Raw material synthesis

Raw Materials. Synthesis gas and an olefin are the reactants of the Oxo process. The ratio of H CO is usually 1 1. Although equal molar quantities of synthesis gas and olefin are consumed, normally an excess of synthesis gas is used. 

The presence of residual solvents (RS) in pharmaceutical substances occurs for various reasons. Solvents are involved in all steps of raw material synthesis and pharmaceutical productions. The search for the presence of RS in a pharmaceutical product and then-concentrations are now mandatory in any new monographs (as detailed in Chapter 16.2). 

Many publications dealing with TLC/HPTLC steroid analysis have appeared every year. The publications can be summarized into categories as follows analytical control of steroid formulations (drug preparations), determination of steroids in biological media and natural resources, and analytical control of the production of steroids (including raw material, synthesis, and biotransformation). A cumulative database of thousands of TLC methods (including steroids) is provided in compact-disk (CD) format by Camag. ... 

Commercial production of acetic acid has been revolutionized in the decade 1978—1988. Butane—naphtha Hquid-phase catalytic oxidation has declined precipitously as methanol [67-56-1] or methyl acetate [79-20-9] carbonylation has become the technology of choice in the world market. By-product acetic acid recovery in other hydrocarbon oxidations, eg, in xylene oxidation to terephthaUc acid and propylene conversion to acryflc acid, has also grown. Production from synthesis gas is increasing and the development of alternative raw materials is under serious consideration following widespread dislocations in the cost of raw material (see Chemurgy). 

Historically, the use of acetylene as raw material for chemical synthesis has depended strongly upon the avadabihty of alternative raw materials. The United States, which until recendy appeared to have limitless stocks of hydrocarbon feeds, has never depended upon acetylene to the same extent as Germany, which had more limited access to hydrocarbons (1). During Wodd War 1 the first manufacture of a synthetic mbber was undertaken ia Germany to replace imported natural mbber, which was no longer accessible. Acetylene derived from calcium carbide was used for preparation of... 

Ethylene Cyanohydrin Process. This process, the fkst for the manufacture of acryhc acid and esters, has been replaced by more economical ones. During World War I, the need for ethylene as an important raw material for the synthesis of ahphatic chemicals led to development of this process (16) in both Germany, in 1927, and the United States, in 1931. 

Because of the high costs of raw materials and the relatively complex synthesis, the 2-cyanoacryhc esters are moderately expensive materials when considered in bulk quantities. Depending on the quantity and the specific ester or formulation involved, the prices for cyanoacryhc ester adhesives can range from approximately 30/kg to over 1000/kg. For these reasons, as weU as several technical factors related to handling and performance, cyanoacryhc ester adhesives are best suited to small bonding apphcations, very often where single drops or small beads are adequate for bonding. In such cases the cost of the adhesive becomes inconsequential compared to the value of the service it performs, and these adhesives become very economical to use. 

Isobutyl alcohol [78-83-1] forms a substantial fraction of the butanols produced by higher alcohol synthesis over modified copper—zinc oxide-based catalysts. Conceivably, separation of this alcohol and dehydration affords an alternative route to isobutjiene [115-11 -7] for methyl /-butyl ether [1624-04-4] (MTBE) production. MTBE is a rapidly growing constituent of reformulated gasoline, but its growth is likely to be limited by available suppHes of isobutylene. Thus higher alcohol synthesis provides a process capable of supplying all of the raw materials required for manufacture of this key fuel oxygenate (24) (see Ethers). 

The technology of urea production is highly advanced. The raw materials requited ate ammonia and carbon dioxide. Invariably, urea plants ate located adjacent to ammonia production faciUties which conveniently furnish not only the ammonia but also the carbon dioxide, because carbon dioxide is a by-product of synthesis gas production and purification. The ammonia and carbon dioxide ate fed to a high pressure (up to 30 MPa (300 atm)) reactor at temperatures of about 200°C where ammonium carbamate [111-78-0] CH N202, urea, and water ate formed. 

Resources for Nitrogen Fertilizers. The production of more than 95% of all nitrogen fertilizer begins with the synthesis of ammonia, thus it is the raw materials for ammonia synthesis that are of prime interest. Required feed to the synthesis process (synthesis gas) consists of an approximately 3 1 mixture (by volume) of hydrogen and nitrogen. 

Apart from the cleanout procedure, the analytical work performed during the production of a bulk pharmaceutical in a three-step synthesis includes 15 different analyses having deterrnination of 22 parameters for raw materials 15 different analyses having deterrnination of 17 parameters in process controls and 11 different analyses having deterrnination of 19 parameters for the product. 

Historically, formaldehyde has been and continues to be manufactured from methanol. EoUowing World War II, however, as much as 20% of the formaldehyde produced in the United States was made by the vapor-phase, noncatalytic oxidation of propane and butanes (72). This nonselective oxidation process produces a broad spectmm of coproducts (73) which requites a complex cosdy separation system (74). Hence, the methanol process is preferred. The methanol raw material is normally produced from synthesis gas that is produced from methane. 

Methane. As our most abundant hydrocarbon, methane offers an attractive source of raw material for organic chemicals (see Hydrocarbons). Successful commercial processes of the 1990s are all based on the intermediate conversion to synthesis gas. An alternative one-step oxidation is potentially very attractive on the basis of simplicity and greater energy efficiency. However, such processes are not yet commercially viable (100). 

Acetylene is used primarily as a raw material for the synthesis of a variety of organic chemicals (see AcETYLENE-DERiVED CHEMICALS). In the United States, this accounts for about 80% of acetylene usage and most of the remainder is used for metal welding or cutting. The chemical markets for acetylene are shrinking as ways are found to substitute lower cost olefins and paraffins for the acetylene, with some products now completely derived from olefinic starting materials. Metalworking appHcations, however, have held up better than chemical uses. 

Synthesis. Because of the limited availabiUty of by-product isoprene much effort has been devoted to synthesis of isoprene. Most routes tend to have marginal selectivity and require large amounts of energy. The choice of which route is preferable depends on availabiUty and cost of raw materials and cost of energy. Several synthetic routes have been practiced commercially (103—108). 

Diketones ate used for extraction and identification of metals, and as raw materials for synthesis of heterocycHc compounds. The abiUty of... 

Hexanedione [110-13-4] (acetonylacetone) is one of the most widely used 1,4-diketones. It is a colorless high boiling Hquid prepared by the hydrolysis of 2,5-dimethylfuran (332,333), by oxidation of 2,5-hexanediol (334) or 5-hexen-l-one (335), and from allylacetone (336). Its main use is in solvent systems and as a raw material for chemical synthesis. It is reportedly not highly toxic (336). 

A typical material balance as well as chemical compositions are given in Table 5. The raw materials are metered into the makeup tanks in the proper ratios. Crysta11i2ation takes place in a separate crysta11i2er. An intermediate aging step at ambient temperature may be requited for the synthesis of certain high purity 2eobtes. 

Nitromethane. The nitroparaffins are used widely as raw materials for synthesis. Nitromethane is used to produce the nitro alcohol (qv) 2-(hydroxymethyl)-2-nitro-l,3-propanediol, which is a registered biocide useful for control of bacteria in a number of industrial processes. This nitro alcohol also serves as the raw material for the production of the alkanolamine (qv) 2-amino-2-(hydroxymethyl)-l,3-propanediol, which is an important buffering agent useful in a number of pharmaceutical appHcations. 

Nitroethane. The principal use of nitroethane is as a raw material for synthesis in two appHcations. It is used to manufacture a-methyl dopa, a hypertensive agent. Also, the insecticide 3 -methyl-A/-[(methylcarbamoyl)oxy]thioacetimidate [16752-77-5] can be produced by a synthesis route using nitroethane as a raw material. The first step of this process involves the reaction of the potassium salt of nitroethane, methyl mercaptan, and methanol to form methyl methylacetohydroxamate. Solvent use of nitroethane is limited but significant. Generally, it is used in a blend with 1-nitropropane. 

Synthesis. Exploratory research has produced a wide variety of odorants based on natural stmctures, chemicals analogous to naturals, and synthetic materials derived from available raw materials and economical processing. As in most areas of the chemical industry, the search for new and useful substances is made difficult by the many materials that have been patented and successfully commercialized (4). In the search for new aroma chemicals, many new materials are prepared for screening each year. Chemists who perform this work are involved in a creative exercise that takes its direction from the commercial sector in terms of desirable odor types and specific performance needs. Because of economic limitations, considerations of raw material costs and available processing methods may play a role eady in the exploratory work. 

Alkylated phenol derivatives are used as raw materials for the production of resins, novolaks (alcohol-soluble resins of the phenol—formaldehyde type), herbicides, insecticides, antioxidants, and other chemicals. The synthesis of 2,6-xylenol [576-26-1] h.a.s become commercially important since PPO resin, poly(2,6-dimethyl phenylene oxide), an engineering thermoplastic, was developed (114,115). The demand for (9-cresol and 2,6-xylenol (2,6-dimethylphenol) increased further in the 1980s along with the growing use of epoxy cresol novolak (ECN) in the electronics industries and poly(phenylene ether) resin in the automobile industries. The ECN is derived from o-cresol, and poly(phenylene ether) resin is derived from 2,6-xylenol. 

Organoaluminum Compounds. Apphcation of aluminum compounds in organic chemistry came of age in the 1950s when the direct synthesis of trialkylalurninum compounds, particularly triethylalurninum and triisobutylalurninum from metallic aluminum, hydrogen, and the olefins ethylene and isobutylene, made available economic organoalurninum raw materials for a wide variety of chemical reactions (see a-BONDED alkyls and aryls). 

An estimation of the amount of amino acid production and the production methods are shown ia Table 11. About 340,000 t/yr of L-glutamic acid, principally as its monosodium salt, are manufactured ia the world, about 85% ia the Asian area. The demand for DL-methionine and L-lysiae as feed supplements varies considerably depending on such factors as the soybean harvest ia the United States and the anchovy catch ia Pern. Because of the actions of D-amiao acid oxidase and i.-amino acid transamiaase ia the animal body (156), the D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is iaexpensively produced by chemical synthesis is primarily used as a feed supplement. In the United States the methionine hydroxy analogue is partially used ia place of methionine. The consumption of L-lysiae has iacreased ia recent years. The world consumption tripled from 35,000 t ia 1982 to 100,000 t ia 1987 (214). Current world consumption of L-tryptophan and i.-threonine are several tens to hundreds of tons. The demand for L-phenylalanine as the raw material for the synthesis of aspartame has been increasing markedly. 

Aspartame (L-aspartyl-L-phenylalanine methyl ester [22839-47-0]) is about 200 times sweeter than sucrose. The Acceptable Daily Intake (ADI) has been estabUshed by JECFA as 40 mg/kg/day. Stmcture-taste relationship of peptides has been reviewed (223). Demand for L-phenylalanine and L-aspartic acid as the raw materials for the synthesis of aspartame has been increasing, d-Alanine is one component of a sweetener "Ahtame" (224). 

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