Production on a technical scale

Further modifications were then made in this hydrogen phosphite method of preparing di-isopropyl phosphorofluoridate in order to put it on an industrial scale. 

After a large number of experiments, we found that the preparation could be run virtually as a one-stage process. The whole process consists simply in adding phosphorus trichloride to isopropyl alcohol, dissolved in a solvent such as carbon tetrachloride, without external cooling. The crude product (still in the solvent) is chlorinated and then heated with an inorganic fluoride, e.g. sodium fluoride. After filtration, the solvent is distilled off and the pure di-isopropyl phosphorofluoridate distilled.  

This process is very easily carried out by efficient workers and yields are of the order of 70 per cent. It has formed the basis of the method in general use for the production not only of this substance but also of related compounds. An American patent gives closely similar details. 

A distinctly different method of synthesizing the esters of phosphorofluoridic acid consisted in the partial fluorination of phosphorus oxychloride with antimony trifluoride (using a specially designed apparatus and phosphorus pentachloride as catalyst) to give phosphorus oxydichlorofluoride, POClaF. In the latter compound the chlorine atoms proved to be much more reactive than the fluorine atom, and with an alcohol the dialkyl phosphorofluoridate was readily obtained in high yield.  

Although the action of POClaF on an alcohol cannot compete with the hydrogen phosphite method for large-scale work, the (vmer was found extremely valuable for exploratory purposes. In particular, it was found possible to prepare diaryl phosphoro-fluoridates (e.g. (C,H50)aPOF) and diethyl phosphorofluorido-dithiolate (diethyl dithiofluorophosphonate, (CaH5S)aPOF) by the action of phosphorus oxydichlorofluoride on the appropriate phenol or mercaptan. 

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Only a few natural sources of fatty alcohols were known at this time. Production on a technical scale could be first realized by the reduction of methyl or butyl esters of fatty acids with metallic sodium after the Bouveault-Blanc process. Nearly simultaneously, the high-pressure hydrogenation of fatty acids to the resulting alcohols was developed by Schrauth. Hence, fatty alcohols were soon available on the market in a price range that made it possible to produce fatty alcohol sulfates for use in detergents. 

The formed aldehydes are not usually the final products on a technical scale. Thus, mono-, di-, and triformylated methyl stearates derived from the hydroformylation... 

First production of liquid oxygen on a technical scale (C. von Linde). 

For the production of ester sulfonates on a technical scale, Stein et al. studied the bleaching and neutralization conditions in great detail [12,33,52,53]. They had the best results when they bleached the sulfonated product with hydrogen... 

For Cl2 or 02 evolution the stability of ruthenium based electrodes is not sufficient on a technical scale. Therefore the possibility of stabilizing the ruthenium oxide without losing too much of its outstanding catalytic performance was investigated by many groups. For the Cl2 process, mixed oxides with valve metals like Ti or Ta were found to exhibit enhanced stability (see Section 3.1), while in the case of the 02 evolution process in solid polymer electrolyte cells for H2 production a mixed Ru/Ir oxide proved to be the best candidate [68, 80]. 

Oxidation of methylpyridines in 60-80 % sulphuric acid at a lead dioxide anode leads to the pyridinecarboxylic acid [213]. The sulphuric acid concentration is critical and little of the product is formed in dilute sulphuric acid [214]. In these reactions, electron loss from the n-system is driven by concerted cleavage of a carbon-hydrogen bond in the methyl substituent. This leaves a pyridylmethyl radical, which is then further oxidised to the acid, fhe procedure is run on a technical scale in a divided cell to give the pyridinecarboxylic acid in 80 % yields [215]. Oxida-tionof quinoline under the same conditions leads to pyridine-2,3-dicarboxylic acid [214, 216]. 3-HaIoquino ines afford the 5-halopyridine-2,3-dicarboxylic acid [217]. Quinoxaline is converted to pyrazine-2,3-dicarboxylic acid by oxidation at a copper anode in aqueous sodium hydroxide containing potassium permanganate [218]. 

The oxidation of propargyl alcohol to the acid and of but-2-yne-l,4-diol to acetylene dicarboxylic acid is carried out on a technical scale at a lead dioxide anode in sulphuric acid [4, 5]. Electrochemical oxidation of acetylenic secondary alcohols to the ketone at lead dioxide in aqueous sulphuric acid [4], gives better results than the cliromic acid based process of Jones [6], Oxidation of aminoalkan-1-ols to the amino acid at a lead dioxide anode in sulphuric acid is achieved in 31 -73 % 5delds [7]. This route is applied to the technical scale production of (l-alanine from 3-aminopropanol in an undivided cell [8]. 

Very recently, Hu et al. claimed to have discovered a convenient procedure for the aerobic oxidation of primary and secondary alcohols utilizing a TEMPO based catalyst system free of any transition metal co-catalyst (21). These authors employed a mixture of TEMPO (1 mol%), sodium nitrite (4-8 mol%) and bromine (4 mol%) as an active catalyst system. The oxidation took place at temperatures between 80-100 °C and at air pressure of 4 bars. However, this process was only successful with activated alcohols. With benzyl alcohol, quantitative conversion to benzaldehyde was achieved after a 1-2 hour reaction. With non-activated aliphatic alcohols (such as 1-octanol) or cyclic alcohols (cyclohexanol), the air pressure needed to be raised to 9 bar and a 4-5 hour of reaction was necessary to reach complete conversion. Unfortunately, this new oxidation procedure also depends on the use of dichloromethane as a solvent. In addition, the elemental bromine used as a cocatalyst is rather difficult to handle on a technical scale because of its high vapor pressure, toxicity and severe corrosion problems. Other disadvantages of this system are the rather low substrate concentration in the solvent and the observed formation of bromination by-products. 

This commonest derivative of sulphur trioxide and the most important of all acids from a technical and commercial aspect, has been known from early times, although its production on a large scale and at a low price dates from the success of the lead chamber process of manufacture, which revolutionised chemical industry in the early part of the nineteenth century. 

The synthesis of fluotrimazole starts from m-xylene. Peroxide catalyzed perchlorination converts this to m-trichloromethyl-benzo-trichloride. m-Trichloromethyl-benzotrifluoride is then obtained by selective chlorine/fluorine exchange. This key product is also readily accessible on a technical scale by conproportionation of the two corresponding m-trihalomethyl-benzotrihalogenides. Friedel-Crafts reaction with benzene leads to trifluoromethyl-tritylchloride, which reacts smoothly with 1,2,4-triazole in polar solvents to give fluotrimazole. 

The oxidation of butane (or butylene or mixtures thereof) to maleic anhydride is a successful example of the replacement of a feedstock (in this case benzene) by a more economical one (Table 1, entry 5). Process conditions are similar to the conventional process starting from aromatics or butylene. Catalysts are based on vanadium and phosphorus oxides [11]. The reaction can be performed in multitubular fixed bed or in fluidized bed reactors. To achieve high selectivity the conversion is limited to <20 % in the fixed bed reactor and the concentration of C4 is limited to values below the explosion limit of approx. 2 mol% in the feed of fixed bed reactors. The fluidized-bed reactor can be operated above the explosion limits but the selectivity is lower than for a fixed bed process. The synthesis of maleic anhydride is also an example of the intensive process development that has occurred in recent decades. In the 1990s DuPont developed and introduced a so called cataloreactant concept on a technical scale. In this process hydrocarbons are oxidized by a catalyst in a high oxidation state and the catalyst is reduced in this first reaction step. In a second reaction step the catalyst is reoxidized separately. DuPont s circulating reactor-regenerator principle thus limits total oxidation of feed and products by the absence of gas phase oxygen in the reaction step of hydrocarbon oxidation [12]. 

The procedures for the production of supported catalysts can be divided into two main groups, namely selective removal of one or more components out of usually nonporous bodies of a compound containing precursors of the support and the active componcnt(s), and application of (a precursor of) the active components) onto a separately produced support [2] Both procedures are carried out extensively on a technical scale... 

More examples for applied organocatalysis are presented by H. Groger, who gives an overview of organocatalytic methods already applied on a technical scale. Based on case studies, he shows several examples that satisfy the criteria of a technically feasible process such as high catalyst activity and stability, economic access, sustainability, atom economy, and high volumetric productivity. 

Because of the high temperatures needed and the problems encountered in confining a plasma of ions and electrons at these temperatures, many efforts in research and development are necessary until production of energy by controlled thermonuclear reactions on a technical scale becomes possible. 

Nitrobenzene can be produced on a technical scale in yields up to 98 percent by nitration of benzene with mixed acid. The sulfuric acid serves as a solvent and generates the nitronium ion, which is the attacking electrophile [5]. Nitrobenzene itself may be further nitrated with a mixed acid giving m-dinitrobenzene. The o- and p-dini-trobenzenes are removed as water-soluble products by treating the nitration product with aqueous sodium sulfite, sodium 0- and p-nitrobenzenesulfonates being formed. The residual m-nitrobenzene is separated from the aqueous layer, washed with water and finally dried [11]. 

N-Methyl-N-methoxycarbamoyl chloride made by phos-genation of methoxy methyl amine hydrochloride is a very useful intermediate for the synthesis of N-methoxy ureas herbicides. However, we found the method to be unsatisfactory for the production on a large scale, because of rather low yields and also of technical difficulties. To overcome these problems, we developed a new procedure based on the reaction of phosgene with methoxy methyl amine sulfate as depicted in scheme 124. Sulfuric acid formed is easily removed by decantation (Ref. 177). 

The catalyst may be also preformed separately on a large scale and is stable over a long period. Analysis of the product mixture indicates only small amounts of byproducts such as butadiene dimers. On a technical scale, unreacted butadiene is easy recovered and the process can be optimized with respect to TON and selectivity. Further studies of several reaction... 

The application of homogeneous enantioselective catalysts on a technical scale presents some very special challenges and problems [3, 4, 6, 7], Some of these problems are due to the special manufacturing situation of the products involved, others to the nature of the enantioselective catalytic processes. 

This section deals primarily with the carburization of tungsten powder, the most widely used process for producing WC on a, technical scale. Also, the carburization performed in melts is discussed briefly owing to historical reasons and the production of hard facing alloys. Finally, the formation of coarse tungsten carbide crystals in auxiliary melts ( Menstruum WC) is discussed. 

On a technical scale, batch and continuous operation are used. Batch crystallization leads to better consistency of the product, but the continuous process is more economic. 

The most important question is of course Are these studies relevant, or in other words, are these processes actually typical and are they applied for commercial production Also here, the answer is an almost unqualified YES. As discussed below, we are sure to have a representative mix of different types of catalysts, transformations and intended use of the chiral products. There are two caveats. Firstly, for various reasons, a number of important technically mature enantiose-lective processes are not described in our book. In order to at least partially remedy this gap we have listed selected missing processes and some relevant references for further reading. Secondly, even though more than half of the processes are either already applied on a technical scale or their introduction is scheduled, not all processes are or will in fact be used commercially (sometimes this was actually the reason, why clearance was given to publish the results ). In any case, we have made sure that only processes are included in our collection where the technical feasibility has been demonstrated at least in a pilot setting. 

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