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Yearly Archives: 2010

Learning from past mistakes – Dioxins

“Dioxins: An Overview and History”  Hites, R. A.  Environ. Sci. Technol. 2010, ASAP.  DOI 10.1021/es1013664

One of my main reasons for drinking the green chemistry kool-aid is that I believe it allows me to still do cool chemistry as well as to contribute to building a more sustainable civilization (at least that’s the idea).  The focus, in my eyes, is on the positive things you can do with chemistry.  However, as the Spanish-American philosopher George Santayana first said, “Those who cannot remember the past are condemned to repeat it.”  With that in mind, this post is about one of the most well-studied mistakes in the history of the chemical enterprise, polychlorinated dibenzo-p-dioxins (PCDDs), often referred to collectively in the literature as dioxins.  In Ronald Hites’ recent ES&T feature article on dioxins, he tells the story of the most toxic of the 75 dioxin congeners, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD).

The most sinister aspect of dioxins, from a chemists’ perspective, is the (more…)

Hydrogen-Mediated C-C Coupling to form Allylic Alcohols

“Direct Vinylation of Alcohols or Aldehydes Employing Alkynes as Vinyl Donors: A Ruthenium Catalyzed C-C Bond Forming Transfer Hydrogenation”  Patman, R. L.; Chaulagain, M. R.; Williams, V. M.; Krische, M. J. J. Am. Chem. Soc. 2009131, 2066-2067. DOI: 10.1021/ja809456u

In their 2007 JOC perspective on hydrogen-mediated C-C bond formation, Krische and co-workers point out that “upon consideration of the E-factor for various segments of the chemical industry, a strong inverse correlation between process volume and waste generation is observed.”(1) Given that the lower volume fine chemical and pharmaceutical sectors typically focus on the production of chemicals with higher degrees of molecular complexity then their bulk chemical counterparts, the authors propose that there is a persistent need for the development of selective, atom-economical reactions capable of producing these relatively specialized chemicals. As luck would have it, the Krische group has come to the rescue with a number of reactions that might fit the bill.

One such reaction is their recent report of the ruthenium-catalyzed vinylation of alcohols or aldehydes using alkynes as the vinyl donors (shown above).

I think this reaction is neat because it represents a departure from how people have typically gone about bringing alkynes and alcohols together to form allylic alcohols. In this early example from the Wipf group, (more…)

Presidential Green Chemistry Awards: Codexis/Merck part 2

Savile, Janey, Mundorff, Moore, Tam, Jarvis, Colbeck, Krebber, Fleitz, Brands, Devine, Huisman, and Hughes.  Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture.  Science, 2010, 329, 305-309. DOI: 10.1126/science.1188934.

Here’s a short follow-up on this previous post, which covered a biocatalytic reaction developed by Codexis to make the key intermediate in the synthesis of Merck’s drug montelukast (aka Singulair).  The 2010 Presidential Green Chemistry Awards were just announced, and the award for “Greener Reaction Conditions” went to Merck and Codexis for developing an enantioselective biocatalyst for the synthesis of sitagliptin, Merck’s blockbuster anti-diabetes drug (aka Januvia).  This work is also the subject of a recently-published Science paper from Merck and Codexis.

The paper describes the development of an enzyme-catalyzed replacement for the final reaction in the synthesis of sitagliptin, in which a ketone functionality is converted into an amine. (more…)

From Biomass to Commodity Chemicals

“An efficient didehydroxylation method for the biomass-derived polyols glycerol and erythritol.  Mechanistic studies of a formic acid-mediated deoxygenation” Arceo, E.; Marsden, P.; Bergman, R. G.; Ellman, J. A. Chemical Communications, 2009, 23, 3357. 10.1039/b907746d

Scheme 1, Proposed Conversion of Biomass Into Value Added Chemicals

A major focus in the area of “green” methods development is the mild and selective removal of functionality from readily available bio-derived feed stocks.  Unlike petrochemical derived starting materials, the majority of biomass is highly oxygenated (think carbohydrates or lignin), and before the carbon embedded within this framework can be used for all-purpose chemical manufacturing the oxygen must be removed. (more…)

Do water fleas like the taste of nanoparticles?

“Quantification of Water Solubilized CdSe/ZnS Quantum Dots in Daphnia magna” N. A. Lewinski, H Zhu, H J Jo, D. Pham, R R Kamath, C R Ouyang, C D Vulpe, V L Colvin, and R A Drezek. Environ. Sci. Technol. 2010, 1841-1846. 10.1021/es902728a

“Quantum Dot Weathering Results in Microbial Toxicity” S Mahendra, H Zhu, V L Colvin, P J Alvarez. Environ. Sci. Technol. 2008, 9424-9430. 10.1021/es8023385

Overview of the test subject, technique, and nanoparticles used in these experiments

The goal of green chemistry is to design chemicals and chemical processes which are inherently less toxic. For the emerging discipline of nanoscience, the potential toxicological properties remain largely unknown. That said I would like to discuss two related articles concerning the fate and toxicity of nanoparticles (NPs) in the aquatic environment. I like this set of articles because they are both simple, and yet give a hint of the complexities involved with understanding NP fate and toxicity. The more recent, examines the interaction between CdSe/ZnS NPs with Daphnia (a model species for aquatic toxicity). And the original article that drew my attention to this work concerned the same NP and studies the effect that chemical degradation has on NP toxicity. (more…)

Dioxygen Activation at Low-Valent Silicon

Xiong, Yao, Muller, Kaupp, Driess. From silicon(II)-based dioxygen activation to adducts of elusive dioxasiliranes and sila-ureas stable at room temperature. Nature Chemistry 2010, 2, 577-580. DOI: 10.1038/nchem.666

Metal-free syntheses are currently under intense investigation as potentially cheaper and less-polluting alternatives to reactions involving stoichiometric or catalytic metals. In the Driess group’s recent contribution to Nature Chemistry, they report a silylene compound that activates O2, a biologically and industrially relevant reaction that tends to be associated with transition metals. In addition, they were able to isolate and crystallographically characterize the first dioxasilirane, the silicon-based analogue of the more familiar dioxirane reagents. Importantly, Driess’s dioxasilirane is capable of intramolecular O-atom transfer with the resulting silanone having the shortest silicon-oxygen bond reported to date.


Scalable biocatalytic process for asymmetric reduction in the production of montelukast

Liang, Lalonde, Borup, Mitchell, Mundorff, Trinh, Kochrekar, Cherat, Pai.  Development of a Biocatalytic Process as an Alternative to the (−)-DIP-Cl-Mediated Asymmetric Reduction of a Key Intermediate of Montelukast. Org. Process Res. Dev. 2010, 14, 193-198. DOI: 10.1021/op900272d

This article from researchers at Codexis describes the development of a biocatalytic (i.e. enzyme-catalyzed) method for creating the lone stereocenter in the synthesis of montelukast sodium, aka Merck’s asthma drug Singulair. The original Merck process route includes an enantioselective ketone reduction using a boron reagent derived from alpha-pinene called (-)-DIP-Cl. The reaction works well: high yield, high enantioselectivity (although still requiring a recrystallization step to upgrade from ~95% to 99% ee), and (-)-DIP-Cl is made in one step from cheap starting materials. The downside is that at least 1.5 equivalents of (-)-DIP-Cl must be used, and the reagent is moisture sensitive and corrosive. Codexis, being in the enzyme business, decided to find an enzyme that would catalyze this same reaction. (more…)