Gram-scales

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

That work led to a routine 700 gram scale oxide reduction process that has been in use since that time. Recent development work at LANL has increased the batch size to one kilogram of oxide feed. It appears that the ultimate limitation on DOR batch size will be from criticality safety constraints. 

With L-glyceraldehyde as substrate, the same extract catalyzed a half-gram scale synthesis of 1 -deoxy-L-f/ueo-pentulose. 

In the laboratory, preparative electrolyses on the one gram scale can readily be carried out in simple three-electrode cells. The connection of such a cell to a typical potentiostat (feedback system) is illustrated in Fig. 15. It is normally desirable that the electrolysis should be carried out at constant temperature and potential and at a high rate. Hence when designing such cells it is necessary to consider a number of factors. These include the following. 

Under the appropriate conditions, Ge(CF3)4 is obtained from Ge(CH3)4 in 63% yield, on a three-gram scale. 

This thermodynamic driving force is particularly useful tvith multienzyme equilibrium systems such as that used in the gram-scale synthesis of tv ro equivalents ofo-xylulose 5-phosphate (104) from (26) (Figure 10.38) [171,172]. Similarly, the corresponding 1-deoxy-D-xylulose 5-phosphate tvas efficiently produced from pyruvate and (34) by the catalytic action of the thiamine diphosphate-dependent 1-deoxy-D-xylulose 5-phosphate synthase (DXS) (EC 2.2.1.7) from E. coli [173]. 

Chlorinated dibenzo-ip-dioxins were prepared on the gram scale for use as toxicological standards, 2,7-Dichlorodi-henzo-p-dioxin was prepared by catalytic condensation of potassium 2-bromo-4-chlorophenate in 70% yield. Thermal condensation of the potassium salt of 2,4,4 -trichloro-2 -hydroxy diphenyl ether gave a mixture of the 2,8- and 2,7-dichlorodibenzo-p-dioxins which were separated by fractional recrystallization. 2,3,7,8-T etrachlorodibenzo-p-dioxin of 99.9- -% purity was prepared by catalytic condensation of potassium 2,4,5-trichlorophenate. An isomeric mixture of hexachlorodibenzo-p-dioxins was prepared by pyrolytic condensation of sodium 2,3,4,6-tetrachlorophenate. Chlorination of pentachlorophenol (containing < 0.07% tetrachlorophenol) in trichlorobenzene gave octachlorodi-benzo-p-dioxin in 80% yield contaminated by 5-15% heptachlorodibenzo-p-dioxin. Oxidative methods were used to produce octachlorodibenzo-p-dioxin at 99.9% purity. 

The preparation of 2,3,7,8-tetrachlorodibenzo-p-dioxin by chlorination of 2,7-dichlorodibenzo-p-dioxin yields a product containing significant quantities of trichloro- and pentachlorodibenzo-p-dioxins (11). Such mixtures are not amenable to separation on a preparative scale. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin has been prepared by the pyrolytic condensation of sodium 2,4,5-trichlorophenate, this method is undesirable for preparation of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the gram scale (2, 12). The pyrolytic reaction is difficult to control and the potential danger is enhanced by the product s toxicity. The salt was dissolved in bEEE [bis(2-ethoxyethyl) ether, bp 189°-190°C] and refluxed for 15 hours with the Ullmann catalyst. The desired product was obtained in 39% yield by condensation of potassium 2,4,5-trichlorophenate (Reaction 3). 

Jacobsen and co-workers also described the highly enantioselective hydrocyanation of ketimines with the urea analogue. After recrystallisation of the corresponding Strecker adduct, formylation and hydrolysis, the N-benzyl R-methylphenylglycine, was obtained. The R-amino acid hydrochloride is obtained in 93% overall yield with > 99.9% ee on a gram scale [149]. 

Dendrons 21-23 are easily prepared on a multi-gram scale and are highly soluble in common organic solvents thanks to the presence of the four long alkyl chains per peripheral fullerene unit. Therefore, they appear to be good candidates for the preparation of fullerene-rich macromolecules, for example, as shown by their attachment to a phenanthroline diol derivative and the preparation of the corresponding copper(I) complexes (see below). 

Electric-field-directed growth of gold nanorods in aqueous surfactant solutions. Advanced Functional Materials, 14, 571-579 (d) Jana, N.R. (2005) Gram-scale synthesis of soluble, near-monodisperse gold nanorods and other anisotropic nanoparticles. Small,... 

Smith, A.B. Ill, Beauchamp, T.J., LaMarche, M.J. etal. (2000) Evolution ofa Gram-Scale Synthesis of (-F)-Discodermolide. Journal of the American Chemical Society, 122, 8654-8664. 

Schmid, A., Hofstetter, K., Feiten, H.J., Holhnann, R, Witholt, B. (2001) Integrated Biocatalytic Synthesis on Gram Scale The Highly Enantio Selective Preparation of Chiral Oxiranes with Styrene Monooxygenase. Advanced Synthesis Catalysis, 343(6-7), I il-l il. 

There is a wide variety of commercially available chiral stationary phases and mobile phase additives.32 34 Preparative scale separations have been performed on the gram scale.32 Many stationary phases are based on chiral polymers such as cellulose or methacrylate, proteins such as human serum albumin or acid glycoprotein, Pirkle-type phases (often based on amino acids), or cyclodextrins. A typical application of a Pirkle phase column was the use of a N-(3,5-dinitrobenzyl)-a-amino phosphonate to synthesize several functionalized chiral stationary phases to separate enantiomers of... 

In the initial attempt to scale up the reaction using ammonia in ethylene glycol at 180 °C to form lactam 7, the reaction, depicted in Scheme 3.6, did not go to completion, most likely due to the loss of ammonia during the longer time required to reach reaction temperature at this scale. On the gram scale, it was found that complete conversion could be achieved by heating at 140 °C in ethylene glycol and, on scale-up, improved performance was observed. 

Many organic reactions can be conducted very rapidly under microwave irradiation. Microwave-induced organic reaction enhancement chemistry techniques were used for the rapid formation of an ot-benzyloxy-p-lactam (10 in Fig. 4.2) and the hydrogenolysis of its benzyloxy group on a few-gram scale in 1-5 minutes with HC02NH4 and Pd/C in ethylene glycol as the reaction medium in a domestic microwave oven.243... 

Attempts to manufacture above the gram scale by several different routes have often resulted in violent decomposition during vacuum distillation. Distillation of more than a few grams demands caution. 

Recently, the 2-substituted L-glutamate analogue (2R)-a-(hydroxymethyl)gluta-mate (HMG) (2-151) has been reported by the group of Kozikowski to serve as a potential bioactive compound [73]. Since the synthesis of such a small molecule should be rapid and practical in order to produce it on a multi-gram scale, a domino... 

The octacyclic dimer (+)-94 could be obtained in short order from the tetracyclic bromide (+)-93 via a Co(I)-mediated reductive dimerization protocol first implemented in our prior syntheses of (+)-chimonanthine (7), (+)-folicanthine (8), and (—)-calycanthine (9) [7]. Simple exposure of intermediate (+)-93 to tris (triphenylphosphine)cobalt(I) chloride [48] in acetone under anaerobic conditions rapidly afforded dimer (+)-94 in 46 % yield. While higher yields (52 % yield) could be obtained in tetrahydrofuran on small scale, performing the reaction in acetone reproducibly afforded higher yields on gram scales. Notably, the product was obtained in similar efficiency on multi-gram scale (43 % yield on 8-g scale)... 

In a single step and on multi-gram scale, four C—H bonds were replaced by four C-O bonds in a highly stereoretentive manner with an efficiency approaching ca. 90 % yield per hydroxylation event. 

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