Commercial Manufacturing

Monkhouse (2006a) made the following illuminative comments in the context of the difficulties of preparing for commercial-scale manufacturing  

The difficulty of converting a laboratory concept into a consistent and well-characterized medical product that can be mass-produced has been highly under-rated. Problems in physical 

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The design of bioseparation unit operations is influenced by these governmental regulations. The constraints on process development grow as a recovery and purification scheme undergo licensing for commercial manufacture. 

Butanediol. 1,4-Butanediol [110-63-4] tetramethylene glycol, 1,4-butylene glycol, was first prepared in 1890 by acid hydrolysis of N,]S3-dinitro-l,4-butanediamine (117). Other early preparations were by reduction of succinaldehyde (118) or succinic esters (119) and by saponification of the diacetate prepared from 1,4-dihalobutanes (120). Catalytic hydrogenation of butynediol, now the principal commercial route, was first described in 1910 (121). Other processes used for commercial manufacture are described in the section on Manufacture. Physical properties of butanediol are Hsted in Table 2. 

Although acrylonitrile manufacture from propylene and ammonia was first patented in 1949 (30), it was not until 1959, when Sohio developed a catalyst capable of producing acrylonitrile with high selectivity, that commercial manufacture from propylene became economically viable (1). Production improvements over the past 30 years have stemmed largely from development of several generations of increasingly more efficient catalysts. These catalysts are multicomponent mixed metal oxides mostly based on bismuth—molybdenum oxide. Other types of catalysts that have been used commercially are based on iron—antimony oxide, uranium—antimony oxide, and tellurium-molybdenum oxide. 

In 1993 there were over 100 organisations undertaking plasma fractionation woddwide, having plant capacities ranging from 4 to 1800 m /yr. Virtually all of these plants use methods based on those originally devised. Table 2 Hsts the six commercial manufacturers in the United States and the largest plasma fractionators woddwide. 

A subsidiary of lEC and Toshiba Corp. called ONSI Corp. was formed for the commercial development, production, and marketing of packaged PAEC power plants of up to 1-MW capacities. ONSI is commercially manufacturing 200-kW PAEC systems for use in a PC25 power plant. The power plants are manufactured in a highly automated faciHty, using robotic techniques to assemble the repeating electrode, bipolar separator, etc, units into the fuel cell stack. 

Coal was the original feedstock for syngas at BeUe thus ethylene glycol was commercially manufactured from coal at one time. Ethylene glycol manufacture from syngas continues to be pursued by a number of researchers (10). 

A.luminum Hydride. Aluminum hydride is a relatively unstable polymeric covalent hydride that received considerable attention in the mid-1960s because of its potential as a high energy additive to soHd rocket propellants. The projected uses, including aluminum plating, never materialized, and in spite of intense research and development, commercial manufacture has not been undertaken. The synthetic methods developed were cosdy, eg. 

Preparation. Commercial manufacture of LiAlH uses the original synthetic method (44), ie, addition of a diethyl ether solution of aluminum chloride to a slurry of lithium hydride (Fig. 2). 

The polymerization of monomers to form hydrocarbon resins is typically carried out by either the direct addition of catalyst to a hydrocarbon fraction or by the addition of feed to a solvent—catalyst slurry or solution. Most commercial manufacturers use a continuous polymerization process as opposed to a batch process. Reactor temperatures are typically in the range of 0—120°C. 

Maleic anhydride and the two diacid isomers were first prepared in the 1830s (1) but commercial manufacture did not begin until a century later. In 1933 the National Aniline and Chemical Co., Inc., installed a process for maleic anhydride based on benzene oxidation using a vanadium oxide catalyst (2). Maleic acid was available commercially ia 1928 and fumaric acid production began in 1932 by acid-catalyzed isomerization of maleic acid. 

Another example is the du Pont process for the production of adiponitrile. Tetrakisarylphosphitenickel(0) compounds are used to affect the hydrocyanation of butadiene. A multistage reaction results in the synthesis of dinitrile, which is ultimately used in the commercial manufacture of nylon-6,6 (144-149). 

PMP can also crystallise in several crystalline forms (28). Form I is produced during crystallisation from the melt. This is the only crystalline form present in commercially manufactured articles. Other crystalline modifications ate formed when the polymer is crystallised from solution (28). 

Calcium Pyrophosphates. As is typical of the pyrophosphate salts of multiple-charged or heavy-metal ions, the calcium pyrophosphates are extremely insoluble ia water. Calcium pyrophosphate exists ia three polymorphic modifications, each of which is metastable at room temperature. These are formed progressively upon thermal dehydration of calcium hydrogen phosphate dihydrate as shown below. Conversion temperatures indicated are those obtained from thermal analyses (22,23). The presence of impurities and actual processing conditions can change these values considerably, as is tme of commercial manufacture. 

Manufacture and Synthesis. The commercial manufacturing process is based on Scheele s original procedure starting with cmde gaHic acid. 

Phenylenediamines can be dia2oti2ed and tetra2oti2ed (20), giving intermediates for various a2o dyes (qv). Their dia2onium salts are commercially manufactured and used in photography. 

Propanol has been manufactured by hydroformylation of ethylene (qv) (see Oxo process) followed by hydrogenation of propionaldehyde or propanal and as a by-product of vapor-phase oxidation of propane (see Hydrocarbon oxidation). Celanese operated the only commercial vapor-phase oxidation faciUty at Bishop, Texas. Since this faciUty was shut down ia 1973 (5,6), hydroformylation or 0x0 technology has been the principal process for commercial manufacture of 1-propanol ia the United States and Europe. Sasol ia South Africa makes 1-propanol by Fischer-Tropsch chemistry (7). Some attempts have been made to hydrate propylene ia an anti-Markovnikoff fashion to produce 1-propanol (8—10). However, these attempts have not been commercially successful. 

Commercial Manufacture of Pyridine. There are two vapor-phase processes used in the industry for the synthesis of pyridines. The first process (eq. 21) uti1i2es formaldehyde and acetaldehyde as a co-feed with ammonia, and the principal products are pyridine (1) and 3-picoline (3). The second process produces only alkylated pyridines as products. 

Commercial Manufacture of Specific Pyridine Bases. Condensation of paraldehyde with ammonia at 230°C and autogenous pressure (eq. 22) is used to manufacture 5-ethyl-2-methylpyridine (7). This is one of the few Hquid-phase processes used in the industry to make relatively simple aLkylpyridines, and one of the few processes known to make a single alkylpyridine product selectively. 

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

Pyrrohdinone (2-pyrrohdone, butyrolactam or 2-Pyrol) (27) was first reported in 1889 as a product of the dehydration of 4-aminobutanoic acid (49). The synthesis used for commercial manufacture, ie, condensation of butyrolactone with ammonia at high temperatures, was first described in 1936 (50). Other synthetic routes include carbon monoxide insertion into allylamine (51,52), hydrolytic hydrogenation of succinonitnle (53,54), and hydrogenation of ammoniacal solutions of maleic or succinic acids (55—57). Properties of 2-pyrrohdinone are Hsted in Table 2. 2-Pyrrohdinone is completely miscible with water, lower alcohols, lower ketones, ether, ethyl acetate, chloroform, and benzene. It is soluble to ca 1 wt % in aUphatic hydrocarbons. 

Synthesis and Manufacture of Amines. The chemical and busiaess segments of amines (qv) and quaternaries are so closely linked that it is difficult to consider these separately. The majority of commercially produced amines origiaate from three amine raw materials natural fats and oils, a-olefins, and fatty alcohols. Most large commercial manufacturers of quaternary ammonium compounds are fully back-iategrated to at least one of these three sources of amines. The amines are then used to produce a wide array of commercially available quaternary ammonium compounds. Some iadividual quaternary ammonium compounds can be produced by more than one synthetic route. 

Pha.se-Tra.nsfer Ca.ta.lysts, Many quaternaries have been used as phase-transfer catalysts. A phase-transfer catalyst (PTC) increases the rate of reaction between reactants in different solvent phases. Usually, water is one phase and a water-iminiscible organic solvent is the other. An extensive amount has been pubHshed on the subject of phase-transfer catalysts (233). Both the industrial appHcations in commercial manufacturing processes (243) and their synthesis (244) have been reviewed. Common quaternaries employed as phase-transfer agents include benzyltriethylammonium chloride [56-37-17, tetrabutylammonium bromide [1643-19-2] tributylmethylammonium chloride [56375-79-2] and hexadecylpyridinium chloride [123-03-5]. 

Carbon and Graphite. Carbon (qv) and graphite [7782 2-5] have been used alone to make refractory products for the lower blast furnace linings, and electrodes for steel and aluminum production. They are also commonly used in conjunction with other refractory raw materials. These materials are highly refractory nonwettable materials and are useful refractories in nonoxidizing environments. Carbon blacks are commercially manufactured, whereas graphite for refractory use has to be mined. 

At equihbrium the vapors are predominantly hydrogen and sihcon tetrachlorides. However, these can be easily removed from the trichlorosilane and recycled. A once-common commercial manufacturing procedure for sihcon tetrachloride was the reaction of chlorine gas with sihcon carbide. 

A wide variety of organosiUcone resins containing a combination of M, D, T, and/or Q groups have been prepared and many are commercially manufactured. In addition, resins containing hydrosilation-reactive SiH and SiVi groups or other functionahties, including OH and phenyl groups, are known. Two classes of sihcone resins are most widely used in the sihcone industry MQ and TD resins. 

MQ resins are commercially manufactured by one of two processes the ethyl sihcate or the sodium sihcate process. In the ethyl sihcate process, these resins were first prepared by cohydrolysis of tetraethoxysilane and trimethylchlorosilane in the presence of an aromatic solvent (eq. 34). This process is versatile and reproducible it can be used to prepare soluble MQ resins with M/Q ratios ranging between 0.6 and 4. The products of these reactions typically contain high levels of residual alkoxysilane groups. 

Commercially, soap is most commonly produced through either the direct saponification of fats and oils with caustic or the hydrolysis of fats and oils to fatty acids followed by stoichiometric (equal molar) neutralization with caustic. Both of these approaches yield workable soap in the form of concentrated soap solutions (- 70% soap). This concentration of soap is the target on account of the aqueous-phase properties of soap as well as practical limitations resulting from these properties. Hence, before discussing the commercial manufacturing of soap, it is imperative to understand the phase properties of soap. 

Styrene. Commercial manufacture of this commodity monomer depends on ethylbenzene, which is converted by several means to a low purity styrene, subsequendy distilled to the pure form. A small percentage of styrene is made from the oxidative process, whereby ethylbenzene is oxidized to a hydroperoxide or alcohol and then dehydrated to styrene. A popular commercial route has been the alkylation of benzene to ethylbenzene, with ethylene, after which the cmde ethylbenzene is distilled to give high purity ethylbenzene. The ethylbenzene is direcdy dehydrogenated to styrene monomer in the vapor phase with steam and appropriate catalysts. Most styrene is manufactured by variations of this process. A variety of catalyst systems are used, based on ferric oxide with other components, including potassium salts, which improve the catalytic activity (10). 

The commercial manufacture of carbon tetrachloride by chlorination of carbon disulfide yields sulfur monochloride. 

Poly(viayl alcohol) (PVA), a polyhydroxy polymer, is the largest-volume synthetic, water-soluble resin produced in the world. It is commercially manufactured by the hydrolysis of poly(vinyl acetate), because monomeric vinyl alcohol caimot be obtained in quantities and purity that makes polymerisation to poly(vinyl alcohol) feasible (1 3). 

Most barium compounds are prepared from reactions of barium carbonate [513-77-9] BaCO, which is commercially manufactured by the "black ash" process from barite and coke ki a process identical to that for strontium carbonate production. Depending on the co-product, soda ash and/or carbon dioxide are also consumed. 

Commercial manufacture of methyl bromide is generally based on the reaction of hydrogen bromide with methanol. For laboratory preparation, the addition of sulfuric acid to sodium bromide and methanol has been used (80). Another method involves the treatment of bromine with a reducing agent, such as phosphoms or sulfur dioxide, to generate hydrogen bromide (81). 

One of the butadiene dimeri2ation products, COD, is commercially manufactured and used as an intermediate in a process called FEAST to produce linear a,C0-dienes (153). COD or cyclooctene [931-87-3], obtained from partial hydrogenation, is metathesi2ed with ethylene to produce 1,5-hexadiene [592-42-7] or 1,9-decadiene [1647-16-1], respectively. Many variations to make other diolefins have been demonstrated. Huls AG also metathesi2ed cyclooctene with itself to produce an elastomer useful in mbber blending (154). The cycHc cis,trans,trans-tn.en.e described above can be hydrogenated and oxidi2ed to manufacture dodecanedioic acid [693-23-2]. The product was used in the past for the production of the specialty nylon-6,12, Qiana (155,156). 

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