Large scale preparation

Vigorous mechanical stirring is preferable, particu. larly for large.scale preparations a three-necked flask should be used. Thus for a preparation on four times the above scale, the addition of 120 g. (147 ml.) of sec.-... 

In large scale preparations, the mixtine should be transferred to a large flask before heating. 

For large scale preparations use a tliree-necked flask equipped with two reflux condensers and an oil-sealed stirrer. 

A small quantity of mandelonitrild may be obtained by extracting the aqueous layer with 25 ml. of benzene, evaporating the benzene, and adding the residue to the main portion. This extraction is hardly worth while except for large scale preparations. 

Acetylene was discovered m 1836 by Edmund Davy and characterized by the French chemist P E M Berthelot m 1862 It did not command much attention until its large scale preparation from calcium carbide m the last decade of the nineteenth century stim ulated interest m industrial applications In the first stage of that synthesis limestone and coke a material rich m elemental carbon obtained from coal are heated m an electric furnace to form calcium carbide... 

Although these humble origins make interesting historical notes m most cases the large scale preparation of carboxylic acids relies on chemical synthesis Virtually none of the 3 X 10 lb of acetic acid produced m the United States each year is obtained from vinegar Instead most industrial acetic acid comes from the reaction of methanol with carbon monoxide... 

Thus the large-scale preparation of pyridoxylated hemoglobin seems to result in mixtures of reaction products. These probably represent modifications at either or both a- and P-antino-terrmnal residues as well as surface lysines. A partial characterization of the mixture has been carried out (74). 

Me3SiCHN2, MeOH, benzene, 20°. This reagent does not react with phenols This is a safe alternative to the use of diazomethane. A detailed, large-scale preparation of this useful reagent has been described. ... 

This method for the preparation of cyclobutanone via oxaspiropentane is an adaptation of that described by Salaiin and Conia. The previously known large-scale preparations of cyclobutanone consist of the reaction of the hazardous diazomethane with ketene, the oxidative degradation or the ozonization in presence of pjrridine of methylenecyclobutane prepared from pentaerythritol, or the recently reported dithiane method of Corey and Seebach, which has the disadvantage of producing an aqueous solution of the highly water-soluble cyclobutanone. A procedure involving the solvolytic cyclization of 3-butyn-l-yl trifluoro-methanesulfonate is described in Org. Syn., 54, 84 (1974). 

The procedure described here is a large-scale preparation with satisfactory yields of a still very expensive but simple compound from very cheap and readily available starting materials and with ordinary laboratory equipment. This rearrangement of oxaspiropentanes into cyclobutanones appears to be general for the preparation of substituted cyclobutanones. ... 

All of these methods provide only moderate yields of 17-keto steroids, but some [particularly (b)] have been considered for large scale preparative work. The advent of superior methods now limits the above procedures to structure proof and degradative studies. 

Anhydrous sulfuric acid is a dense, viscous liquid which is readily miscible wilh water in all proportions the reaction is extremely exothermic ( 880kJmol at infinite dilution) and can result in explosive spattering of the mixture if the water is added to the acid it is therefore important always to use the reverse order and add the acid to the water, slowly and with stirring. The large-scale preparation of sulfuric acid is a major industr) in most countries and is described in the preceding Panel. 

However, the unpredictably explosive nature of CI2O in the liquid state renders this process somewhat hazardous and the best large-scale preparation is the low-temperature fluorination of CIONO2 (p. 884) ... 

Treatment of 4-hydroxy-l-phenyl-l,8-naphthyridin-2-(lH)-one (76) with sodium nitrite gave the 3-nitroso derivative (77), which could be oxidized to 4-hydroxy-3-nitro-l-phenyl-l,8-naphthyridin-2(lH)-one (30a) (94SC3289). According to the authors, this method of preparing (30a) is more convenient for large-scale preparation than the one using A-phenyl-3-azaisatoic anhydride as starting material (see Section II,A,4,a) [(29a) (30a)]. 

This method has been applied to a large-scale preparation of 6-bromoindole, which reacts with various arylboronic acids via the Suzuki reaction to afford 6-aryhndoles fEq. 10.50. 6-Bromo-5-methoxyindole for use in the synthesis of marine bromoindole " and 5-amino-7-ethoxycarbonyhndole for use in synthesis of l//-pyrrolo[3,2-g quina2ohne ring system fEq. 10.51 " have been prepared from the appropriate o-nitrotoluene. 

The synthetic problem is now reduced to the development of a feasible, large-scale preparation of enantiomerically pure (/ )-citro-nellal (36), which has a single stereogenic center. One way in which the aldehyde function in 36 could be introduced is through the hydrolysis of a terminal enamine. (/ )-CitronelIal (36) can thus be traced to citronellal ( )-diethylenamine (44), the projected product of an enantioselective isomerization of prochiral diethylgera-... 

Method B (More suitable for large-scale preparations).41 A solution of benzene-1,2-diacetonitrile (19 18 g, 0.115 mol) in HOAc (30 mL) was added dropwise to a stirred 30 % solution (72 g) of HBr in HOAc. After 2 h the benzazepinium hydrobromide was collected by filtration and the residue washed successively with HOAc and Et20, and then dried. A solution of the hydrobromide salt (28 g) in DMF (100 mL) was added dropwise with stirring to sat. aq NaHC03 (500 mL), and the resulting mixture filtered. The residue was washed with H20, and then dried to give the crude product which was crystallized (EtOAc) yield 16g (61 %) mp -lOS C. 

The generality of this method for large-scale preparations was demonstrated for the syntheses of toluenesulfonyl aziridines from aminohydroxylation products of N-substituted cinnamamides (Table 12.9). The results of synthesis of other sulfo-nyl aziridines are summarized in Tables 12.10 and 12.11. 

This procedure, in contrast to previous methods, comprises only one step and is readily adapted to large-scale preparative work. Furthermore dibromination is very slow in methanol and hence the crude reaction products contain only traces of dibromo ketones. This contrasts with the behavior in other solvents such as ether or carbon tetrachloride, where larger amounts of dibromo ketones are always present, even when one equivalent of bromine is used. Methanol is thus recommended as a brominating solvent even when no orientation problem is involved. It should be noted that a-bromomethyl ketals are formed along with x-bromoketones and must be hydrolyzed during the workup (Note 8).7... 

Mullins, L.J. Leary, J.A. Bjorkland, C.W. "Large Scale Preparation of High Purity Plutonium Metal by Electrorefining", Los Alamos Nat. Lab. report LAMS-2441 (1960). 

Ethane-1-hydroxy-1,1-diphosphonic acid is a substance widely used as a sequestering agent. Hence there are many methods developed for its large-scale preparation [106,107]. The substance was known as early as 1865 [79]. 

In the presence of a precious metal catalyst, aryl halides can undergo dehalo-dimerization to give biaryl products, with varying degrees of selectivity. The major byproduct of this reaction is usually the dehalogenated aryl compound. This type of chemistry is currently one of the very few viable means for the large scale preparation of biaryl compounds. 

Since the late 1940s, NCA polymerizations have been the most common technique used for large scale preparation of high molecular weight polypeptides [13]. However, these materials have primarily been homopolymers, random copolymers, or graft copolymers that lack the sequence specificity and monodispersity of natural... 

In Table 2, the properties and characteristics of the five HNLs presently applied in the enzyme-catalyzed large-scale preparation of chiral cyanohydrins are summarized. ... 

The strategy for preparing gold catalysts for liquid-phase oxidation is based on environment friendly and cheap methodologies with the aim to produce 3-5 nm particles, well dispersed on carbon supports, to be applied also to large-scale preparations. 

Figure 3. Particle size distribution of the gold particles after deposition in the large-scale preparation on (A) X40S and (B) XC72R.

Figure 4. Catalytic activity of the Au/C large-scale preparations and the 2g preparation in glucose oxidation. Reaction conditions glucose 50wt.% S/M ratio 20,000 O2 flow INL/min stirring rate 1700rpm. pH 9.5.

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