Nav: Home

Nitrogen gets in the fast lane for chemical synthesis

February 08, 2019

HOUSTON - (Feb. 8, 2019) - Rice University scientists have given organic chemists a boost with their latest discovery of a one-step method to add nitrogen to compounds for drugs, pesticides, fertilizers and other products.

Rice synthetic organic chemist László Kürti said the method, reported in the Journal of the American Chemical Society, is a major step forward as it quickens and boosts the yield of valuable molecules known as alpha-aminoketones.

Ketones are carbon-based compounds found in nature and important feedstocks for the chemical industry. The primary amino group (NH2) is a functional group present in many important chemical products. It contains one nitrogen atom and two hydrogen atoms. When a ketone is functionalized with a primary amino group at the alpha carbon, it forms a compound called a primary alpha-aminoketone.

"It's a good precursor, because there's no extra functionalization, like an acyl group, on the NH2 and it can then be converted to whatever you want," said Kürti, an associate professor of chemistry. "Previously, this was the issue: People would put nitrogen in there with extra functionality, but the further processing necessary to get to a free NH2 was complicated."

Postdoctoral researcher Zhe Zhou discovered the reaction when he mixed a silyl enol ether and a nitrogen source in a common solvent, hexafluoroisopropanol, at room temperature and found that it mimicked Rubottom oxidation, an established technique to oxidize enol ethers.

"Oxygen is routinely put into the alpha position," Kürti said. "But nitrogen, no. We are the first to show this is possible in a large number of substrates, and it's simple. It turns out that the solvent itself catalyzes the reaction."

Zhou and co-author and postdoctoral researcher Qing-Qing Cheng refined the method and subsequently tested it by making 19 aminoketones, including three synthetic amino acid precursors. "These unnatural amino acids are significant for drug design," Kürti said. "The enzymatic processes in living organisms are not going to attack them, because they don't fit in the enzymes' pockets."

"Before we had this process, it wasn't impossible to make these kinds of structures," Zhou said. "It was just very complicated and took many steps. The goal, generally, is to get them by the most direct method possible."

Earlier synthetic processes by the Kürti lab eliminated the need for transition metal-based catalysts in the manufacture of amines in order to simplify the usual and often inefficient trial-and-error approach involved in making new chemical compounds like drugs. Metal-based catalysts that speed up amination - the introduction of amine groups to an organic molecule -- can also contaminate the product, so the new process avoids them as well.

"Our amination method promises to replace a common three-step process to make alpha-aminoketones, and the yield, comparably, is very good," Zhou said. "In the standard process, each step cuts the yield, so one-step process is still superior even if the yields are identical, because it takes less time and there's less risk of something going wrong.

"The last thing you want is to get eight steps from the beginning and then ruin it on the ninth because the conditions are not selective enough," he said. "Cutting steps is always beneficial in organic synthesis."

Kürti was delighted to see his social media accounts light up with congratulations from peers and industrial acquaintances upon publication of the paper.

"There's a new trend toward late-stage functionalization, where companies with an existing library of compounds can take 100 of them and perform an additional step to make 100 new compounds," he said. "So from an intellectual property perspective, our discovery is a great gift to industry. This really is a gem of a find."
-end-
The National Institutes of Health, the National Science Foundation, the Robert A. Welch Foundation and Rice University supported the research.

Read the abstract at https://pubs.acs.org/doi/10.1021/jacs.8b13818.

This news release can be found online at https://news.rice.edu/2019/02/08/nitrogen-gets-in-the-fast-lane-for-chemical-synthesis/

Follow Rice News and Media Relations via Twitter @RiceUNews.

Related materials:


Chemists make strides to simplify drug design and synthesis: http://news.rice.edu/2016/09/12/chemists-make-strides-to-simplify-drug-design-and-synthesis/

Rice scientists simplify the incorporation of nitrogen into molecules: http://news.rice.edu/2017/07/12/rice-scientists-simplify-the-incorporation-of-nitrogen-into-molecules-2/

Greener molecular intermediates may aid drug design: http://news.rice.edu/2017/07/05/greener-molecular-intermediates-may-aid-drug-design-2/

Kürti Research Group: http://kurtilabs.com

Rice Department of Chemistry: https://chemistry.rice.edu

Wiess School of Natural Sciences: https://naturalsciences.rice.edu

Images for download:

https://news-network.rice.edu/news/files/2019/02/0211_KETONES-1-web-26cexaq.jpeg Rice University chemists have discovered a one-step method to turn silicon-based silyl enol ether into nitrogen-bearing alpha-aminoketones, valuable building blocks in chemical design. (Credit: Illustration by Zhe Zhou/Rice University)

https://news-network.rice.edu/news/files/2019/02/0211_KETONES-2-web-2c5xbms.jpg

Rice University postdoctoral researcher Zhe Zhou is lead author of a paper on the discovery of a one-step method to turn silicon-based silyl enol ether into nitrogen-bearing alpha-aminoketones, valuable building blocks in chemical design. (Credit: Jeff Fitlow/Rice University)

https://news-network.rice.edu/news/files/2019/02/0211_KETONES-3-web-28ffjza.jpg

A one-step method by synthetic organic chemists at Rice University allows nitrogen atoms to be added to precursor compounds used in the design and manufacture of drugs, pesticides, fertilizers and other products. (Credit: Jeff Fitlow/Rice University)

https://news-network.rice.edu/news/files/2019/02/0211_KETONES-4-web-1yjlx9d.jpg

Rice University researchers László Kürti, left, and Zhe Zhou led an effort to develop a one-step method that allows nitrogen atoms to be added to precursor compounds used in the design and manufacture of drugs, pesticides, fertilizers and other products. (Credit: Jeff Fitlow/Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,962 undergraduates and 3,027 graduate students, Rice's undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 2 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/RiceUniversityoverview. Jeff Falk 713-348-6775 jfalk@rice.edu

Mike Williams 713-348-6728 mikewilliams@rice.edu

Rice University

Related Nitrogen Articles:

'Black nitrogen'
In the periodic table of elements there is one golden rule for carbon, oxygen, and other light elements.
A deep dive into better understanding nitrogen impacts
This special issue presents a selection of 13 papers that advance our understanding of cascading consequences of reactive nitrogen species along their emission, transport, deposition, and the impacts in the atmosphere.
How does an increase in nitrogen application affect grasslands?
The 'PaNDiv' experiment, established by researchers of the University of Bern on a 3000 m2 field site, is the largest biodiversity-ecosystem functioning experiment in Switzerland and aims to better understand how increases in nitrogen affect grasslands.
Reducing reliance on nitrogen fertilizers with biological nitrogen fixation
Crop yields have increased substantially over the past decades, occurring alongside the increasing use of nitrogen fertilizer.
Flushing nitrogen from seawater-based toilets
With about half the world's population living close to the coast, using seawater to flush toilets could be possible with a salt-tolerant bacterium.
We must wake up to devastating impact of nitrogen, say scientists
More than 150 top international scientists are calling on the world to take urgent action on nitrogen pollution, to tackle the widespread harm it is causing to humans, wildlife and the planet.
How nitrogen-fixing bacteria sense iron
New research reveals how nitrogen-fixing bacteria sense iron - an essential but deadly micronutrient.
Corals take control of nitrogen recycling
Corals use sugar from their symbiotic algal partners to control them by recycling nitrogen from their own ammonium waste.
Foraging for nitrogen
As sessile organisms, plants rely on their ability to adapt the development and growth of their roots in response to changing nutrient conditions.
Inert nitrogen forced to react with itself
Direct coupling of two molecules of nitrogen: chemists from Würzburg and Frankfurt have achieved what was thought to be impossible.
More Nitrogen News and Nitrogen Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.