Preferred route

Acid rhodamines are made by the iatroduction of the sulfonic acid group to the aminoxanthene base. The preferred route is the reaction fluorescein (2) with phosphorous pentachloride to give 3,6-dichlorofluoran (fluorescein dichloride) (23), which is then condensed with a primary aromatic amine in the presence of 2inc chloride and quicklime. This product is then sulfonated. For example, if compound (23) (fluorescein dichloride) is condensed with aniline and the product is sulfonated. Acid Violet 30 Cl45186) (24) is produced. 

Figure 3 shows the production of acetaldehyde in the years 1969 through 1987 as well as an estimate of 1989—1995 production. The year 1969 was a peak year for acetaldehyde with a reported production of 748,000 t. Acetaldehyde production is linked with the demand for acetic acid, acetic anhydride, cellulose acetate, vinyl acetate resins, acetate esters, pentaerythritol, synthetic pyridine derivatives, terephthaHc acid, and peracetic acid. In 1976 acetic acid production represented 60% of the acetaldehyde demand. That demand has diminished as a result of the rising cost of ethylene as feedstock and methanol carbonylation as the preferred route to acetic acid (qv). 

Oxidation. Naphthalene may be oxidized direcdy to 1-naphthalenol (1-naphthol [90-15-3]) and 1,4-naphthoquinone, but yields are not good. Further oxidation beyond 1,4-naphthoquinone [130-15-4] results in the formation of ortho- h. h5 ic acid [88-99-3], which can be dehydrated to form phthaUc anhydride [85-44-9]. The vapor-phase reaction of naphthalene over a catalyst based on vanadium pentoxide is the commercial route used throughout the world. In the United States, the one phthaUc anhydride plant currently operating on naphthalene feedstock utilizes a fixed catalyst bed. The fiuid-bed process plants have all been shut down, and the preferred route used in the world is the fixed-bed process. 

The preferred route to higher purity naphthalene, either coal-tar or petroleum, is crystallisation. This process has demonstrated significant energy cost savings and yield improvements. There are several commercial processes available Sulser-MWB, Brodie type. Bets, and Recochem (37). 

The plutonium extracted by the Purex process usually has been in the form of a concentrated nitrate solution or symp, which must be converted to anhydrous PuF [13842-83-6] or PuF, which are charge materials for metal production. The nitrate solution is sufficientiy pure for the processing to be conducted in gloveboxes without P- or y-shielding (130). The Pu is first precipitated as plutonium(IV) peroxide [12412-68-9], plutonium(Ill) oxalate [56609-10-0], plutonium(IV) oxalate [13278-81-4], or plutonium(Ill) fluoride. These precipitates are converted to anhydrous PuF or PuF. The precipitation process used depends on numerous factors, eg, derived purity of product, safety considerations, ease of recovering wastes, and required process equipment. The peroxide precipitation yields the purest product and generally is the preferred route (131). The peroxide precipitate is converted to PuF by HF—O2 gas or to PuF by HF—H2 gas (31,132). 

Anhydrous aluminum chloride, AIQ, is manufactured primarily by reaction of chlorine [7782-50-5] vapor with molten aluminum and used mainly as a catalyst in organic chemistry ie, in Friedel-Crafts reactions (qv) and in proprietary steps in the production of titanium dioxine [13463-67-7] Ti02, pigment. Its manufacture by carbochlorination of alumina or clay is less energy-intensive and is the preferred route for a few producers (19). 

Production of cyclohexylamine reflects this balance of raw material versus operating cost stmcture. When aniline cost and availabiUty are reasonable, the preferred route is aniline ring reduction alternatively the cyclohexanol amination route is chosen. 

The second major route to diarylamiaes is the condensation of an aromatic amine with a phenol. Aniline [62-53-3] phenol [108-95-2] and 3.5% phosphoric acid at 325°C gives a 50% yield of DPA (23). Apparently, this reaction iavolves the addition of aniline to the keto form of the phenol. Thus, naphthols and hydroquiaone are more reactive and give higher yields of product. This is the preferred route to A/-phenyi-2-naphthyiamiQe, 4-hydroxydiphenyiamiQe, and diphenyl- -phenylenediamine (24). 

Traditionally, this process has been utilized primarily for simple soap bars because it tends to be time-consuming and thus somewhat limited for large-scale bar production. However, advances have been reported in automating this approach (14). Furthermore, the process requires fluid cmtcher compositions for flow into the molds. This typically requires the formulation to contain either a high level of solvents, including water, glycerol, and alcohol, and be at elevated temperatures (>80° C) when poured into the frames. Despite these limitations, it has proven to be the preferred route to producing certain specialty products, for example, transparent bars. 

Vapor-phase oxidation of cyclohexane is commercially feasible, but the preferred route is Hquid-phase cyclohexane oxidation (2). In the latter... 

The oxidation of quinazoline with alkaline permanganate is still the preferred route to pyrimidine-4,5-dicarboxylic acid (04CB3643). 

This section seeks to summarize preferred routes to various types of pyrimidine. To some extent it is based on the personal experience of the present author, who is well aware of its resulting inadequacies. 

The preferred route to quinazoline in quantity is to convert 4-chloro- (748 R = C1) directly into 4-p-toluenesulfonylhydrazinoquinazoline (749) and thence by treatment with... 

Intensification is the preferred route to inherently safer design, as the plants, being smaller, are also cheaper. 

Intensification, when practicable, is the preferred route to inherently safer design, as the reduction in inventory results in a smaller and thus cheaper plant. This is, in addition to the reduction in cost, achieved by reducing the need for added-on protective equipment. 

The fluorination reactions considered so far can be categorized as metathesis, oxidation or substitution, Occasionally reductive fluorination is the preferred route to a lower fluoride. Examples are ... 

The chemistry of thiazoles is interesting in view of their propensity for biological activity. Eor that reason thiazoloquinolines have also been a widely studied group of compounds. A preferred route to thiazoles exploits a-halogeno ketones in a reaction with thioamides to give the fused 2-substituted thiazole derivatives. 

The familiar alkylation of -ketoesters followed by decarboxylation is still a useful route to a-alkyl ketones, although the alkylation of enamines is frequently the preferred route. Given below are two examples of alkylation of 2-carbethoxycycloalkanones (prepared in Chapter 10, Section I). In the first case, sodium ethoxide is the base employed to generate the enolate ion of 2-carbethoxycyclohexanone. In the second case, the less acidic 2-carbethoxycyclooctanone requires sodium hydride for the generation of the enolate ion. 

Benzothiepins 13 and their 2,3-dihydro precursors 12 can be oxidized by two equivalents of 3-chloroperoxybenzoic acid to afford the sulfones 15 and 14, respectively, in moderate to good yields.2,9 83 Sulfones 15 can be prepared using two routes, the reverse order (oxidation, followed by elimination) also being possible (see Section 2.1.2.1. for a description of the elimination reactions). The preferred route must be decided for individual cases. 

Ammonolysis is the preferred route currently in use at the DuPont Company for the depolymerization of nylon-6,6 carpet waste. McKinney13 has described the reaction of nylon-6,6 and nylon-6 mixtures with ammonia at temperatures in the range of 300-350°C at a pressure of about 68 atm in the presence of an ammonium phosphate catalyst to form a mixture of nylon-6,6 and nylon-6 monomers (HMD A, A A, and s-caprolactam) and adiponitrile, 5-cyanovaleramide, 6-aminocapronitrile, and 6-aminocaproamide. 

The principal solvolysis reactions for PET are methanolysis with dimethyl terephthalate and ethylene glycol as products, glycolysis with a mixture of polyols and BHET as products, and hydrolysis to form terephthalic acid and ethylene glycol. The preferred route is methanolysis because the DMT is easily purified by distillation for subsequent repolymerization. However, because PET bottles are copolyesters, the products of the methanolysis of postconsumer PET are often a mixture of glycols, alcohols, and phthalate derivatives. The separation and purification of the various products make methanolysis a cosdy process. In addition to the major product DMT, methanol, ethylene glycol, diethylene glycol, and 1,4-cyclohexane dimethanol have to be recovered to make the process economical.1... 

Delivery of peptides and proteins via the gastrointestinal tract has not been successful because of poor penetration through the intestinal epithelium and high levels of proteolytic activity in the gastrointestinal tract. Liposomal encapsulation of proteins and peptides will not improve the efficiency and capacity of this absorption pathway considerably (e.g., Ryman et al., 1982 Machy and Leserman, 1987 Weiner and Chia-Ming Chiang, 1988). These difficulties in delivery via the oral route caused the parenteral route to remain the preferred route for the administration of therapeutic peptides... 

A surprising exception has been reported with evidence for a cleavage reaction in the case of divinyl sulphone. In non-aqueous and slightly acidic media, the behaviour of a., ji-unsaturated aromatic sulphones is also complex (see Table 7) since the cleavage and the saturation may compete. Strongly electrophilic double bonds undergo Michael additions in aprotic solvents by slowly protonated anions. Transfer of labile hydrogen may also lead to unactivated bases. It is noteworthy that in numerous cases (Table 6) the saturation is the preferred route. 

Subcutaneous (SC) administration of ESA produces a more predictable and sustained response than IV administration, and is therefore the preferred route of administration for both agents. Intravenous administration is often utilized in patients who have established IV access or are receiving hemodialysis. Starting doses of ESAs depend on the patient s Hgb level, the target Hgb level, the rate of Hgb increase and clinical circumstances.31 The initial increase in Hgb should be 1-2 g/dL (0.6206-1.2404 mmol/L) per month. The starting doses of epoetin alfa previously recommended are 80 to 120 units/kg per week for SC administration and 120 to 180 units/kg per week for IV administration, divided two to three times per week. The starting dose of darbepoetin alfa is 0.45 mcg/kg administered SC or IV once weekly (Table 23-3). 

The preferred route of administration is intraperitoneal (IP) rather than IV to achieve maximum concentrations at the site of infection. Antibiotics can be administered IP intermittently as a single large dose in one exchange per day or continuously as multiple smaller doses with each exchange. Intermittent administration requires at least 6 hours of dwell time in the peritoneal cavity to allow for adequate systemic absorption and provides adequate levels to cover the 24-hour period. However, continuous administration is better suited for PD modalities that require more frequent exchanges (less than 6-hour dwell time). The reader should refer to the ISPD guidelines for dosing recommendations for IP antibiotics in CAPD and automated PD patients.49 The dose of the antibiotics should be increased by 25% for patients with residual renal function who are able to produce more than 100 mL urine output per day. 

The intranasal formulation is the preferred route of administration owing to ease of administration and fewer adverse effects, which mainly are local in nature. Adverse effects associated with the intranasal formulation include rhinitis, nasal irritation, and dryness. Hypersensitivity can develop with either formulation and should be considered before administering to patients with a suspected risk of hypersensitivity. 

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