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In Situ Monitoring of Chemical Reactions – A Molecular Video

ReactIR

Brian Wittkamp, Mettler-Toledo AutoChem, Inc.

How to do more with less is a consistent theme in today’s chemical development laboratories. Researchers are challenged with how quickly and cost-effectively they can deliver high quality chemical products and the processes used to make them. This in turn has driven a trend in industry to develop and adopt new methods of working, and new techniques to analyze chemical reactions.

The desire to gain reaction information is not a new one, and offline techniques such as HPLC have been used for many years for this purpose. HPLC provides unrivalled levels of access and sensitivity that enables researchers to gain quantitative information regarding reaction components at any time the reaction is sampled. However, the need to wait for samples to be analyzed results in delays in gaining the required information, which is significant when development speed is of the essence. Also, the inability to see what is happening in between samples, plus a lack of predictive qualities, can sometimes lead to a misunderstanding of reaction progress and mechanism. Because of this, there is a need for instantaneous reaction information to improve the efficiency of the optimization and scale-up of chemistry. In recent years, in situ reaction monitoring has grown in use for this purpose.

ReactIR™ is a real-time in situ reaction analysis system used to increase the understanding of chemical reactions. ReactIR™ monitors reactive chemistry using well understood mid-IR spectroscopy. A robust ATR probe is inserted directly into the vessel, spectra are taken and translated into a “molecular video” of the reaction. The concentration changes of all key reactive and transient species are monitored allowing for mechanism, pathway and kinetic determinations.

This white paper highlights examples where ReactIR™ was used to uncover key parameters in scientific investigations. It is not the intent to go into detailed findings, it is recommended to read the original publications for this purpose. Instead, the author highlights the context in which ReactIR™ helped researchers answer key questions.

Introduction

While the technique has gained increased popularity in recent times, the principal of in situ reaction monitoring dates back to 1961 when Farenfort1 introduced a new method of measurement that today is called Attenuated Total Reflectance (ATR). (For further reading on this topic a suggested reference is Internal Reflection and ATR Spectroscopy, Milan Milosevic, John Wiley and Sons, Jul 3, 2012, ISBN-10: 0470278323.)

The combination of mid infrared (MIR) spectroscopy, and the advantages ATR technology offers over transmission measurements, opened up new possibilities to monitor classical reactions in real time. These are used today by researchers and scientists to gain greater understanding of chemical reactions, and therefore improve the speed of and the science behind chemical development. Advantages include:

  • Being impervious to bubbles or solids due to the depth of penetration of incident radiation into the sample - ideal for hydrogenations and solid catalyst chemistries
  • Suitability for aqueous chemistry (12µm vs. several mm’s as with traditional transmission measurements) shorter pathlength means less sensitivity to water absorption bands
  • Being immersed directly into a reaction vessel - in situ, real time reaction measurements are now possible

In addition, this technique provides a number of advantages over offline techniques, such as:

  • Immediate access to real-time reaction information
  • No extractive sampling - measure chemistry in its natural environment, guaranteeing sample has not changed due to quenching or some other phenomena
  • Non-destructive - preserves chemistry integrity and reactant concentrations remain unchanged
  • Safety – reactions under high temperatures and pressures can be sampled without the need to take samples

In addition to these advantages, MIR spectroscopy adheres to the Beer-Lambert law where absorbance is proportional to concentration. This enables researchers to make either qualitative or quantitative measurements during the course of a reaction, depending on the exact information they are looking for.

One of the first uses of MIR ATR as an in situ reaction monitoring tool was a mechanistic study by Lynch et. al.2 where they investigated the manner in which a -lactam was formed in a low temperature reaction. To accomplish this, a custom glass reactor was used that contained a MIR ATR sensor mounted in the bottom of the reactor. During the reaction, a MIR spectrum was collected at regular intervals (e.g. one spectrum collected every minute) and it was determined by this in situ technique that the -lactam formed exclusively through a ketene intermediate. Without the ability to monitor this reaction in situ, there would not have been a way to make such a determination because of the compositional change that would have occurred when extracting a sample for offline analysis (the intermediate would probably have been destroyed).

Although a reactor with an “integrated” reaction monitoring device has its merits, it is not practical for general and widespread use. In 1995, Milosevic and Rein3 reported the first commercially available diamond-based MIR ATR probe. Now in a probe format this technology could be used in nearly all standard (and custom) laboratory and production vessels, making the technology applicable to more applications and uses.

In general, as its use became more widespread, many authors reported on a number of uses of MIR ATR spectroscopy. A general theme in these reported papers was the use of MIR ATR spectroscopy to determine:

  • Reaction initiation and endpoint
  • Mechanism and reaction pathway information
  • Reaction kinetics

Under a wide variety of conditions:

  • Super acids and bases
  • Toxic chemistry
  • Under high pressures and under vacuum
  • At high and low temperatures

Figure 1. Reaction concentration profiles versus time for the organic halide reactant (orange curve) and Grignard product (green curve). Dotted lines indicate the behavior seen when the reaction stalls due to presence of water.

The real time, in situ nature of this technology is not only extremely useful and key for gaining further insights into reaction behaviors, but critical in instances where safety can be maintained. Am Ende et. al.4 reported the use of in situ MIR ATR for the detection of a Grignard initiation and a condition where the reaction stalls due to water in the solvent, thus enabling the real time detection of a potential safety hazard in a highly exothermic reaction. Figure 1 shows the MIR trends for all the key reaction species and graphically shows their relative concentrations over the course of the reaction. It can be seen that the reaction initiates after 25 minutes and reaches its endpoint within two hours. The dotted lines illustrate how the reaction profile will look in the event of a stalled reaction. The ability to see this type of behavior in real time allows chemists to stop the addition of organic halide in the event of a stalled reaction, and prevent a potentially dangerous situation once re-initiation occurs.

Case Study 1: Catalytic Double Carbonylation of Epoxides to Succinic Anhydrides: Catalyst Discovery, Reaction Scope, and Mechanism

John M. Rowley , Emil B. Lobkovsky , and Geoffrey W. Coates*, Contribution from the Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301. J. Am. Chem. Soc., 2007, 129 (16), pp 4948–4960.

Bimetallic catalysts can be used to convert carbonylate -lactones to succinic anhydrides, which in turn are useful materials for biodegradable polyesters and synthetic intermediates. In this example, the double carbonylation of propylene oxide (PO) to methyl succinic anhydride (MSA) was studied to determine the reaction steps, kinetics and pathway via in situ MIR ATR reaction monitoring.

The current reaction sequence can be seen at the top of Figure 2. Advances in epoxide carbonylation have afforded a 2-step conversion sequence, however the researchers wished to reduce this to a single synthetic step to save time and eliminate the toxic lactones.

Figure 2a. Plot of the concentrations of BBL and MSA during double carbonylation of PO. Reaction performed in 1,4-dioxane and monitored by in situ IR spectroscopy (vC=O BB= 1827cm-1 and vC=O MSA = 1787cm-1). [PO]O = 1.0M, [1] = 4.0mM, PCO = 850psi, T = 40°C.

Figure 2b. Plot of the concentrations of BBL and MSA during double carbonylation of PO. Reaction performed in 1,4-dioxane and monitored by in situ IR spectroscopy (vC=O BB= 1827cm-1 and vC=O MSA = 1787cm-1). [PO]O = 1.0M, [1] = 4.0mM, PCO = 850psi, T = 40°C.

The double carbonylation of PO to MSA was carried out in a 100mL Parr pressure reactor with a MIR ATR probe mounted through the base of the reactor. The reaction conditions were 40°C and 850psi (58.6bar), with 1,4-dioxane as the solvent. A bimetallic catalyst consisting of aluminum/cobalt was used to perform this sequence in one double carbonylation step. In this instance, the use of MIR ATR spectroscopy enables the reaction to be monitored under actual conditions, eliminating the need to sample the reaction at the pressures it is performed under.

As shown in Figure 2, PO is linearly consumed to produce -butyrolactone (BBL). No MSA is observed until all the PO has been consumed, at which point BBL is consumed with a first order decay to produce MSA. The rate-determining step for each reaction was not overlapping, and therefore the mechanism and kinetics of each step could be studied independently.

Figures 3-5 show the in situ MIR ATR results of the investigation of the kinetics for each of the carbonylation steps. Various substrate concentrations, pressure (up to 69bar), catalyst loading and solvent type were investigated. The epoxide carbonylation was found to be zero order in epoxide and CO and first order in catalyst and solvent. The lactone carbonylation was found to be zero order in COO, first order in BBL and catalyst and inverse to solvent.

Figure 3. Inital rates of the formation of BBL and MSA as a function of the concentration of 1. Reactions performed in 1,4-dioxane and monitored with in situ IR spectroscopy (vC=O BBL = 1827cm-1 and vC=O MSA = 1787cm-1). [PO]O = 1.0M, PCO = 850psi, T = 40°C.

Figure 4. Plot of the formation of BBL as a function of time. Reactions performed in 1,4-dioxane and monitored with in situ IR spectroscopy (vC=O = 1827cm-1). [PO]O = 1.0M, [1] = 4.0mM, PCO = 850psi, T = 40°C.

Figure 5. Inital rates of the formation of BBL and MSA as a function of the concentration of 1. Reactions performed in 1,4-dioxane and monitored with in situ IR spectroscopy (vC=O BBL = 1827cm-1). [1] = 4.0mM, [BBL]O = 1.0M, PCO = 850psi, T = 40°C.

The researchers then sought to evaluate the proposed catalytic scheme for the double carbonylation. Since all of the species in the reaction come in contact with the ATR sensor, they all have the ability to absorb the MIR energy and thus generate a unique spectrum of each species. In this case, not only do the PO, BBL and MSA have unique MIR absorbance frequencies, but so do the various states of the catalyst species. The catalyst resting state of the epoxide carbonylation was determined to be a cobalt-acyl species (A in Scheme 2) by the appearance of the 1715cm-1 band. Once the entire PO has been converted to BBL, the 1715cm-1 peak disappears and is replaced by a peak at 1885cm-1, which is consistent with a free cobaltate species. Thus, it was proposed that the catalyst resting state is a cobaltate (B in Scheme 2) during the lactone carbonylation.

Case Study 2: Nitrosobenzene-Mediated C−C Bond Cleavage Reactions and Spectral Observation of an Oxazetidin-4-one Ring System

Joshua N. Payette and Hisashi Yamamoto, Department of Chemistry,
The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637

J. Am. Chem. Soc., 2008, 130 (37), pp 12276–12278


This case study focuses on a one-step oxidative C-C bond cleavage methodology utilizing nitrosobenzene as an oxidant. This bond cleavage methodology can be used by a broad range of ester and dicarbonyl substrates and is a measurable breakthrough over the more conventional multi-step and metal-mediated procedures. In this manner, chemists can produce a highly robust oxidative C-C bond cleavage for a diverse array of carbonyl compounds.

In order to verify that the cleavage is a single-step operation, observance of the spiro-oxazetidin-4-one species (structure 11 in Pathway 2) is a requirement. Failure of the spiro species to be present in the reaction medium would indicate a different pathway other than a single-step.

Figure 3a. 3-dimensional plot of FTIR spectra collected over time showing the consumption of the phenyl ester (7) reactant (1763, 1702cm-1) and the appearance of the N-phenyl imine (6) product (1695, 1679cm-1)

Figure 3b. 3-dimensional plot of FTIR spectra collected over time showing the consumption of the phenyl ester (7) reactant (1763, 1702cm-1) and the appearance of the N-phenyl imine (6) product (1695, 1679cm-1)

Figure 3 is the 3-Dimensional MIR spectral data collected with an in situ ATR probe at periodic intervals throughout the duration of the reaction. The reaction pathway can also be seen in Figure 3, which depicts conversion of the phenyl ester (structure 7) to the corresponding N-phenyl imine (structure 6). Less than one minute following the addition of nitrosobenzene to the lithium enolate, a band at 1846cm-1 begins to appear and grows in intensity (concentration) before reducing completely to zero  nearly two hours after reaction initiation. Investigation into the MIR spectral data of cyclic compounds led to a correlation that the 1846cm-1 band is characteristic of a four-membered spiro ring compound. Therefore, assignment of this band was made to the spiro-oxazetidin-4-one intermediate (structure 14). This is the first reported direct evidence of this reactive intermediate.

Extractive sampling methods for offline analysis would have failed to preserve the intermediate and therefore been unsuccessful in detecting and confirming its existence. Due to the observance of this intermediate in the MIR data, there is confirmation that the conversion is a single-step pathway. Once the reaction is allowed to warm to -20°C from the initial reaction temp of -78°C, the concentration of the intermediate decreases as it converts to the N-phenyl imine product that has a doublet at 1695/1679cm-1 (seen in Figure 3 with the doublet increasing in intensity until steady state - end of the reaction - is reached).

Figure 4 is a plot of MIR absorbance vs. time for the three species of interest in this reaction - lithium enolate of the phenyl ester, oxazetidin-4-one intermediate and N-phenyl imine product as highlighted in the reaction in Figure 4.

Figure 4a. Reaction concentration profiles versus time of the enolate reactant (7), reactive intermediate (14) and N-phenylimie product (6)

Figure 4b. Reaction concentration profiles versus time of the enolate reactant (7), reactive intermediate (14) and N-phenylimie product (6)

It can be seen in the plot in Figure 4 that immediately following addition of the nitrosobenzene to the lithium enolate (Lithium enolate 7 curve), the reactive intermediate (spiro-oxazetidin-4-one) forms (Intermediate 14 curve). Relatively gradual conversion of the intermediate to the N-phenyl imine product can be seen in the graph as the temperature of the reaction is increased to -20°C. At -20°C, the conversion increases dramatically until the intermediate is completely consumed and the reaction endpoint is reached. It should be noted that the product profile (N-phenyl imine 6 curve) is lower in intensity due to it being a measurement of only one isomer of the product.

Case Study 3: Conversion of Bis(trichloromethyl) Carbonate to Phosgene and Reactivity of Triphosgene, Diphosgene, and Phosgene with Methanol1

Lucia Pasquato ,*† Giorgio Modena ,† Livius Cotarca ,*‡§ Pietro Delogu ,‡ and Silvia Mantovani ‡

Centro CNR Meccanismi di Reazioni Organiche† and Dipartimento di Chimica Organica Università di Padova, via Marzolo 1, 35131 Padova, Italy, and Industrie Chimiche Caffaro SpA,‡ Centro Ricerche Torviscosa, P-le F. Marinotti 1, 33050 Torviscosa Udine, Italy

J. Org. Chem., 2000, 65 (24), pp 8224–8228

There is a growing interest in the use of triphosgene (bis(trichloromethyl) carbonate or BTC) in organic synthesis. The primary drivers are the use of triphosgene as a solid is safer and easier to handle (and transport) than compared to phosgene, as well as a number of derivatives can be made such as unsymmetrical ureas, isocyanates, carbamoyl chlorides, etc. A key component needing to be understood with this type of chemistry is the safety aspect of triphosgene - under what conditions can triphosgene release phosgene in a safe and controlled manner. A second phase of this study was the mechanism investigation of triphosgene toward nucleophiles in the presence and absence of catalysts and what is the likelihood of producing harmless quantities of phosgene during these reactions.

Pasquato et. al. were interested in investigating the depolymerization of triphosgene (1) in the presence of chloride ions. To monitor the depolymerization they used in situ MIR ATR technology to monitor the progress and order in which the depolymerization of triphosgene takes place in real time without having to extract a sample of this toxic material for offline analysis. MIR ATR showed that triphosgene (1) went through an intermediate (2) diphosgene, which allowed the mechanism of the process to be understood. Secondarily, they investigated the reaction of triphosgene (1) with methanol (weak nucleophile) in the presence and absence of chloride ions. Later they went on to further study this same reaction with disphosgene (2) and phosgene (3) with proton NMR, but for the purpose of this white paper we will only focus on the MIR ATR investigations of triphosgene. Further details of the NMR portion of this study are covered in the complete paper.

Several experiments were carried out examining the decomposition of triphosgene (1) to phosgene (3) using chloride ions in different solvents or undiluted salts (5-10% w/w) in order to determine the products of the reaction and the stoichiometry. A typical experiment involved a solution of triphosgene in n-hexane (10% w/w) treated with Aliquat 336 (3 mol % vs triphosgene) added at one time. The reaction was carried out at room temperature and was monitored via real time, continuous in situ MIR ATR technology.

Figure 5. Absorbance vs Time(s) as monitored by ReactIR™ in the Aliquat (3%) catalyzed conversion of tripohisgene (11% w/w) to phosgene carried out in n-hexane at room temperature

The MIR data collected identified three distinct species: the reagent, triphosgene (1); the product, phosgene (3); and an intermediate. Detailed analysis of the MIR data undoubtedly identified unique bands characteristic to diphosgene (2) as being the intermediate. The MIR profiles (reaction species concentration versus time) collected in this study are reported in Figure 5. The MIR band assignments for each of the three reaction species are 1177 cm-1 for triphosgene, 836 cm-1 for phosgene and 1054 cm-1 for diphosgene. The characteristic shape of the diphosgene profile in Figure 5 is indicative of an intermediate where the concentration increases in the early stages of the reaction and then decreases as it is being converted to the desired phosgene product. The phosgene produced during this reaction was then condensed in a methanol solution at -12°C. Quantitative analysis of the solution at the end of the reaction indicated there to be three equivalents of dimethyl carbonate formed per mole of triphosgene.

This experimental evidence points to the mechanism outlined in Scheme 7, which is centered on the nucleophilic role of the chloride ion. The chloride ion is a strong nucleophile in this instance that attacks the carbonyl carbon of triphosgene producing both diphosgene and phosgene. Subsequently, the diphosgene reacts with a chloride ion to produce two moles of phosgene. Chloride ion is needed in catalytic amounts since it is not consumed in the process.

These results indicate that the decomposition of the triphosgene produces safe quantities of phosgene in situ when using a catalytic amount of chloride ions (3-5%). The authors cite their confirmation that triphosgene is a solid equivalent.

Case Study 4: Investigation of an Efficient Palladium-Catalyzed C(sp)−C(sp) Cross-Coupling Reaction Using Phosphine−Olefin Ligand

Wei Shi †, Yingdong Luo †, Xiancai Luo †, Lei Chao †, Heng Zhang †, Jian Wang ‡ and Aiwen Lei *†

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, P. R. China, and Mettler-Toledo AutoChem Inc., 7075 Samuel Morse Drive, Columbia, Maryland 21046

J. Am. Chem. Soc., 2008, 130 (44), pp 14713–14720

This example deals with a Pd catalyzed cross-coupling between a haloalkene (1) and a terminal alkyne (2) to form a diyne (3) as can be seen in Scheme 8. This is a very efficient means to synthesize 1,3-diynes, which play an important role as building blocks in new materials such as conjugated oligomers and polymers, liquid crystals, non-linear materials, molecular wires, etc.5 The goal of this study was to implement in situ MIR ATR for real time monitoring and measurements of reaction rate under various conditions, get enough data points to minimize the number of required experiments, while gaining measurable insight into the reaction mechanism. There are other papers from the same author6,7 describing a similar mechanistic approach.

Real time monitoring of cross-coupling reaction with in situ MIR ATR clearly shows a distinct measurement band for both the bromoalkyne (1) at 973cm-1 and the product (3) at 955cm-1 in Figure 6a. The 3D waterfall plot (MIR spectra collected at a defined interval during the reaction period) in Figure 6b shows that these unique MIR bands for the two species can be trended over time to show the concentration change as the bromoalkyne (1) is consumed and the product (3) is produced. This gives a good picture of how the reaction progresses.

Figure 6a. Shows the unique FTIR absorbance for bromoalkyne 1 and product 3.

Figure 6b. 3-dimensional plot of FTIR spectra collected over time showing the decrease in starting material1 (973 cm-1)

Figure 6c. increase in the product 3a (955cm-1)

An interesting use of the collected MIR spectral data is to process it through a kinetics analysis method developed by Blackmond8. In this study, the authors investigate two well defined sets of reaction conditions, Reaction A and B, whereby Reaction B differs from A by the ratio of the reactants concentration versus catalyst concentration. It can be seen in Figure 7 that the initial rate for the two sets of reaction conditions is the same, meaning there is no catalyst deactivation or poisoning. Had there of been poisoning or deactivation, Reaction A (which has relatively less catalyst than Reaction B) would show a slower reaction rate.

Figure 7. Graphical representation of reaction rate vs. concentration demonstrating that the plateau effect indicates no catalyst deactivation or poisoning

Figure 8. Straight line fit of the varying bromoalkyne 1 and direct overlay of the three reactions indicate zero-order in both reactants, 1c and 2g

The third set of experiments was conducted by varying the concentration of bromoalkyne (1), with everything else remaining unchanged. As Figure 8 shows, this did not affect the initial reaction rate. This observation, together with the previous experimental results, indicates that the reaction is zero-order in both reactants.

Combining the MIR spectral data with Reaction Progress Kinetics Analysis (RPKA) developed by Prof. Blackmond in a package called iC Kinetics™, researchers and scientists are able to deduce the power law rate equation for this reaction, Figure 9. In addition, the iC Kinetics™ module allows for simulation runs to determine the optimum reaction conditions to reach 90% conversion. All of this achieved through a minimum of three reaction progress experiments, which by other methods would have resulted in numerous additional experiments and larger quantities of potentially expensive reaction materials.

Conclusions

As stated previously, it was not the intent within this white paper to go into details regarding the scientific findings of the authors. Instead, it is hoped that it has been demonstrated that ReactIR™ in situ spectroscopy, when used either on its own or in conjunction with other techniques, is capable of providing important clues that lead researchers to understanding the kinetics, pathway and mechanisms of chemical reactions.

Specifically, the examples demonstrate:

  • ReactIR™ in situ spectroscopy has been shown to provide valuable, complementary information that enables researchers determine the mechanism and pathway of a number of different types of chemical reactions
  • Information collected using ReactIR™ in situ spectroscopy is of a highly complementary nature to other structural data such as NMR
  • ReactIR™ in situ spectroscopy can be used to study reactions under a wide range of conditions such as high and low temperatures, high pressures, and can deal with conditions such as gas formation and evolution and catalyst particles being present

It should be noted that although all the examples cited in this white paper were carried out in a batch reactor (lab and plant), continuous flow reactors have recently gained greater use in the chemical development process. In situ MIR ATR technology can also accommodate the analysis needs of continuous reactor systems as well9,10.

References

  1. J. Farenfort, Spectrochim. Acta 1961, 17, 698-701.
  2. J.E. Lynch et. al., J. Org. Chem. 1989, 54, (16), 3792-3796.
  3. M. Milosevic, D. Sting, A. Rein, Spectroscopy 1995, 10, 44-49.
  4. Preparation of Grignard Reagents: FTIR and Calorimettic Investigation for Safe Scale-Up, David Em Ende, Pamela J. Clifford, David M. DeAntonis, Charles SantaMaria, and Steven J. Brenek, Org. Proc. Res. Dev., 1999, 3 (5), pp 319-329.
  5. H. Stefani et. al., 13th Brazilian Meeting on Organic Synthesis 31-Aug thru 4-Sep 2009, Synthesis of symmetrical 1,3-diynes via homocoupling reaction of n-butyl alkynltellurides.
  6. Lei et. al., Org. Lett. 2008, 10, (13), 2661-2664.
  7. Lei et. al., Chemistry: A European Journal, 2009, 15, 3823-3829.
  8. D.G. Blackmond, Angew. Chem. Int. Ed 2005, 44, 4302-4320.
  9. Carter, H. Lange, S. Ley et. al., Org. Proc. Res. & Dev. 2010, 14, 393-404.
  10. K. Jensen, J. Keybl, Ind. Eng. Chem. Res. 2011, 50, 11013-11022.

Additional Resources

  • Webinar: Reaction Progress Kinetic Analysis http://us.mt.com/us/en/home/events/webinar/ondemand/kinetic.html
  • Webinar: Recent Advances in Organic Chemistry Webinar Series http://us.mt.com/us/en/home/events/webinar/ondemand/organic-chem.html
  • Video: ReactIR Method of Measurement www.mt.com/ReactIR
  • “FTIR Study Measuring the Monomer Reactivity Ratios for Ethylene Vinyl Acetate Polymerization in Supercritical CO” Ind. Eng. Chem. Res., 2009, 48 (3), 1384-1390
  • “Quantification of hydrolysis of toxic organophosphates and organophosphonates by diisopropyl fluorophosphatase from Loligo vulgaris by in situ Fourier transform infrared spectroscopy” Jürgen Gäb a,b, Marco Melzer a,c, Kai Kehe d, André Richardt e, Marc-Michael Blum a,* Analytical Biochemistry; 385 (2009), 187–193
  • “Reactions of Synthetic [2Fe-2S] and [4Fe-4S] Clusters with Nitric Oxide and Nitrosothiols” Todd C. Harrop, Zachary J. Tonzetich, Erwin Reisner, and Stephen J. Lippard* J. Am. Chem. Soc.,; (Article); 2008, 130 (46), pp 15602–15610
  • “Investigation of an Efficient Palladium-Catalyzed C(sp)-C(sp) Cross-Coupling Reaction Using Phosphine-Olefin Ligand: Application and Mechanistic Aspects” Wei Shi, Yingdong Luo, Xiancai Luo, Lei Chao, Heng Zhang, Jian Wang, and Aiwen Lei, J. Am. Chem. Soc.; (Article); 2008, 130 (44), pp 14713–14720
  • “Anionic Snieckus-Fries Rearrangement: Solvent Effects and Role of Mixed Aggregates” Jason C. Riggs, Kanwal J. Singh, Ma Yun, and David B. Collum* J. Am. Chem. Soc.; (Article); 2008, 130(41), 13709–13717
  • “Nitrosobenzene-Mediated C-C Bond Cleavage Reactions and Spectral Observation of an Oxazetidin-4-one Ring System” Joshua N. Payette and Hisashi Yamamoto* J. Am. Chem. Soc.; (Communication); 2008, 130 (37), 12276–12278
  • “Mechanistic Studies of the Copolymerization Reaction of Oxetane and Carbon Dioxide to Provide Aliphatic Polycarbonates Catalyzed by (Salen)CrX Complexes” Donald J. Darensbourg,* Adriana I. Moncada, Wonsook Choi, and Joseph H. Reibenspies J. Am. Chem. Soc.; (Article); 2008; 130(20); 6523-6533
  • “On the Nature of Rate Acceleration in the Synthesis and Fragmentation of Triazolines by Brønsted Acid: Secondary Catalysis by Water (Hydronium Triflate)” Ki Bum Hong, Matthew G. Donahue, and Jeffrey N. Johnston* J. Am. Chem. Soc.; (Article); 2008, 130(7), 2323-2328
  • “Spectroscopic Determination of Hydrogenation Rates and Intermediates during Carbonyl Hydrogenation Catalyzed by Shvo’s Hydroxycyclopentadienyl Diruthenium Hydride Agrees with Kinetic Modeling Based on Independently Measured Rates of Elementary Reactions” Casey, C. P.; Beetner, S. E.; Johnson, J. B. J. Am. Chem. Soc.; (Article); 2008; 130(7); 2285-2295

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