Formation products

PRODUCT FORMATION Specific product formation rate 

The characteristic parameter for product formation is the specific product formation rate, q. Equations 4.2.31-4.2.34 and the methods of analysis introduced for metabolic byproducts also apply to secreted protein products. 

The general formula for for batch growth in a stirred vessel is given by Equation 4.2.32, where P is the extracellular product concentration. Frequently, q is relatively constant during batch growth. One example is monoclonal antibody production by hybridoma cells (Renard et al, 1988). If it is assumed that q does not vary with time, then Equation 4.2.32 can be integrated to yield Equation 4.2.45  

Reactors may be operated with product retention as well as cell retention. This allows for product recovery at high concentration. Retention may be accomplished by using a membrane with a pore size that is too small to allow passage of product but large enough to allow passage of metabolites and waste products. Capsules that retain cells can also retain product. In any type of product-retention system, retention may not be 100%. This does not complicate analysis as long as the 

We can define an apparent yield of product from substrate (Fps) as a measure of the efficiency of product formation that can be used to compare cells grown in different culture systems or in different media. Product P is a cellular product such as monoclonal antibody, while substrate S may be serum, glucose, glutamine, oxygen or any other important substrate. Analysis of the overall yield (from endpoint calculations) may allow for comparison of production efficiency between different reactors and culture conditions. Analysis of the yield at various time points allows for detection of changes in the mechanisms of product formation. Product yields are useful in identifying product degradation in culture (as evidenced by a decrease in Ypg for aU substrates). 

Microbial products may be formed as a result of a variety of processes which occur within the cells of a microbial culture. In some cases the cell itself may be the desired product, or it may be that the product is formed as the direct consequence of its growth. There is in the latter circumstances a direct link between growth and the accumulation of product. However, there are many important microbial products which are not growth-associated, where there may exist mechanisms within the cells, as outlined in Section S.S.2, which operate to produce a particular material only under certain special circumstances. As a result, the yield coefficient Yr,s is of little value in predicting the course of product accumulation, except when the overall productivity of a complete batch operation is considered. 

Gaden(54) proposed a scheme which grouped fermentations according to the manner in which the microbial product appeared in the broth (Table 5.18). Whilst this is simpler than that put forward later by Deindoerfer 55), it does form an useful basis from which to develop a quantitative description of the process. 

1 Product formation is directly related to carbohydrate utilisation Ethanol 

2 Product formation indirectly related to carbohydrate utilisation Citric acid 

3 Product formation apparently not associated with carbohydrate utilisation Penicillin 

---

The economic tradeoffs now become more complex, and a new cost must be added to the tradeoffs. This is a raw material efficiency cost due to byproduct formation. If the PRODUCT formation is kept constant despite varying levels of BYPRODUCT formation, then the cost can be defined to be ... 

The value of PRODUCT formation and the raw materials cost of FEED that reacts to PRODUCT are constant. Alternatively, if the byproduct has no value, the cost of disposal should be included as... 

Tannor D J and Rice S A 1988 Coherent pulse sequence control of product formation in chemical reactions Adv. Chem. Rhys. 70 441 -524... 

Transesterification of a lower acrylate ester and a higher alcohol (102,103) can be performed using a variety of catalysts and conditions chosen to provide acceptable reaction rates and to minimize by-product formation and polymerization. 

The main intermediates in the pentaerythritol production reaction have been identified and synthesized (50,51) and the intermediate reaction mechanisms deduced. Without adequate reaction control, by-product formation can easily occur (52,53). Generally mild reaction conditions are favored for optimum results (1,54). However, formation of by-products caimot be entirely eliminated, particularly dipentaerytbritol and the linear formal of pentaerythritol, 2,2 -[meth5lenebis(oxymethylene)]bis(2-hydroxymethyl-1,3-propanediol) [6228-26-8] ... 

A typical flow diagram for pentaerythritol production is shown in Figure 2. The main concern in mixing is to avoid loss of temperature control in this exothermic reaction, which can lead to excessive by-product formation and/or reduced yields of pentaerythritol (55,58,59). The reaction time depends on the reaction temperature and may vary from about 0.5 to 4 h at final temperatures of about 65 and 35°C, respectively. The reactor product, neutralized with acetic or formic acid, is then stripped of excess formaldehyde and water to produce a highly concentrated solution of pentaerythritol reaction products. This is then cooled under carefully controlled crystallization conditions so that the crystals can be readily separated from the Hquors by subsequent filtration. 

Certain factors and product precursors are occasionally added to various fermentation media to iacrease product formation rates, the amount of product formed, or the type of product formed. Examples iaclude the addition of cobalt salts ia the vitamin fermentation, and phenylacetic acid and phenoxyacetic acid for the penicillin G (hen ylpenicillin) and penicillin V (phenoxymethylpenicillin) fermentations, respectively. Biotin is often added to the citric acid fermentation to enhance productivity and the addition of P-ionone vastly iacreases beta-carotene fermentation yields. Also, iaducers play an important role ia some enzyme production fermentations, and specific metaboHc inhibitors often block certain enzymatic steps that result in product accumulation. 

Second International Congress on Toxic Combustion By-Products Formation and Control, Salt Lake City, Utah, Mar. 26—29,1991. 

The solvent, magnesium, and RX can have a deleterious effect on the preparation of the Grignard reagent. Some of the problems are a homocoupled product, formation of RMg02X, and noniaitiated reaction of RX with Mg. Therefore, proper preparation and handling of each component must be carried out. 

An excess of phosgene is used during the initial reaction of amine and phosgene to retard the formation of substituted ureas. Ureas are undesirable because they serve as a source for secondary product formation which adversely affects isocyanate stabiUty and performance. By-products, such as biurets (23) and triurets (24), are formed via the reaction of the labile hydrogens of the urea with excess isocyanate. Isocyanurates (25, R = phenyl, toluyl) may subsequendy be formed from the urea oligomers via ring closure. 

Commercially important arenesulfonyl isocyanates are not directly accessible from the corresponding sulfonamides via phosgenation due to lack of reactivity or by-product formation at elevated temperatures. A convenient method for their preparation consists of the reaction of alkyl isocyanates with sulfonamides to produce mixed ureas which, upon phosgenation, yield a mixture of alkyl and arenesulfonyl isocyanates. The desired product can be obtained by simple distillation (16). Optionally, the oxalyl chloride route has been employed for the synthesis of arenesulfonyl isocyanate (87). 

Compression. Compression is the simplest and the least effective of the four recovery methods. It was the first process used for the recovery of hydrocarbon Hquids from natural gas but is used only ia isolated cases. The most significant appHcation of the compression process is for gas-cycling plants where the natural gas Hquids are removed and the remaining gas is returned to the production formation. Figure 3 is a schematic of a typical gas-cycle plant. 

The zinc oxide component of the catalyst serves to maintain the activity and surface area of the copper sites, and additionally helps to reduce light ends by-product formation. Selectivity is better than 99%, with typical impurities being ethers, esters, aldehydes, ketones, higher alcohols, and waxes. The alumina portion of the catalyst primarily serves as a support. 

Selectivity is primarily a function of temperature. The amount of by-products tends to increase as the operating temperature is raised to compensate for declining catalyst activity. By-product formation is also influenced by catalyst impurities, whether left behind during manufacture or otherwise introduced into the process. Alkaline impurities cataly2e higher alcohol production whereas acidic impurities, as well as trace iron and nickel, promote heavier hydrocarbon formation. 

Stea.m-Ra.ising Converter. There are a variety of tubular steam-raising converters (Fig. 7d) available, which feature radial or axial flow, with the catalyst on either shell or tube side. The near-isothermal operation of this reactor type is the most thermodynamically efficient of the types used, requiring the least catalyst volume. Lower catalyst peak temperatures also result in reduced by-product formation and longer catalyst life. 

Calcite and siderite (27) are used occasionally because of their solubiUty in hydrochloric acid which offers a method of removing mud filter cake deposited on productive formations. Calcite and siderite are used most frequently in workover or completion fluids when a nondamaging fluid is required, ie, one that can be removed by acidising at a later time. 

Some phosphides, such as titanium phosphide [12037-65-9] TiP, can be prepared bypassing phosphine over the metal or its haUde. Reaction of phosphine with heavy metal salt solutions often yields phosphines that may contain unsubstituted hydrogens. Phosphides may also be prepared by reducing phosphoms-containing salts with hydrogen, carbon, etc, at high temperatures, the main example of which is the by-product formation of ferrophosphoms in the electric furnace process for elemental phosphoms. Phosphoms-rich phosphides such as vanadium diphosphide [12037-77-3] may be converted to lower phosphides, eg, vanadium phosphide [12066-53-4] by thermal treatment. 

Ethylbenzene Hydroperoxide Process. Figure 4 shows the process flow sheet for production of propylene oxide and styrene via the use of ethylbenzene hydroperoxide (EBHP). Liquid-phase oxidation of ethylbenzene with air or oxygen occurs at 206—275 kPa (30—40 psia) and 140—150°C, and 2—2.5 h are required for a 10—15% conversion to the hydroperoxide. Recycle of an inert gas, such as nitrogen, is used to control reactor temperature. Impurities ia the ethylbenzene, such as water, are controlled to minimize decomposition of the hydroperoxide product and are sometimes added to enhance product formation. Selectivity to by-products include 8—10% acetophenone, 5—7% 1-phenylethanol, and <1% organic acids. EBHP is concentrated to 30—35% by distillation. The overhead ethylbenzene is recycled back to the oxidation reactor (170—172). 

Primary and secondary amines are usually converted to tertiary amines using formaldehyde and hydrogen in the presence of a catalyst (eqs. 5 and 6). This process, known as reductive alkylation (222), is attractive commercially. The desired amines are produced in high yields and without significant by-product formation. Quatemization by reaction of an appropriate alkylating reagent then follows. 

Technetium-99m disofenin is used for hepatobiliary imaging. Disofenin (2,6-diisopropylphenylcarbamoyhnethyliminodiacetic acid) is the active ingredient. Product formation is accompHshed by addition of up to 3.7 GBq (100 mCi) of Tc pertechnetate. 

Synthetic pine oil is produced by the acid-catalyzed hydration of a-pinene (Fig. 1). Mineral acids, usually phosphoric acid, are used in concentrations of 20—40 wt % and at temperatures varying from 30—100°C. Depending on the conditions used, alcohols, chiefly a-terpineol (9), are produced along with /)-menthadienes and cineoles, mainly limonene, terpinolene, and 1,4- and 1,8-cineole (46—48). Various grades of pine oil can be produced by fractionation of the cmde products. Formation of terpin hydrate (10) from a-terpineol gives P-terpineol (11) and y-terpineol (12) as a consequence of the reversible... 

Oxychlorination reactor feed purity can also contribute to by-product formation, although the problem usually is only with low levels of acetylene which are normally present in HCl from the EDC cracking process. Since any acetylene fed to the oxychlorination reactor will be converted to highly chlorinated C2 by-products, selective hydrogenation of this acetylene to ethylene and ethane is widely used as a preventive measure (78,98—102). 

For the maximum level, 5% or more of carbon substrate is consumed by yeast growth and by-product formation. 

Enzyme Immunosensors. Enzyme immunosensors are enzyme immunoassays coupled with electrochemical sensors. These sensors (qv) require multiple steps for analyte determination, and either sandwich assays or competitive binding assays maybe used. Both of these assays use antibodies for the analyte of interest attached to a membrane on the surface of an electrochemical sensor. In the sandwich assay type, the membrane-bound antibody binds the sample antigen, which in turn binds another antibody that is enzyme-labeled. This immunosensor is then placed in a solution containing the substrate for the labeling enzyme and the rate of product formation is measured electrochemically. The rate of the reaction is proportional to the amount of bound enzyme and thus to the amount of the analyte antigen. The sandwich assay can be used only with antigens capable of binding two different antibodies simultaneously (53). 

---