Other Routes

Numerous other, less common routes exist as alternative methods of delivering a drug to the bloodstream. All the routes listed in this section provide drug administration to a part of the body that is heavily perfused with blood vessels and therefore amenable to drug absorption. 

Some olefins can be manufactured industrially by various chemical processes usually employing removal reactions on functional saturated compounds. These specifically involve the dehydration of alcohols and the dehydrochlorination of chlorinated derivatives. 

Production of olefins Br if-PARAfTiN i hydrogenation. Economic data (France conditions, mid-1986) 

T pical process Catofm (Houdry) Oteflex (UOP) PacoLOIcx (UOP) 

6 nCj - 58.1 other C and C - 5.2 Product composition (molar per cent) Gnear ol its 94 tocluding mocKMrie ns 96. 61 Indudiog initial loads. 

The synthesis of ethylene by the dehydration of fennemation ethanol was formerly practised in the industrial countries before the development of steam cracking. This 

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The starting materials for route B are recognisable as the halide we used in frame 41 and an aldehyde easily made by a Diels-Alder reaction. The other route could also be used but the starting materials are not so readily available. Write out the complete synthesis. 

Acetylation of acetaldehyde to ethyUdene diacetate [542-10-9], a precursor of vinyl acetate, has long been known (7), but the condensation of formaldehyde [50-00-0] and acetic acid vapors to furnish acryflc acid [97-10-7] is more recent (30). These reactions consume relatively more energy than other routes for manufacturing vinyl acetate or acryflc acid, and thus are not likely to be further developed. Vapor-phase methanol—methyl acetate oxidation using simultaneous condensation to yield methyl acrylate is still being developed (28). A vanadium—titania phosphate catalyst is employed in that process. 

Other routes to acrylonitrile, none of which achieved large-scale commercial appHcation, are acetaldehyde and HCN (56), propionittile dehydrogenation (57,58), and propylene and nitric oxide (59,60) ... 

Although this first route was simple in concept, it proved slow in operation, difficult to scale up safely, and relatively uneconomical compared with the other routes. Denitration of the fibers, necessary to allow safe use wherever the fabrics may risk ignition, spoiled their strength and appearance. Nevertheless, Chardoimet earned and truly deserved his reputation as the Eather of Rayon. His process was operated commercially until 1949 when the last factory, bought from the Tubize Co. in the United States in 1934 by a Bra2iUan company, burned down. 

Work on other routes to ceUulosic fibers continues, driven by a desire to identify an environmentally benign route to ceUulosic fibers that can utilize the large capital investment in the xanthate route and hence cost less than a completely new fiber process. 

Vlayl fluoride [75-02-5] (VF) (fluoroethene) is a colorless gas at ambient conditions. It was first prepared by reaction of l,l-difluoro-2-bromoethane [359-07-9] with ziac (1). Most approaches to vinyl fluoride synthesis have employed reactions of acetylene [74-86-2] with hydrogen fluoride (HF) either directly (2—5) or utilizing catalysts (3,6—10). Other routes have iavolved ethylene [74-85-1] and HF (11), pyrolysis of 1,1-difluoroethane [624-72-6] (12,13) and fluorochloroethanes (14—18), reaction of 1,1-difluoroethane with acetylene (19,20), and halogen exchange of vinyl chloride [75-01-4] with HF (21—23). Physical properties of vinyl fluoride are given ia Table 1. 

During the 1980s few innovations were disclosed in the Hterature. The hydroxylation of phenol by hydrogen peroxide has been extensively studied in order to improve the catalytic system as well as to master the ratio of hydroquinone to catechol. Other routes, targeting a selective access to one of the dihydroxyben2enes, have appeared. World production capacities according to countries and process types are presented in Table 1. 

Other routes for hydroxybenzaldehydes are the electrolytic or catalytic reduction of hydroxybenzoic acids (65,66) and the electrolytic or catalytic oxidation of cresols (67,68). (see Salicylic acid and related compounds). Sahcylaldehyde is available in drums and bulk quantities. The normal specification is a freezing point minimum of 1.4°C. 4-Hydroxybenzaldehyde is available in fiber dmms, and has a normal specification requirement of a 114°C initial melting point. More refined analytical methods are used where the appHcation requires more stringent specifications. 

Other routes to reachieving filament separation have been described and rely on mechanical or aerodynamic forces to affect separation. Figure 4 illustrates one method which utilizes a rotating deflector plane to force the filaments apart while depositing the opened filaments ia overlapping loops (25). After the splayed filaments fall to the deposition surface or forming screen, a suction from below the disposition surface holds the fiber mass in place. 

Before a 1/1 /70 FDA ban (rescission proposed in early 1990), cyclamate noncaloric sweeteners were the major derivatives driving cycloliexylamine production. The cyclohexylsulfamic acid sodium salt (39) [139-05-9J and mote thermally stable calcium cyclohexylsulfamic acid (40) [139-06-1] salts were prepared from high purity cyclohexylamine by, among other routes, a reaction cycle with sulfamic acid. 

Production is by the acetylation of 4-aminophenol. This can be achieved with acetic acid and acetic anhydride at 80°C (191), with acetic acid anhydride in pyridine at 100°C (192), with acetyl chloride and pyridine in toluene at 60°C (193), or by the action of ketene in alcohoHc suspension. 4-Hydroxyacetanihde also may be synthesized directiy from 4-nitrophenol The available reduction—acetylation systems include tin with acetic acid, hydrogenation over Pd—C in acetic anhydride, and hydrogenation over platinum in acetic acid (194,195). Other routes include rearrangement of 4-hydroxyacetophenone hydrazone with sodium nitrite in sulfuric acid and the electrolytic hydroxylation of acetanilide [103-84-4] (196). 

Trifluoromethanesulfonic acid, also known as triflic acid [1493-13-6] is widely used ia organic syntheses and has been thoroughly reviewed (93,94). It was first prepared ia 1954 via the oxidation of bis(trifluoromethylthio)mercury with hydrogen peroxide [7722-84-1] (95). Several other routes of preparation have been disclosed (96—98). The acid exhibits excellent thermal and hydrolytic stabiUty, it is not readily oxidized or reduced, nor is it prone to fluoride anion generation. 

Many other routes to produce thioglycohc acid have been iavestigated (9). To try to minimise by-products, nucleophilic agents other than alkah sulfhydrates have been claimed, eg, thiosulfates, sodium disulfides, thiourea, xanthogenic acid derivatives, and sodium trithiocarbonates (10). These alternative methods, which require reduction of the disulfides or hydrolysis of carboxymethylthio derivatives, seem less competitive than those usiag alkah sulfhydrates. 

This versatile synthetic route has been used extensively with a great variety of phenols and thiophenols to estabUsh structure—activity relationships for thyromimetic activity. Other routes can be summarized as follows (13). 

The reactants ate fed into the tail flame of a d-c nitrogen plasma. The reaction occurs rapidly at temperatures around 1500°C and the HCl reacts with excess ammonia to form ammonium chloride. Similar reactions have been carried out using furnaces, lasers, and r-f plasmas (34) as the source of heat. Other routes using titanium tetrachloride starting material include... 

A hydrochloric acid process for the manufacture of anatase has been proposed but has not been developed. Other routes include fluoride, bromide, nitrate, sulfide, and chloroacetate processes (1). None of these, however, has been used successfully on a commercial scale. 

A third approach for the synthesis of 6-formylpterin (23) starts from iminodipropionitrile [2869-25-2] (27). The intermediate pyra2ine (28) is also prepared starting from chloropymvaldehyde oxime (41,42). The required formylpterin (23) is obtained in three steps in 71% yield, starting from the intermediate pyra2ine (28). A few other routes for the synthesis of 6-formylpterin (23) are described in the Hterature. AH are multistep procedures with only moderate overall yields (43—45). 

Value is lethal dose low, LD q, the lowest dose of a substance introduced by any other route other than inhalation, over any given period of time and reported to have caused death in humans or animals. 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Other routes to 1,1,2-trichloroethane are chlorination of acetylene in the presence of HCl (101) and chlorination of vinyl chloride at room temperatures with FeCl (102—104), hydrochlorination of cis- and /n j -l,2-dichloroethylene with FeCl catalyst (105), vapor-phase oxychlorination of... 

Other Routes. A unique process that produces vinyl chloride, trichloroethylene, dichloroethane, and trichloroethane simultaneously has been developed by Produits Chemiques Pechiney-Saint-Gobain in France (31). Dichloroethylene is chlorinated directly at low temperature to tetrachloroethane, which is then thermally cracked to give trichloroethylene and hydrochloric acid. The dichloroethylene feed is coproduced with vinyl chloride in a hot chlorination reactor, using chlorine and ethylene as feedstocks. 

In equation 1, the Grignard reagent, C H MgBr, plays a dual role as reducing agent and the source of the arene compound (see Grignard reaction). The Cr(CO)g is recovered from an apparent phenyl chromium intermediate by the addition of water (19,20). Other routes to chromium hexacarbonyl are possible, and an excellent summary of chromium carbonyl and derivatives can be found in reference 2. The only access to the less stable Cr(—II) and Cr(—I) oxidation states is by reduction of Cr(CO)g. 

Other metal chlorides and salts can also be used lea ding to formation of numerous other metal dichloroisocyanurates (34). Other routes to SDCC iuclude reaction of a moistened powdered mixture of TCCA, CA, and NaHCO (35), reaction of cmde CA with NaOCl (36), and reaction of NaH2 with HOCl (37) or CI2O (38). 

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