cause the deuterium to shift on the carbonyl site. In some cases, the current SNIF NMR method cannot differentiate abnormal distribution of deuterium caused by adulteration or by production processes that lead to false negative or false positive conclusions of a product. Deuterium on the aromatic sites of benzaldehyde is more stable and is not affected by the known manufacturing processes. The aromatic deuterium distribution is very specific and can be used to classify benzaldehyde products from fossil or different botanical origins. The proposed improvement needs to be further developed and validated. 

At the end of 2004, phenol production at DSM stopped. The operating process of the existing toluene oxidation plant changed dramatically, producing much less benzoic acid but maintaining the same level of benzaldehyde production. 

BENZALDEHYDE The precursor for speed. It makes up nearly 100% of bitter almond oil. Not a very popular oil with the DEA. Some hints Benzaldehyde is indispensable for the flavoring industry. It is the flavor in almond extract and synthetic benzaldehyde is used in all cherry flavorings. Also, there is currently a little loophole in the system when it comes to a product called Roasted Cassia Oil . Apparently, some manufacturers take cassia oil and run it through some sort of industrial process to change it into benzaldehyde. No one wanted to tell Strike the particulars of how this was done. But one company chemist gave me some hints (You can get really chatty with some of these guys). 

METHOD 1 This section is going to be as thoroughly helpful to those interested in X production as it will be to those interested in amphetamine production. The process is known as the Knoeve-nagel-Walter condensation which can turn a substituted benzal-dehyde such as piperonal (X) or plain old benzaldehyde (speed) into an intermediate called a p-nitropropene. This intermediate can then be transformed into MDA (Benzedrine for speed) or MD-P2P (P2P for speed) depending on the capabilities of the chemist. 

Today, the air oxidation of toluene is the source of most of the world s synthetic benzaldehyde. Both vapor- and Hquid-phase air oxidation processes have been used. In the vapor-phase process, a mixture of air and toluene vapor is passed over a catalyst consisting of the oxides of uranium, molybdenum, or related metals. High temperatures and short contact times are essential to maximize yields. Small amounts of copper oxide maybe added to the catalyst mixture to reduce formation of by-product maleic anhydride. 

Benzaldehyde is produced ia the United States by Kalama Chemical Incorporated, Kalama, Washington and ia Canada by Chatterton Petrochemical Corporation, Delta, British Columbia. Both plants were constmcted by The Dow Chemical Company ia the early 1960s to produce phenol from benzoic acid and both produce benzaldehyde as a by-product of that process (6). Production and sales figures for benzaldehyde are not available. 

A series of chiral boron catalysts prepared from, e.g., N-sulfonyl a-amino acids has also been developed and used in a variety of cycloaddition reactions [18]. Corey et al. have applied the chiral (S)-tryptophan-derived oxazaborolidine-boron catalyst 11 and used it for the conversion of, e.g., benzaldehyde la to the cycloaddition product 3a by reaction with Danishefsky s diene 2a [18h]. This reaction la affords mainly the Mukaiyama aldol product 10, which, after isolation, was converted to 3a by treatment with TFA (Scheme 4.11). It was observed that no cycloaddition product was produced in the initial step, providing evidence for the two-step process. 

An alternative process for the synthesis of vinylepoxides was clearly needed, so reactions with stoichiometric amounts of chiral sulfide were investigated (Scheme 9.16a) [74]. Indeed, when benzyl sulfonium salt 20 was treated with unsaturated aldehydes, the ees and des were high in all cases, whereas the yields [75] were highly substrate-dependent. The same products could be formed by treatment of an unsaturated sulfonium salt with benzaldehyde, but the yields and se-lectivities were generally slightly lower. 

Ephedrine and pseudoephediine are a vasodilator and decongestant respectively used widely in the treatment of asthma and the symptoms of colds and influenza. These pharmaceuticals were derived originally fi om the plant Ephedra sinica and used in traditional Chinese medicinal preparations. Although some are still produced fi om such sources, the major production is via a fermentation process followed by a chemical catalytic reaction. As shown in Figure 1, the intermediate / -phenylacetylcarbinol (PAC) is produced by decarboxylation of pyruvate followed by ligation to benzaldehyde. 

In current industrial practice, benzaldehyde is added to fermenting baker s yeast Saccharomyces cerevisiae) with resultant PAC production occurring from the yeast-derived pyruvate. Typically PAC concentrations of 12-15 g F are produced at yields of 65-70% theoretical in a 10-12 h biotransformation process. [2], Appreciable concentrations of benzyl alcohol are produced as by-product due to oxidoreductase activity in the fermentative yeast. 

An enzymatic process using partially purified pyruvate decarboxylase (PDC) with added pyruvate overcomes the problems of benzyl alcohol formation and limiting availability of pyruvate [3]. As a result increased concentrations, yields and productivities of PAC were achieved with concentrations of PAC in excess of 50 g f (330 mM) in 28 h and yields on benzaldehyde above 95% theoretical [4-6]. Screening of a wide range of bacteria, yeasts and other fungi as potential sources of stable, high activity PDC for production of PAC confirmed a strain of the yeast Candida utilis as the most suitable source of PDC [7]. 

The most limiting factor for enzymatic PAC production is the inactivation of PDC by the toxic substrate benzaldehyde. The rate of PDC deactivation follows a first order dependency on benzaldehyde concentration and reaction time [8]. Various strategies have been developed to minimize PDC exposure to benzaldehyde including fed-batch operation, immobilization of PDC for continuous operation and more recently an enzymatic aqueous/octanol two-phase process [5,9,10] in which benzaldehyde is continuously fed from the octanol to the enzyme in the aqueous phase. The present study aims at optimal feeding of benzaldehyde in an aqueous batch system. 

Prediction of benzaldehyde pulse feeding profile to optimize the production of PAC in fed batch PAC biotransformation process at 6°C. A molar ratio of 1.2 1 pyruvate to benzaldehyde was used, with AR grade benzaldehyde and a 1.4 M solution of pyruvate used in the simulated feeding. 

It is relevant also to compare the results in Fig.5 with previously published data for PAC production under similar environmental conditions, where with higher concentrations of initial benzaldehyde (600 mM), pyruvate (400 mM) and PDC activity (8.4 U ml ) a similar maximum concentration of PAC of 330 mM was produced [6]. PDC stability was similar in both processes with half life values of approximately 27h. However, PAC production was much faster in the benzaldehyde emulsion system, presumably due to higher initial enzyme concentration. 

Bruggink (1996) has given an account of how the production of cefalexin, which is the largest cephalosporin in the market, can be converted from a ten-step process based on benzaldehyde and penicillin into a six-step process where biocatalysis is involved in three steps. The wastewater stream, containing 30-40 kg of unwanted materials in the conventional process, has been substantially reduced. Similarly, Van Loon et al. (1996) have given details of fermentation processes for cleaner and cheaper compared to the process practised so far. 

A more general reaction between kojic acid and aldehydes is a trimolecu-lar condensation discovered by Barham and Reed." By a process of elimination, they arrived at the conclusion that C6 of kojic acid was most probably the point of attack two molecules of kojic acid reacted with one molecule of the aldehyde, with the elimination of one molecule of water, giving a product of structure LXXV. Such compounds were prepared from kojic acid and the following aldehydes the normal alkanals from formaldehyde to heptanal, benzaldehyde, cinnamaldehyde, hydrocinnamaldehyde, 2-furaldehyde, and acrolein. The compound derived from kojic acid and benzaldehyde (LXXV, R = phenyl) was also obtained by treating LXXII (R = phenyl) with hot, aqueous sodium carbonate.92... 

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