Enhanced reaction control

In another glass (borosilicate) microreactor [channel dimensions = 350 pm (wide) x 52 pm (deep) x 2.5 cm (long)], Wiles et al. (2004b) prepared a series of 1,2-azoles, illustrating the synthesis of a pharmaceutically relevant core motif. Reactions were performed using electroosmo-tic flow (EOF) as the pumping mechanism and employed separate 

To synthesize these pharmaceutically interesting compounds, metha-nolic solutions of acetic acid 6 (2.0 eq.)/2-formylbenzoic acid 7 (1.0 eq.) and aniline 8 (2.0 eq.)/potassium cyanide 9 (1.2 eq.) were introduced into the reactor from separate inlets, thus ensuring the formation of HCN and the 

Using this approach, the authors found the optimal reaction conditions to be a reactant concentration of 0.2 M, dimethylformamide (DMF) as the reaction solvent, a reaction temperature of 22 °C, 10 mol% p-TsOH 12, and 5.0 eq. of the orthoester 13. Under the aforementioned conditions, the target material 11 was obtained in 43% yield, with a residence time of 

The conversion of carboxylic acids to esters is a fundamental transformation in the synthetic chemists toolbox, as such Wiles et al. (2003) investigated the ability to efficiently synthesize a series of methyl, ethyl, 

The ease of method transfer was subsequently demonstrated via substitution of acetyl chloride 19 with acetyl [D3]chloride 22, whereby operating the reactor under the aforementioned conditions, the authors obtained comparable results (98% conversion). This investigation provided important results for those in the area of isotope labeling as it demonstrated the ability to perform and optimize reactions using cheap, readily available precursors and then substitute labeled precursors to obtain the respective 

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Panke et al. (2003) also demonstrated enhanced reaction control, with respect to the temperature-sensitive synthesis of 2-methyl-4-nitro-5-propyl-2H-pyrazole-3-carboxylic acid 219, a key intermediate in the synthesis of the lifestyle drug Sildenafil (220) (Scheme 64). When performing the nitration of 2-methyl-5-propyl-2H-pyrazole-3-carboxylic acid 219 under adiabatic conditions, with a dilution of 6.01kg 1), Dale et al. (2000) observed a temperature rise of 42 °C (from 50 to 92 °C) upon addition of the nitrating solution. As Scheme 63 illustrates, this proved problematic as at 100 °C decomposition of the product 219 was observed and in order to reduce thermal decomposition of pyrazole 219, and increase process safety, the authors investigated addition of the nitrating solution in three aliquots, which resulted in a reduced reaction temperature of 71 °C and an increase in chemoselectivity unfortunately, the reaction time was increased from 8 to 10 h. 

Reduction of Chemoselective Reaction Time. Panke et al. demonstrated enhanced reaction control in the crucial step of nitration of the pharmaceutically relevant intermediate l-methyl-3-propyl-l//-pyrazole-5-carboxylic acid,... 

Reduction of Chemoselective Reaction Time Panke et al. demonstrated enhanced reaction control in the crucial step of nitration of the pharmaceutically relevant intermediate l-methyl-3-propyl-li/-pyrazole-5-carboxylic acid, a precursor to the lifestyle drug sildenafil citrate (Viagra) [5]. Control of the reaction temperature is absolutely necessary because the decay of the product above 100 C creates excess CO2 pressure and heat buildup. A standard 70 mL CYTOS microreactor was fed with reagents using external pumps. A flow rate of 1 mL/min was maintained within each channel, with the reaction temperature maintained at 90 °C. 

In an early example, Johnson and Johnson (New Brunswick, NJ) demonstrated the use of a CYTOS continuous flow reactor system for the synthesis of gram to kilogram quantities of drug substances for early clinical studies. In particular, the authors demonstrated the ability to perform a series of exothermic reactions, reporting on enhanced reaction control compared with standard batch techniques. One example was the synthesis of N-methoxycarbonyl-L-tert-leucine 44 (Scheme 6.25) via the addition of methyl chloroformate 45 to L-fcrf-leucine 46 in the presence of aqueous NaOH. Conducting the reaction in a flow reactor at 40°C resulted in the synthesis of N-methoxycarbonyl-L-rcrf-leucine 44 in 91.0% yield. 

In the synthesis of the tetracyclic intermediates for the synthesis of isoarborinol and its CDE-antipode femenol, the stereochemistry of the Diels-Alder reaction can be varied using various Lewis-acid catalysts in aqueous media (Eq. 12.36).97 Their results show that the hydrophobic effects play an important role in enhancing reaction rates and can control product distribution. Novel 2,4-dialkyl-1-alkylideneamino-3-(methoxycarbonylmethyl)azetidines were obtained from aldazines and... 

It may be desirable to operate in semibatch fashion in order to enhance reaction selectivity or to control the rate of energy release by reaction through manipulation of the rate of addition of one reactant. Other situations in which semibatch operation is employed include a variety of biological fermentations where various nutrients may be added at predetermined rates to achieve optimum production capacity and cases where one reactant is a gas of limited solubility that can be fed only as fast as it will dissolve. 

Dual Photo/Thermal Initiation Studies. A series of studies were performed using reactive formulations containing both a photoinitiator and a thermal initiator dissolved in the Derakane resin. The objective of these studies was to investigate a dual cure strategy in which the heat liberated by the photo-induced polymerization leads to the production of additional active centers by the dissociation of a thermal initiator. In this way, the dual cure strategy could offer both the temporal control of the start of the reaction afforded by the photopolymerization, as well as enhanced reaction rate and completeness of cure provided by the thermal initiation. 

The solvent process involves treating phthalonitrile with any one of a number of copper salts in the presence of a solvent at 120 to 220°C [10]. Copper(I)chloride is most important. The list of suitable solvents is headed by those with a boiling point above 180°C, such as trichlorobenzene, nitrobenzene, naphthalene, and kerosene. A metallic catalyst such as molybdenum oxide or ammonium molybdate may be added to enhance the yield, to shorten the reaction time, and to reduce the necessary temperature. Other suitable catalysts are carbonyl compounds of molybdenum, titanium, or iron. The process may be accelerated by adding ammonia, urea, or tertiary organic bases such as pyridine or quinoline. As a result of improved temperature maintenance and better reaction control, the solvent method affords yields of 95% and more, even on a commercial scale. There is a certain disadvantage to the fact that the solvent reaction requires considerably more time than dry methods. 

Anaerobic metabolism occnrs nnder conditions in which the diffusion rate is insufficient to meet the microbial demand, and alternative electron acceptors are needed. The type of anaerobic microbial reaction controls the redox potential (Eh), the denitrification process, reduction of Mu and SO , and the transformation of selenium and arsenate. Keeney (1983) emphasized that denitrification is the most significant anaerobic reaction occurring in the subsurface. Denitrification may be defined as the process in which N-oxides serve as terminal electron acceptors for respiratory electron transport (Firestone 1982), because nitrification and NOj" reduction to produce gaseous N-oxides. hi this case, a reduced electron-donating substrate enhances the formation of more N-oxides through numerous elechocarriers. Anaerobic conditions also lead to the transformation of organic toxic compounds (e.g., DDT) in many cases, these transformations are more rapid than under aerobic conditions. 

The intramolecular hetero-Diels-Alder reactions in functionalized 2(17/)-pyrazinones to give bicyclo adducts were found to undergo a significant rate enhancement using controlled microwave irradiation in ionic liquid doped solvents <2002JOC7904>. 

Unlike the case of enhancement of yield of product in a chemical reaction, control of qubit state transfers in a quantum computer is useful only if the control does generate sensibly perfect fidelity of population transfer. Fortunately, a typical qubit has a spectrum of states that is much simpler than that of a polyatomic molecule, so that control protocols that focus attention on the dynamics of population transfer in two- and three-level systems are likely to capture the essential dynamics of population transfer in a real qubit system. A large fraction of the theoretical effort devoted to describing such transfers has been confined to those simple cases. To a certain extent, many of these studies are analogous to... 

One of the reactions catalyzed by esterases and lipases is the reversible hydrolysis of esters (Figure 19.1, Reaction 2). These enzymes also catalyze transesterilications and the desymmetrization of mew-substrates (vide infra). Many esterases and lipases are commercially available, making them easy to use for screening desired biotransformations without the need for culture collections and/or fermentation capabilities.160 In addition, they have enhanced stability in organic solvents, require no co-factors, and have a broad substrate specificity, which make them some of the most ideal industrial biocatalysts. Alteration of reaction conditions with additives has enabled enhancement and control of enantioselectivity and reactivity with a wide variety of substrate structures.159161164... 

As in reactive distillation and reactive chromatography, many sorption-enhanced reaction processes are controlled by phase equilibrium in addition to reaction equilibrium. The situation is different for membrane reactors, where phase equilibrium between the phases adjacent to the membrane is often trivial and the process is... 

All of these control experiments are consistent with a mechanism in which the stilbenes 5 are in dynamic equilibrium with the equivalent benzylic alcohols 4 and the oxidative-cleavage reaction occurs on the latter. This equilibrium explains 1) the observed requirement for water for the stilbene oxidations 2) the unsymmetrical product distribution from both the alcohols and stilbenes and 3) the enhanced reaction rate of the chlorobenzyl alcohol 4b as compared to the stilbene analogue 5b at 120 °C. 

A suggestion was made that A add of the 2-hydroxy-2-propyl radicals of DAR to MA (Schemes 12.1 and 12.3) decreases with the viscosity increase,which would be a sign of a diffusion-controlled or a diffusion-enhanced reaction.In fact, an increase in viscosity 1200 times leads to a decrease in A add only 5 times and not by orders of magnitude, which does not allow the classification of the addition as almost a diffusion-controlled (diffusion-enhanced) reaction. 

The most smdied O-bonded transition metal enolates are titanium enolates . The reason for their success has beeu recognized in the fact that titanium enolates show an enhanced stereochemical control in C—C bond-forming reactions over simple lithium enolates and the possibility of incorporating chiral ligands at the titanium centre, a possibility which has lead to enantioselective aldol reactions with excellent enantiomeric excess. Moreover, titanium euolates have been used in oxidation reactions with remarkable diastereoselectivity. 

Catalyst-membrane systems are promising structured catalysts. The perspectives for control of heterogeneous catalytic reactions by the combination of a catalyst and a membrane selectively permeable for one of the reactants have been discussed [1]. Catalyst-membrane systems enhance reaction rate and selectivity due to the directed transfer of reactants and energy. 

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