Reaction conversion, monitoring

Striking support of this contention is found in recent data of Castro (16) shown in Figure 14. In this experiment, the polymerization (60-156) has been carried out in a cone-and-plate viscometer (Rheometrics Mechanical Spectrometer) and viscosity of the reaction medium monitored continuously as a function of reaction time. As can be seen, the viscosity appears to become infinite at a reaction time corresponding to about 60% conversion. This suggests network formation, but the chemistry precludes non-linear polymerization. Also observed in the same conversion range is very striking transition of the reaction medium from clear to opaque. 

Analytical Methods. A Schimadzu Liquid Chromatograph was used to monitor the reaction conversion and to assign chemical and chiral purity to the final product. Structures were verified by HNMR spectra obtained on a Bruker (Model UltraShield 400 spectrometer). Optical rotations were measured on a Perkin Elmer Model 341 Polarimeter. 

The deprotection of carbobenzyloxy protected phenylalanine was carried out in a low-pressure test unit (V= 200 ml) equipped with a stirrer, hydrogen inlet and gas outlet. The gas outlet was attached to a Non Dispersive InfraRed (NDIR) detector to measure the carbon dioxide. During the reaction the temperature was kept at 25 °C at a constant agitation speed of 2000 rpm. In a typical reaction run, 10 mmol of Cbz protected phenylalanine and 200 mg of 5%Pd/C catalyst were stirred in a mixture of 70 ml ethanol/water (1 1). The Cbz protected phenylalanine is not water-soluble but is quite soluble in alcoholic solvents conversely, the water-soluble deprotected phenylalanine is not very soluble in alcoholic solvents. Thus, the two solvent mixture was used in order to keep the entire reaction in the solution phase. Twenty p.1 of the corresponding modifier was added to the reaction mixture, and hydrogen feed was started. The hydrogen flow into the reactor was kept constant at 500 ml/minute and the progress of the reaction was monitored by the infrared detection of C02 in the off-gas. 

The reaction was monitored by H-NMR. When complete conversion was obtained, the solvent was removed and the crude reaction was filtered through a short silica gel column using t-butyl methyl ether as eluent. The resulting solution was concentrated using a rotatory evaporator to give N-acetylphenylalanine methyl ester in quantitative yield as a white solid. 

Progress of the reaction was monitored using a GC equipped with a FID on an achiral CP 1301 capillary column (30 m x 0.25 mm x 0.25 m film) and N2 as carrier gas. Enantiomeric purity of 2-octanol was analysed after derivatization with acetic anhydride (see below) using a CP-Chirasil Dex-CB column (25 m x 0.32 mm x 0.25 pm film, column B) and H2 as carrier gas. Enantioselectivities (expressed as the enantiomeric ratio E) were calculated from enantiomeric excess of the product and conversion as previously reported. Retention times and methods are listed in Table 3.1. 

The reaction was started with the addition of 350 kU hydroxynitrile lyase from M. esculenta. The reaction mixture was vigorously stirred and the reaction was monitored by gas chromatography (GC) until the equilibrium conversion of 22 % was reached ( 1.5 h). 

Last but not least, DSC is a powerful technique for many other polymer-relevant aspects such as monitoring of curing reactions, detection of degradation, determination of heat capacity of chemical conversions, monitoring of initiator decomposition, etc. 

A solution of (+ )-car-2-ene (4.08 g, 30 mmol) in petroleum ether (bp 40-60 X, 500 mL) containing toluene (3.1 mL) was irradiated with a 450-W Hanovia medium-pressure Hg lamp using a Vycor filter. The reaction was monitored by GC and the irradiation continued until 93 % conversion (50 h) had occurred. The solvent was slowly distilled off using a Vigreux fractionating column and the residue was distilled at 130-140 C. The product was purified by preparative GC yield 3.04 g (60%). 

To Fmoc 0-glycosyl threonine (erf-butyl ester 20 (290 mg, 0.4 mmol) dissolved in dry dichloromethane (5 mL) is added dry trifluoroacetic acid (3 mL) at 0°C. The mixture is allowed to warm to room temperature, and the reaction is monitored by TLC (dichloro-methane-ethanol 10 1). After 3 h, the conversion is complete. The solvent is evaporated in vacuo. Toluene (10 mL) is codistilled in vacuo from the remainder. Small amounts of an unpolar impurity are separated by flash chromatography on silica gel (20 g) in dichloro-methane-ethanol (15 1) yield 230 mg (90%) [a]D 69.7° (c 1, CHC13) Rf 0.32 (CH -ethanol 10 1). 

VI, obtained from stereospecific reactions of the corresponding optically active alcohol (11) with thionyl chloride, phosphorus pentachloride, etc., was not racemized under any of the reaction conditions. Monitoring the carbonyl absorption frequencies in the IR during these decarbonylations showed that the transformations II — III — IV took place during the conversion of V to racemic VI. Thus rearrangement or decomposition or both could be responsible for the racemization. 

In the second manifold, the O2 is quantitatively converted to CO2 by combustion. The reaction occurs over several minutes by recirculation of the gas over Pt/graphite at 900°C. The C02 produced is condensed into a cold finger as it is formed the reaction is monitored through the pressure changes. Once the conversion is complete, the CO2 is transferred to second cold finger and its pressure determined using a capacitance manometer or strain gauge. The quantity of CO2 is directly related to the quantity of O2 present in the reaction solution and the isotope content is... 

A solution of 10 g of the (S.y-unsauiratcd bicyclic ketone 55 (cf. Sch. 30) in lOOOmL of acetone was purged with argon and irradiated in a water-cooled quartz vessel placed in a Rayonet RPR-208 photochemical reactor equipped with RUL-3000 lamps (/. 300 nm). Irradiation was continued for 72 h and the reaction was monitored by tic. After 72 h of irradiation, the conversion was 98% and the only detectable compound was the ODPM rearrangement product, tricyclo[3.3.0.0.0]octane-3-one 57. The solvent was distilled off and the residue was chromatographed over silica gel using a benzene/ ether solvent mixture. The product which was eluted (8.6 g) was further distilled under vacuum (50 °C/1 mm) to get the pure ODPM rearrangement product (tricyclic ketone 57) in 81% yield with 99.5% purity. The quantum efficiency determined was found to be 4> = 1.0. 

The development of a normal-phase HPLC method was warranted due to the presence of phthalic anhydride, which is unstable in water. Analysis in organo-aqueous solvent systems that are used in RPLC would lead to an on-column reaction forming the respective carboxylic acid degradation product. Figure 5-5 shows the chromatogram obtained for the separation of 9,10-anthraquinone from the reactants and impurities on a silica column. The method was successfully applied to monitor the reaction conversion and also to determine the stability of 9,10-anthraquinone at the specified storage conditions. 

In Section 8.2, the aim of analysis is emphasized especially for the API (active pharmaceutical ingredient) and the drug product. The workflows and the rationale at major decision points during synthetic processing steps where HPLC can be applied in process development are elaborated upon. For example, a fast method is needed to monitor reaction conversion of two components. However, a more complex method would be needed for stability-indicating purposes where multiple degradation products, synthetic by-products, and excipient peaks need to be resolved from the active pharmaceutical ingredient. 

Reaction Conversion. Methods that monitor reaction conversion should ensure the resolution of all solvents and in-process impurities from the reactants and the desired intermediate. The goal here is to monitor product A going to product B—in essence, measuring the disappearance of A or completion of the reaction if reagent A is used in excess. Also, the concentration of product B may be needed as well as the purity of product B to control any undesired by-products. 

NHj was bubbled into a mixture of a 2//-3,l-benzoxazinc-2,4(l//)-dione 13 (O.O.S mol) in DMF (50 mL) at rt. The reaction was monitored by IR spectroscopy of aliquots and. when complete conversion was indicated (15-30 min), the mixture was degassed with to remove (NH ljCOj. POCI3 (8.5 mL) was then added dropwise at 0-15 " C. The resulting mixture was heated for 30 min at 40- 60 C, then cooled to rt, and H O (15 20 mL) was added. A primary amine or NH3 was then added until the mixture was basic, and the resulting solution was heated at 100 until TLC indicated conversion to the desired product. On cooling, the product crystallized and was isolated by filtration. In some cases, addition of HjO was necessary to cause crystallization. 

The first step determines the functionality degree and can be tuned according to the needs of the target (trans)esterification reaction. The succession of the reaction conversions, as well as the assessment of the completeness of the reactions can be conveniently monitored by hr-MAS as illustrated... 

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