Continuous processing

Unlike most of the rest of the chemical industry, continuous processing is a relatively new concept in API manufacture. It is therefore necessary to understand where the industry has come from in terms of manufacturing methods before considering the factors necessary for change. 

Until recently there has been a great resistance to change from this batch processing model, driven by several factors  

Batch processing is familiar to both the industry and its regulators and therefore any change was seen as carrying a high regulatory risk. 

As a result, the manufacturing equipment and methods used by the industry would have been familiar to the founding fathers of the industry - it has been said that we are still using the same pots and pans that were used in the nineteenth century. 

Studies of the phase behaviour at ambient temperature within the separator [43] show that there is significant solubility of the product nonanal within the fluorous phase and vice versa. Although this does not present a problem for the nonanal (it will simply be recycled to the reactor and create a steady state, it does mean that fluorous solvent is always being lost. The loss of the fluorous solvent (2.8 mol% into pure nonanal), as for the catalyst and the free ligand [41] is much more significant at low conversion, so 

The drop in conversion at the start of the reaction is much greater than expected just on the basis of transferring from a batch to a continuous reaction. It occurs because there is also substantial leaching of rhodium (300 ppm) at the start of the reaction, either because the catalyst has not preformed properly or because there is oxygen in the system and some of the phosphine is oxidised. Rhodium leaching increases at the end of the reaction (115 ppm), presumably because phosphine is lost to the organic phase and there is insufficient to keep the catalyst as [RhH(CO) P(l-C6H4C6Fi3)3 3], but is about 20-30 ppm for most of the reaction. 

The main conclusions to be drawn from this study are that the reactor design works well, and that steady state continuous flow operation requires excellent mixing of the gases and two liquid phases and high conversions. Improvements in the catalyst (ligand) are required to reduce leaching still further, but commercialisation will also require a different reactor design or more than one CSTR in series. 

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The recycling of material is an essential feature of most chemical processes. Therefore, it is necessary to consider the main factors which dictate the recycle structure of a process. We shall start by considering the function of process recycles and restrict consideration to continuous processes. Later the scope will be extended to include batch processes. 

Achieving complete conversion of FEED to PRODUCT in the reactor usually requires an extremely long residence time, which is normally uneconomic (at least in continuous processes). Thus, if there is no byproduct formation, the initial reactor conversion is set to be around 95 percent, as discussed in Chap. 2. The reactor effluent thus contains unreacted FEED and PRODUCT (Fig. 4.1a). 

In a batch process, the main steps operate discontinuously. In contrast with a continuous process, a batch process does not deliver its product continuously but in discrete amounts. This means that... 

Given the choice of a batch rather than continuous process, does this need a different approach to the synthesis of the reaction and separation and recycle system In fact, a different approach is not needed. We start by assuming the process to be continuous and then, if choosing to use batch operation, replace continuous steps by batch steps. It is simpler to start with continuous process operation... 

Example 4.5 Given that a low rate of production is required, convert the continuous process from Example 4.4 into a batch process. Preliminary sizing of the equipment indicates that the duration of the processing steps are given in Table 4.7. ... 

Batch processes can be synthesized by first synthesizing a continuous process and then converting it to batch operation. The process yield is an important measure of both raw materials efficiency and environmental impact. 

In addition to these variables which result from the batch nature of the process, there are still the variables considered earlier for continuous processes ... 

Process operations. The third source of process waste we can classify under the general category of process operations. Operations such as start-up and shutdown of continuous processes, product changeover, equipment cleaning for maintenance, tank filling, etc. all produce waste. 

Sources of waste in process operations a. Start-up I shutdown in continuous processes... 

In continuous processes, all those sources of process waste associated with start-up and shutdown also apply to product changeover in multiproduct plants. 

In both batch and continuous processes, it may be necessary to clean equipment to prevent contamination of new product. Materials used for equipment cleaning often cannot be recycled, leading to waste. 

Design continuous processes for flexible operation, e.g., high turndown rate rather than shutdown. 

Delayed Coking", is a semi-continuous process, developed at the end of the 1930 s. The reaction is conducted at 450-500°C under relatively low pressure, four atmospheres, maximum. 

Industrial production is often based on transformation of this laboratory method into a continuous process (10). Another route is acetonitrile [75-05-8] hydration ... 

Continuous processes have been developed for the alcohols, operating under pressure with Hquid ammonia as solvent. Potassium hydroxide (206) or anion exchange resins (207) are suitable catalysts. However, the relatively small manufacturing volumes militate against continuous production. For a while a continuous catalytic plant operated in Raveima, Italy, designed to produce about 40,000 t/yr of methylbutynol for conversion to isoprene (208,209). 

Manufacturing processes have been improved by use of on-line computer control and statistical process control leading to more uniform final products. Production methods now include inverse (water-in-oil) suspension polymerization, inverse emulsion polymerization, and continuous aqueous solution polymerization on moving belts. Conventional azo, peroxy, redox, and gamma-ray initiators are used in batch and continuous processes. Recent patents describe processes for preparing transparent and stable microlatexes by inverse microemulsion polymerization. New methods have also been described for reducing residual acrylamide monomer in finished products. 

Single-reaction-step processes have been studied. However, higher selectivity is possible by optimizing catalyst composition and reaction conditions for each of these two steps (40,41). This more efficient utilization of raw material has led to two separate oxidation stages in all commercial faciUties. A two-step continuous process without isolation of the intermediate acrolein was first described by the Toyo Soda Company (42). A mixture of propylene, air, and steam is converted to acrolein in the first reactor. The effluent from the first reactor is then passed directiy to the second reactor where the acrolein is oxidized to acryUc acid. The products are absorbed in water to give about 30—60% aqueous acryUc acid in about 80—85% yield based on propylene. 

The above batch process has undergone numerous refinements to improve yields, processing characteristics, purity, and storage stabiUty, but it remains the standard method of manufacture for these products. Recentiy a continuous process has been reported by Bayer AG (6) wherein the condensation is carried out in an extmder. The by-products are removed in a degassing zone, and the molten polymer, mixed with stabilizers, is subsequendy cracked to yield raw monomer. 

Industrial-scale adsorption processes can be classified as batch or continuous (53,54). In a batch process, the adsorbent bed is saturated and regenerated in a cychc operation. In a continuous process, a countercurrent staged contact between the adsorbent and the feed and desorbent is estabhshed by either a tme or a simulated recirculation of the adsorbent. 

Single-Cell Protein. Systems involving single-cell proteins are often very large throughput, continuous processing operations such as the Pmteen process developed by ICI. These are ideal for air-lift bioreactors of which the pressure cycle fermenter is a special case (50). 

There are three types of TAP emissions continuous, intermittent, and accidental. Both routine emissions associated with a batch process or a continuous process that is operated only occasionally can be intermittent sources. A dramatic example of an accidental emission was the release of methyl isocyanate [624-83-9] in Bhopal, India. As a result of this accident, the U.S. Congress created Tide III, a free-standing statute included in the Superfund Amendments and Reauthorization Act (SARA) of 1986. Title III provides a mechanism by which the pubHc can be informed of the existence, quantities, and releases of toxic substances, and requires the states to develop plans to respond to accidental releases of these substances. Eurther, it requires anyone releasing specific toxic chemicals above a certain threshold amount to aimuaHy submit a toxic chemical release form to EPA. At present, there are 308 specific chemicals subject to Title III regulation (37). 

The Biazzi continuous process is also used. The reactants are continuously fed to a series of nitrators at 15—20°C followed by separation of the PETN, water washing, solution in acetone at 50°C, neutralization with gaseous ammonia, and precipitation by dilution with water. The overall yield is more than 95%. The acetone and the spent acid are readily recovered. 

The RDX particle size distribution must be carefully controlled to produce castable slurries of RDX and TNT having acceptable viscosity. Several classes of RDX are produced to satisfy requirements for the various pressed and cast RDX-based compositions. A continuous process for medium-scale production of RDX has been developed by Biazzi based on the Woolwich process (79,151—154). 

Tetiyl. 2,4,6-Trinitrophenylmethylm tramine (tetryl) was used ia pressed form, mostly as a booster explosive and as a base charge ia detonators and blasting caps because of its sensitivity to initiation by primary explosives and its relatively high energy content. Properties are presented ia Table 11 (173). Batch and continuous processes for the production of tetryl have been developed. Tetryl is no longer used ia the United States and has been replaced by RDX (174-178). 

Continuous Solvent—Extrusion Process. A schematic for a typical continuous process, widely used for making solvent propellant for cannons, is shown in Figure 7. This continuous process produces ca 1100 metric tons of single-base propellant per month at the U.S. Army Ammunition Plant (Radford, Virginia). Continuous processes have also been developed for double- and triple-base propellants and for stick as well as granular geometries. A principal aspect of these processes has been the extensive use of single- and double-screw extmders instead of the presses used in the batch process. 

Fig. 7. Continuous process for solvent-extmded single-base propellant (automated single-base line). Vey = conveyor.

D. Mueller, "The Continuous Processing of Gun Propellants by the Twin Screw Extmder," in Proceedings of the Third International Gun Propellant Symposium, Dover, N.J., Oct. 1984. 

D. M. Husband, "A Review of Technology Developments in Continuous Processing of Sohd Propellants (1960—1987)," in Proceedings of 1987 JANNAFPropellant Charactericyition Subcommittee, CPIA Pubhcations, Johns Hopkins University, Laurel, Md., Oct. 1987. 

R. A. McKay,M Study of Selected Parameters in S olid Propellant Processing,]et Propulsion Lab, Pasadena, Calif., Aug. 1986 J. L. Brown and co-workers. Manufacturing Technologyfor SolidPropellantIngredients/Preparation Reclamation, Morton Thiokol, Inc., Brigham City, Utah, Apt. 1985 W. P. Sampson, Eow Cost Continuous Processing of Solid Rocket Propellant, Al-TR-90-008, Astronautics Laboiatoiy/TSTR, Edwards AEB, Oct. 1990. 

Manufacture of Fatty Acids and Derivatives. Splitting of fats to produce fatty acids and glycerol (a valuable coproduct) has been practiced since before the 1890s. In early processes, concentrated alkaU reacted with fats to produce soaps followed by acidulation to produce the fatty acids. Acid-catalyzed hydrolysis, mostly with sulfuric and sulfonic acids, was also practiced. Pressurized equipment was introduced to accelerate the rate of the process, and finally continuous processes were developed to maximize completeness of the reaction (105). Lipolytic enzymes maybe utilized to spHt... 

Processes for Triacetate. There are both batch and continuous process for triacetate. Many of the considerations and support faciUties for producing acetate apply to triacetate however, no acetyl hydrolysis is required. In the batch triacetate sulfuric acid process, however, a sulfate hydrolysis step (or desulfonation) is necessary. This is carried out by slow addition of a dilute aqueous acetic acid solution containing sodium or magnesium acetate (44,45) or triethanolamine (46) to neutrali2e the Hberated sulfuric acid. The cellulose triacetate product has a combined acetic acid content of 61.5%. 

The flow diagram for the viscose process is given in Figure 2. The sequence of reactions necessary to convert cellulose into its xanthate and dissolve it in soda used to be performed batchwise. Fully continuous processes, or mixtures of batch and continuous process stages, are more appropriate for high volume regular viscose staple production. 

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