Reaction times

All reactions need some time to reach equilibrium, thus, reaction time is important for the CD yield and conversion rate. Commonly, the reaction time for -CD production is no more than 30 h in the industry. The reaction time of obtaining the maximum yield of a-, fi- and y-CDs is different even if the substrate and enzyme is the same. 

Many reports confirm notable reductions in reaction times when carrying out reactions under micro flow conditions. Concerning p-dipeptide synthesis, for example, a comparison between batch and micro-reactor processing was made for the reaction of Dmab-P-alanine and Fmoc-i-P-homophenylalanine [158]. While the micro reactor gave a 100% yield in 20 min, only about 5% was reached with the batch method. Even after 400 h, only 70% conversion was achieved. 

Most often, such enormous improvements are discussed in a classical way following conventional organic chemistry descriptions, e.g. providing the experimental protocol and briefly giving the results. This is usually not followed by a chemical-engineering explanation. Thus it remains unclear to what extent the batch 

AJthaugh various propiisals for the ni chani m of methanol homologation exist, the course of the reaction is still not fully understood. This is especially true for the activation of methanol with a concomitant C-0 bond scission. Also, the folc of the iodine promoter and of ligands remains unclear. This situation is controversial to the closely-related carbonylation of methanol to acetic acid with rhodium catalysts, where the oxidative addition of the intermediate methyl iodide to a rhodium (1) is a generally-accepted reaction path [SR]. 

First mechanistic considerations by Hecht and Kroper involved the formation of a methyl cobalt intermediate via esterification of methanol with the strong acid hydrocobait tetracarbonyl [5. Tiic mcihyi cobalt intermediate was ihou t to react with and CO to give acetaldehyde as the primary reaction product, which then was hydrogenated to ethanol (cf. Hquations (8) 10)). 

The formation of a methyl cobalt carbonyl species proceeds by way of a 

An acetyl cobalt intermediate 1 then formed by CO insertion (or methyl miration). which is subsequently hydrogenated to give ethanol and HCo(CO)4 (cf. Equations (13). (14)) (4]. 

Based on the wcU-known disproptntionation of Co2(CO)h in methanol yielding a CofCll OlOe cation (Equation (6)), Wender alternatively considered a nucleophilic attack of Co(C0)4 on coordinated methanol (cf. Equation (IS)) [4]. 

Flow reactors usually operate more nearly at constant pressure, thus at variable volume with gases. An apparent residence time is defined as the ratio of the reactor volume to the inlet volumetric rate, 

The true residence time is found by integration of the rate equation, 

Both the reaction rate, r, and the volumetric flow rate, V , must be known in terms of the number of mols, n, of the reference component. The apparent residence time is popularly used to indicate the loading of a reactor, 

A related concept is that of space velocity which is the ratio of a flow rate at STP (usually 60 F, 1 atm) to the size of the reactor. The most common versions in typical units are, 

GHSV (gas hourly space velocity) = (volumes of feed as gas at STP/hr)/(volume of the reactor or its content of catalyst) = SCFH gas feed/cuf t. 

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The vibrationally excited states of H2-OH have enough energy to decay either to H2 and OH or to cross the barrier to reaction. Time-dependent experiments have been carried out to monitor the non-reactive decay (to H2 + OH), which occurs on a timescale of microseconds for H2-OH but nanoseconds for D2-OH [52, 58]. Analogous experiments have also been carried out for complexes in which the H2 vibration is excited [59]. The reactive decay products have not yet been detected, but it is probably only a matter of time. Even if it proves impossible for H2-OH, there are plenty of other pre-reactive complexes that can be produced. There is little doubt that the spectroscopy of such species will be a rich source of infonnation on reactive potential energy surfaces in the fairly near future. 

Acetone in conjunction with benzene as a solvent is widely employed. With cyclohexanone as the hydrogen acceptor, coupled with toluene or xylene as solvent, the use of higher reaction temperatures is possible and consequently the reaction time is considerably reduced furthermore, the excess of cyclohexanone can be easily separated from the reaction product by steam distillation. At least 0 25 mol of alkoxide per mol of alcohol is used however, since an excess of alkoxide has no detrimental effect 1 to 3 mols of aluminium alkoxide is recommended, particularly as water, either present in the reagents or formed during secondary reactions, will remove an equivalent quantity of the reagent. In the oxidation of steroids 50-200 mols of acetone or 10-20 mols of cyclohexanone are generally employed. 

The condensation of aldehydes and ketones with succinic esters in the presence of sodium ethoxide is known as the Stobbe condensation. The reaction with sodium ethoxide is comparatively slow and a httlo reduction of the ketonic compound to the carbinol usually occurs a shorter reaction time and a better yield is generally obtained with the more powerful condensing agent potassium ieri.-butoxide or with sodium hydride. Thus benzophenone condenses with diethyl succinate in the presence of potassium [Pg.919]

Finally the influence of the temperature and addition of ethanol on the enantioselectivity of the Diels-Alder reaction was studied. Table 3.3 summarises the results for different aqueous media. Apparently, changes in temperature as well as the presence of varying amounts of ethanol have only a modest influence on the selectivity of the Cu(tryptophan)-catalysed Diels-Alder reaction in aqueous solution. However, reaction times tend to increase significantly at lower temperatures. Also increasing the alcohol content induces an increase of the reaction times. 

Table 3.4. Enantiomeric excess and reaction times of the copper(L-abrine)-catalysed Diels-Alder reaction of3.8cwith3.9in different solvents at 0 C.

Note that the reaction time in water is considerably shorter than that in organic solvents, despite the fact that the concentration of diene used for the reaction in water was less than one third of that for the reaction in the organic solvents. Contrary to the organic solvents, the reaction mixture in water is heterogeneous. It might well be that the low solubility of the Diels-Alder product (3.10c) in this solution reduces inhibition of the reaction by this compound. Consequently, product inlribition is likely to be more pronounced in the organic media. 

Due to the prolonged reaction times in organic solvents, cKmerisation of the diene occurs during the reaction, resulting in contaminated product mixtures after work-up. In contrast the reactions in water yield quantitatively the H-NMR-pure Diels-Alder adducts. 

Ingold and his co-workers used the competitive method in their experiments, in which nitration was brought about in acetic anhydride. Typically, the reaction solutions in these experiments contained o-8-I 4 mol of nitric acid, and the reaction time, depending on the reactivities of the compounds and the temperature, was 0-5-10 h. Results were obtained for the reactivities of toluene, > ethyl benzoate, the halogenobenzenes, ethyl phenyl acetate and benzyl chloride. Some of these and some later results are summarized in table 5.2. Results for the halogenobenzenes and nitrobiphenyls are discussed later ( 9.1.4, lo.i), and those for a series of benzylic compounds in 5,3.4. 

Using the microwave Just decreased the reaction time to 3-30minutes. The dudes in the article used a household, 500W Brazilian microwave (Yikesl). They cut a whole in the top of the microwave to allow the condenser apparatus to pass through the oven. They then killed themselves most likely. But not before they were able to scratch down this procedure as they slowly burned to death ... 

The above dream was scaled up in exact portions, as it was her first Her next dream had some variations to weights and measures, plus a longer reaction time... 

That looks great, Spiceboy. Thanks. Bra And to show you that Spiceboy isn t making this up, the following experimental will prove it. This was taken from the review [13] written by the same doctor that authored the progenitor PdCb article that Strike drew from to formulate this recipe, And just as Spiceboy says above, there is no need for any copper compound or balloon. Also, the reaction time is seriously shorter and the amount of PdCI2 catalyst needed is drastically reduced ... 

The authors say that the 5 day reaction time at room temp can be accelerated by raising the temperature of the reaction. But they did not specify how much heat or how much time would be reduced. 

METHOD 3 The authors next stepped back and considered the cosmic imbalance caused by that 6-day reaction time. The next recipe was what they came up with. 

Example 1 is repeated in exactly the same way, with the exception that in the isomerization step 250 mg of LiBr instead of 340 mg of Lil is used, and that the reaction time results to be of 10 hours,... 

The dilithiation can also be carried out with butyllithium in a 1 1 mixture of hexane and THF at -20°C (reaction time about 45 min). Subsequent alkylation is much faster than in diethyl ether. 

In the last case the reaction with bromochloromethane was much faster, and the reaction time (at 20-25°C) was 4 h. 

Note 1, Lengthening of the reaction time will lead to a decrease of the amount of starting compound, but more of the end product CH3CEC-Se-CjH5 will be present. 

Kote 1. The reaction time at room temperature was 2-3 h. At 40 C the isomerization was finished within 30 min. With a dilute (1 g per 10 ml) aqueous solution of K2C03.only about 5 min were required. 

Note 1. If the addition is carried out too slowly and/or the reaction mixture is allowed to stand for too long, part of the allenic anion may be converted into CcC-CHj-SPh, which gives HC C-CH2-SPh upon hydrolysis. If shorter reaction times are applied, the conversion of the CHjCEC-SPh appears to be incomplete. 

Note 1. This yield is lower than that reported in the literature. In our procedure no low-boiling light petroleum is used as co-solvent, so that the temperature of the boiling reaction mixture can become considerably higher, which may give rise to the formation of polymeric products and tars. Our reaction time is much shorter than that in the literature. The reaction with HCECCH2OH and HC=C-CH(CH3)0H failed. 

Note 1. Longer reaction times gave rise to lower yields and more polymer. 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

Then N-Boc-O-benzylserine is coupled to the free amino group with DCC. This concludes one cycle (N° -deprotection, neutralization, coupling) in solid-phase synthesis. All three steps can be driven to very high total yields (< 99.5%) since excesses of Boc-amino acids and DCC (about fourfold) in CHjClj can be used and since side-reactions which lead to soluble products do not lower the yield of condensation product. One side-reaction in DCC-promoted condensations leads to N-acylated ureas. These products will remain in solution and not reaa with the polymer-bound amine. At the end of the reaction time, the polymer is filtered off and washed. The times consumed for 99% completion of condensation vary from 5 min for small amino acids to several hours for a bulky amino acid, e.g. Boc-Ile, with other bulky amino acids on a resin. A new cycle can begin without any workup problems (R.B. Merrifield, 1969 B.W. Erickson, 1976 M. Bodanszky, 1976). 

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