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Yearly Archives: 2011

Nanoparticle Salad: A general route to Metal Oxide Nanoparticles using Green Chemistry

“Green Nanochemistry: Metal Oxide Nanoparticles and Porous Thin Films from Bare Metal Powders” Engelbert Redel, Srebri Petrov, Ömer Dag , Jonathon Moir, Chen Huai, Peter Mirtchev, and Geoffrey A. Ozin, Small2011DOI: 10.1002/smll.201101596

Advocates for green chemistry and nanotechnology have both promised technological solutions to society’s great challenges. Some of the barriers to widespread adoption of nanotechnology have been outlined by Jim Hutchison, and many of these barriers can be addressed by green chemistry. In particular the two issues that the current paper addresses are the excessive waste and the potential hazards associated with the metal precursors.

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Inherently Flame-Retarding Polymers

“Preparation of flame-retarding poly(propylene carbonate)” Cyriac, A.; Lee, S. H; Varghese, J. K.; Park, J. H.; Jeon, J. Y.; Kim, S. J.; Lee, B. Y. Green Chem. 2011, 13, 3469-3475. DOI: 10.1039/C1GC15722A

During graduate school in California I was very aware of the tremendous amount of household furniture loaded with flame retardant polybrominated diphenyl ether chemicals. Those chemicals do a great job of reducing the flammability of numerous petroleum-based products. Unfortunately their non-covalent incorporation in the polymers speeds their environmental release.  Once in the environment, they break down slowly and bioaccumulate. Additionally there are numerous human health and ecological concerns with these chemicals, including their association with decreased fertility in humans (ref). That is why this paper on flame-retarding poly(propylene carbonate) (PPC) caught my eye. Another reason could have been the flames in their graphical abstract!

TDI = toluene 2,4-diisocyanate; TPU = thermoplastic polyurethane

As luck would have it the chemistry is neat too, flames aside. The researchers begin by highlighting (bragging about?) the fact that they have an actual pilot plant in which they use their cobalt-salen-based catalyst to polymerize CO2 and propylene oxide to PPC (Note: experiments from this study were not performed in the pilot plant). The catalyst displays high turnover frequency (15,000/h) and produces high molecular weight polymers (Mn = 300,000).

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Metal-free, Organocatalytic Intramolecular C-H Amination

“Organocatalytic, Oxidative, Intramolecular C-H Bond Amination and Metal-free Cross-Amination of Unactivated Arenes at Ambient Temperature” Antonchick, A. P.; Samanta, R.; Kulikov, K.; Lategahn, J. Angew. Chem. Int. Ed. 2011, 50, 8605-8608. DOI: 10.1002/anie.201102984

For constructing aryl C-N bonds, the traditional synthetic sequence (i.e., what we teach undergrads) involves nitration followed by reduction, the nitration requiring harsh conditions and the reduction generating a stoichiometric amount of Sn waste.

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More recently, Buchwald and Hartwig have improved on this through the use of catalytic Pd. This reaction, however, requires a pre-oxidized aryl halide, which must be prepared prior to coupling.

C-H bond amination has been highlighted recently as a method to streamline the synthesis of aryl C-N bonds (see the work of White or Dubois for examples of allylic and aliphatic C-H amination reactions, respectively). Fewer synthetic steps means less waste and an overall greener reaction. Most catalytic C-H aminations, however, require the use of Rh, an expensive heavy metal. The Antonchick group recently reported the metal-free, organocatalytic synthesis of carbazoles by aryl C-H amination. This chemistry is novel and complements the work others are doing to use earth-abundant metal complexes as C-H amination catalysts (esp. Fe and Cu).

The Antonchick group starts by optimizing the conditions for the synthesis of N-protected carbazole 2a from the precursor 2-aminobiphenyl 1a in 81 % isolated yield from a 12 hr reaction in hexafluoro-2-propanol (HFIP) at room temperature.

They then improve their conditions by using catalytic amounts of iodoarene in the presence of peracetic acid as their oxidant avoiding the generation of a stoichiometric amount of iodobenzene waste from their initial conditions. Note that their optimized conditions require a mixed solvent system consisting of HFIP and methylene chloride.

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More Stahl Aerobics

“Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective Aerobic Oxidation of Primary Alcohols” Hoover, J. M.,; Stahl, S. S.  J. Am. Chem. Soc. 2011. ASAP. DOI: 10.1021/ja206230h

To quickly follow up yesterday’s post on aerobic alcohol oxidation, I thought that this new paper from the Stahl lab on the same topic was worth mentioning.  While their continuous flow process for alcohol oxidation was a pretty big improvement over many existing methods, the reagents necessary were not ideal.  Toluene and pyridine are both toxic, and palladium is not extremely abundant, especially compared to 1st row transition metals.  So there was plenty of room for improvement, which is why I was really psyched to see this new catalyst system for primary alcohol oxidation that was published a few days ago. Virtually all of the reaction components have been replaced by greener reagents:  acetonitrile instead of toluene, N-methylimidazole instead of pyridine, and catalytic TEMPO/(bpy)Cu(I) instead of palladium acetate.  Unlike most aerobic alcohol oxidations, an atmosphere of pure oxygen was not necessary – the oxygen present in ambient air was enough for the reaction to run efficiently.  And the reaction is run at room temperature to boot.  It’s hard to imagine that this reaction would be more difficult to scale up using their flow reactor than the Pd-catalyzed version, although you never know I suppose.

There’s loads more in the paper on their catalyst development studies, and on the chemoselectivity of this process for primary alcohols versus secondary ones – definitely worth reading!

The Problem with Oxygen

“Development of safe and scalable continuous-flow methods for palladium-catalyzed aerobic oxidation reactions” Ye, X.; Johnson, M. D.; Diao, T.; Yates, M. S.; Stahl, S. SGreen Chemistry, 2010, 12, 1180-1186.  DOI: 10.1039/c0gc00106f

We’ve had a pair of posts recently about using oxygen as an terminal oxidant in cross-coupling and biomass degradation, and as a green oxidant, it’s pretty hard to beat.  So I was a little surprised to learn that of the many cool aerobic synthetic methods that have been developed in the last decade, very few are used in industry.  The big drawback, especially on large scale, is safety – oxygen is usually the limiting reagent in the combustion reaction, and things can get pretty crazy when you have an oxygen-enriched atmosphere (and much crazier with liquid oxygen – check out this awesome video, and this one that Marty had in his last post).  So while stirring 100 mL of toluene under a balloon of pure oxygen might be fine, doing the same thing with 100 L is problematic.

This setup doesn't scale up very well

Safety aside, these reactions suffer because proper gas-liquid mixing is more difficult to achieve as you scale up.  All of this prompted a collaboration between Eli Lilly and Shannon Stahl‘s lab to develop a scalable continuous-flow method for aerobic alcohol oxidation, which avoids these problems. (more…)

Oxygen, Nature’s Oxidant for Nature’s Feedstocks.

“Selective catalytic conversion of biobased carbohydrates to formic acid using molecular oxygen”R. Wolfel, N. Taccardi,  A. Bosmann, P. Wasserscheid, Green Chemistry, 2011, DOI: 10.1039/c1gc15434f

Graphical abstract: Selective catalytic conversion of biobased carbohydrates to formic acid using molecular oxygen

All of us have a very personal relationship to the oxidizing power of oxygen. We use oxygen to turn our food into energy, CO2 and water. There are a number of enzymes and pathways that aid this process, each aiding the reaction of food and oxygen toward the creation of CO2 and water.  Now the key to turning complex biomass into usable small molecules is the ability to control this reaction so that we can extract usable chemical building blocks without ending up back at CO2 and water. As you can see in this video over-oxidation can be a real concern.  This paper demonstrates the use of a polyoxometalate (POM) catalyst to promote the oxidation of biomass to formic acid.

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How Robots Can Help Us Understand the Environmental Fate of Nanoparticles

“Assessment of the physico-chemical behavior of titanium dioxide nanoparticles in aquatic environments using multi-dimensional parameter testing” von der Kammer, F.; Ottofuelling, S.; Hofmann, T. Environ. Pollut. 2010, 158, 3472-3481. DOI: 10.1016/j.envpol.2010.05.007

In order to rationally design nanoparticles that are environmentally benign, we need to be able to accurately predict their environmental fate (i.e. will they travel long distances through waterways, get stuck in soils or sediments, etc?).  Though relatively robust modeling tools are available for predicting the environmental fate of organic chemicals, analogous tools for nanoparticles are in their infancy.  This is largely due to the insane variety of nanoparticle properties (e.g., composition, size, shape, surface chemistry, etc) that can be varied, resulting in an equally insane variety of nanoparticles to study.  In addition, we know very little about any of these nanoparticles.  One important property that controls the environmental fate of nanoparticles is their propensity to aggregate together and fall out of suspension, potentially limiting their environmental mobility.

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Iron-catalyzed intermolecular cycloaddition

“Iron-catalyzed Intermolecular [2π-2π] Cycloaddition” Russell, S. K.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2011, 133, 8858-8861. DOI: 10.1021/ja202992p

As the cost of precious metals increases dramatically along with concerns over the toxicity of 2nd and 3rd row metals, chemists are increasingly turning to employing earth-abundant metals in catalysis, especially iron.

In their recent contribution in the area of base metal catalysis, the Chirik group at Princeton reports an intermolecular, iron-catalyzed cycloaddition reaction. In addition to building on the intramolecular version of the reaction they had previously reported, the current contribution is also notable for their isolation of a catalytically competent intermediate.

The chemistry starts with their remarkable iron bis(dinitrogen) complex 1 (or a related bridging diiron dinitrogen complex), a formally zero-valent compound with an electronic structure better described as a dianionic bis(imino)pyridine ligand bound to an intermediate spin iron(II) ion.

The redox non-innocence of the supporting ligand enables the iron center to do two electron chemistry (required for oxidative addition and reductive elimination), reactions usually reserved for 2nd and 3rd row transition metals. In Chirik’s system, iron generally stays in the preferred ferrous oxidation state, while the ligand undergoes two electron reactions cycling between a neutral donor and a dianionic form during catalysis.

The bond-making and bond-breaking events still occur at the metal center (as for more traditional organometallic reactions, think Pd(0)/Pd(II) chemistry), the trick is that the accompanying redox changes occur at the ligand.

The bis(dinitrogen) complex 1 can catalyze the intermolecular cycloaddition of 1,3-butadiene with ethylene to form vinylcyclobutane. By introducing a methyl group into the butadiene substrate (isoprene), the 1,4 addition product is formed instead.

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Direct, aerobic arene olefination

“Ligand-Enabled Reactivity and Selectivity in a Synthetically Versatile Aryl C–H Olefination”  Wang, D.-H.; Engle, K. M.; Shi, B.-F. and Yu, J.-QScience 2010327, 315-319. DOI: 10.1126/science.1182512

“Highly Convergent Total Synthesis of (+)-Lithospermic Acid via a Late-Stage Intermolecular C–H Olefination” Wang, D.-H. and Yu, J.-QJ. Am. Chem. Soc. 2011, 133, 5767-5769.  DOI: 10.1021/ja2010225

The Mizoroki-Heck reaction is a widely-used method for cross-coupling of the C-X bond of aryl halides/pseudo-halides with the C-H bond of an olefin – the reaction is so popular that Richard Heck won a share of the 2010 Chemistry Nobel for palladium cross-coupling.   An equivalent of H-X is produced as a byproduct, which is typically neutralized by the addition of stoichiometric base.

A direct coupling of two C-H bonds is an interesting and potentially green alternative to this reaction, since it could simplify the synthesis of the halide coupling partner (shorter synthesis = less waste) and improve the reaction’s atom economy.  In this sort of reaction a directing group is typically needed so the functionalization occurs at only one of the many aryl C-H positions.  Additionally, an oxidant is needed in the catalytic cycle because the metal catalyst, typically Pd(II), is reduced when it mediates the C-C coupling (this sort of mechanism has been proposed).  Typically silver or copper salts are used in superstoichiometric amounts for this purpose.  From a Green Chemistry perspective this is only a marginal improvement over the original Heck reaction – using several equivalents of a transition metal oxidant isn’t a real improvement over generating an equivalent of neutralized acid (like triethylammonium chloride).

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Catalytic Directing Groups in Hydroformylation

“Synthesis of Quaternary Carbon Centers via Hydroformylation”  Sun, X.; Frimpong, K.; Tan, K. L. J. Am. Chem. Soc. 2010, 132, 11841.  DOI: 10.1021/ja1036226

Just as the advent of protecting groups opened up new chemical space accessible by current synthetic techniques, so too did the advent of the directing group.  Both however come with the downside of often requiring additional synthetic steps for the installation and removal of these groups.  For example, the past decade or so has seen a number of efforts at using directing groups such as phosphines to affect the course of hydroformylation reactions.  I should mention here that people are so interested in the hydroformylation of alkenes in part because it is such an industrially important reaction, with 9 million tons of aldehyde products being produced in this way per year (ref).  The challenges with this reaction are selectivity, one of the foremost issues being that terminal alkenes preferentially give linear products.  Shown below is a 2001 example from the Leighton group where a phosphine directing group on allylic ethers yields the branched hydroformylation product (Markovnikov addition), whereas the linear product (anti-Markovnikov) would be favored in the absence of the directing group:

The Up-Side: this method offers access to substrates not previously available through hydroformylation.   The Down-Side: it is hard to imagine an industrially-relevant product containing that specific phosphine moiety, so it would undoubtedly have to be cleaved, making the overall process highly atom un-economical.  This latter point could be addressed by somehow using the phosphine group in a catalytic, instead of stoichiometric, fashion.  This is exactly what the research group of Kian Tan at Boston College has been up to lately.  They have developed what they term a “scaffolding ligand” that coordinates to the organometallic catalyst as well as rapidly and reversibly (two important things for this type of catalysis) forms covalent bonds with alcohols.  In doing so it brings the substrate (in blue below) and catalyst (in red below) in close proximity and influences the course of the reaction.

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