Noteworthy Chemistry

May 4, 2015

Acetaminophen structure

G. C. Machado and colleagues at the University of Sydney, St. Vincent’s Hospital, the University of New South Wales, and Concord Hospital (all in Sydney, Australia) conducted a systematic review of the safety and efficacy of acetaminophen for pain management in patients with osteoarthritis or nonspecific back pain. Their data meta-analysis encompassed more than 5300 patients and covered 10 randomized controlled trials in which acetaminophen was given to treat hip or knee osteoarthritis and 3 randomized controlled trials in which it was given to treat lower back pain.

The review showed that acetaminophen had no short-term effect on the pain intensity, disability status, or quality of life of individuals who suffered from lower back pain. For those who suffered from hip or knee osteoarthritis, acetaminophen had a statistically significant, but not clinically meaningful, benefit for reducing short-term pain and disability as compared with the placebo. There was no difference between the acetaminophen and control groups in the number of patients reporting adverse effects, but people who took acetaminophen were almost 4 times more likely to have abnormal liver function tests results.

Given their findings, the authors suggest that clinical guidelines for recommending acetaminophen for lower back pain and hip and knee osteoarthritis be reconsidered. Those who suffer from osteoarthritis, however, should take heart: The authors found that strengthening exercises are much more effective at pain reduction than acetaminophen. (BMJ DOI: 10.1136/bmj.h1225; Abigail Druck Shudofsky)

*Paracetamol outside the United States and some other countries

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Is the catalytic pyrolysis of biomass worth pursuing? Converting biomass to biofuel is expected to provide inexpensive, green alternative energy sources. Of all biomass conversion methods, pyrolysis (anaerobic thermochemical treatment) is the most straightforward and most widely studied. Uncatalyzed, rapid pyrolysis can transform biomass into organic liquids, but the product mixture is too complex to be used in any application more advanced than combustion.

Catalytic pyrolysis may enhance the outcome of thermochemical conversions by providing preferred reaction pathways, especially by removing reactive oxygenates. After more than three decades since the initial studies on catalytic pyrolysis, however, the question arises: Has it delivered on its promise?

R. H. Venderbosch at BTG Biomass Technology Group BV (Enschede, The Netherlands) reviewed the progress of catalytic pyrolysis. He conducted a comprehensive analysis of liquids yield relative to quality (in terms of deoxygenation) based on a large body of research literature and experimental data.

The author points out that the formation of coke (carbon deposited on catalyst surfaces) prevents the transformation of biomass to useful yields of the desired hydrocarbons. Moreover, although catalytic pyrolysis can yield products with lower oxygen content than its uncatalyzed counterpart, full deoxygenation has rarely been accomplished experimentally.

In addition to coke, much of the biomass is converted to gas and water. These findings suggest that catalytic pyrolysis might not be the most efficient route to oxygen-free organic liquids. (ChemSusChem DOI: 10.1002/cssc.201500115; Xin Su)

[This week’s Patent Watch discusses subsequent hydrogenation as a way to upgrade heterogeneous catalytic pyrolysis products.—Ed.]

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An axially chiral polymer emits circularly polarized luminescence. Many polymers that contain asymmetric carbon atoms emit circularly polarized luminescence (CPL). But in contrast to polymers with atom chirality, examples of CPL-emitting polymers with axial chirality are rare.

Y. Cheng. C. Zhu, and co-workers at Nanjing University (China) designed and synthesized a series of conjugated polymers (14 in the figure) that contain (R)-binaphthylene and tetraphenylethylene (TPE) units. The binaphthylene groups have axial chirality; the TPE units impart aggregation-induced emission (AIE) to the polymers. The researchers found that only the polymer with the “right” structure (1) exhibited CPL activity.

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Axially chiral and AIE-active polymers

All of the polymers display AIE effects because of TPE units embedded in the polymer chains. In solution, all are CPL-inactive; but when polymer 1 aggregates in aqueous mixtures, it alone becomes CPL-active. This finding indicates that the CPL effect is sensitive to a subtle variations in polymer structure.

The aggregation-induced CPL effect of 1 can be tuned by varying the water content of the solution. The macromolecules of 1 self-assemble into helical nanofibers when they aggregate, whereas the other three polymers do not. The authors conclude that CPL activity correlates with the helical structure of the assembly. (Polym. Chem. DOI: 10.1039/C4PY01689K; Ben Zhong Tang)

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A nanowire–bacteria hybrid achieves artificial photosynthesis. For millions of years, plants have used solar power to produce value-added biochemicals from carbon dioxide and water. The inability of the enzymes that catalyze CO2 reduction to self-repair outside of a cellular environment has hindered attempts to replicate this process artificially. These enzymes often do not tolerate oxygen, which limits their use with CO2 sources such as flue gas. Selecting biosynthetic intermediates to use as building blocks also has been difficult.

M. C. Y. Chang, P. Yang, and colleagues at the University of California, Berkeley; Lawrence Berkeley National Laboratory; and Kavli Energy NanoSciences Institute (Berkeley) developed a biocompatible nanowire array that captures sunlight and provides a direct interface with microbial colonies. They used this system to produce acetic acid, which they then converted to precursors of fuels, polymers, and pharmaceutical compounds.

Solar-powered CO2 fixation process

A photoanode array made of titanium dioxide nanowires collects ultraviolet light and releases electrons to a silicon nanowire photocathode array. A colony of the anaerobic bacterium Sporomusa ovata forms an interconnected network in the local anaerobic environment created by the photocathode array. Buffered brackish water containing trace amounts of vitamins is used as a culture medium. An ion-conductive membrane between the anode and cathode separates the reaction products. Platinum is used as an electrocatalyst to reduce oxygen in the feed gas.

The S. ovata colony reduces CO2 and water to acetic acid at ambient temperature at a rate comparable with that of conventional gas-phase catalysts operating at temperatures >100 ºC. With an inorganic electrolyte, the acetic acid titer is ≈20 mM within 5 days; and it can reach >100 mM in an M9-MOPS medium (Teknova, Hollister, CA). Some efficiency is lost when the source gas contains oxygen, but this can be mitigated by improving the design of the nanowire–bacteria hybrid.

As a proof of concept, specific strains of genetically engineered Escherichia coli (housed in a separate reactor) were used to convert the acetic acid to acetyl coenzyme A. This enzyme served as a building block to form 1-butanol, poly(hydroxybutyrate) polymer, and three natural isoprenoid compounds (amorphadiene, epiaristolochene, and cadinene). (Nano Lett. DOI: 10.1021/acs.nanolett.5b01254; Nancy McGuire)

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The choice of base affects downstream processing. M. E. Kopach and co-workers at Eli Lilly (Indianapolis) and Elanco External Manufacturing & Commercialization (Greenfield, IN) developed a more efficient route to a regulatory starting material for edivoxetine hydrochloride, a developmental ADHD (attention deficit hyperactivity disorder) drug. In the third step of the process, potassium (S)-(–)-2,3-epoxypropanoate reacts with the sulfate salt of N-benzylethanolamine under basic conditions in methanol solvent to form a chiral carboxylate–sulfate bis-salt.

The authors evaluated sodium and potassium bases and found that the workup behavior of the bis-salt depends on the choice of base. Desolvation of the mixed sodium–potassium salt could not reduce the solvent to <2 wt% even at temperatures as high as 60 ºC. The 2 wt% target, however, was achieved for the dipotassium salt. Potassium methoxide was chosen for the transformation. (Org. Process Res. Dev. DOI: 10.1021/acs.oprd.5b00014; Will Watson)

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Dithiooxamide is an odorless thiolating reagent. Carbon–sulfur bonds are found in many biologically important compounds. These compounds are usually prepared with thiol reagents, which are foul-smelling and often require harsh reaction conditions.

H. Firouzabadi, N. Iranpoor, and co-workers at Shiraz University (Iran) report the use of dithiooxamide (1 in the figure), a solid, stable, odorless, commercially available compound, as a thiolating agent. By using PEG200–H2O as the solvent and sodium hydroxide as the base at 35 ºC, they prepared dialkyl and dibenzyl sulfides from the corresponding halides (reaction A). PEG200 is poly(ethylene glycol) with 200 ethylene oxide units.

Thiolation reactions with dithiooxamide

Aromatic iodides and bromides also can be used as substrates if copper(I) iodide is used as a catalyst and the temperature is increased to 120 ºC (reaction B). With an α,β-unsaturated substrate, a thia-Michael reaction takes place (reaction C; EWG is an electron-withdrawing group).

The authors show that their procedure compares well with the use of other sulfur surrogates. They propose mechanisms for the uncatalyzed and catalyzed reactions. The reaction workup proceeds almost odor-free. The reactions were scaled up to 100 mmol. (Eur. J. Org. Chem. DOI: 10.1002/ejoc.201500156; José C. Barros)

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