100-year-old chemistry rule proven false, textbook updates needed

You know that feeling when everyone tells you something is impossible, so you never even try? That is what happened in chemistry for a hundred years. Students memorized a rule, one called Bredt’s rule, and then everyone obeyed it. Professors taught it. Nobody questioned it. And it was wrong.

The team of chemists behind this study didn’t set out to break Bredt’s rule, it just happened.

They made molecules that supposedly couldn’t exist. Not only did they make them – they used them to create novel compounds that could become tomorrow’s medicines.

This is not a tiny correction. It is like learning that you can divide by zero under narrowly defined conditions.

Understanding Bredt’s rule

Back in 1924, Julius Bredt examined certain molecules and concluded it could not happen. He was talking about molecules where two rings connect at a bridge point – the bridgehead.

Bredt argued you cannot place a double bond there in small molecules. The bond would be extremely twisted and break.

For a century, every chemistry textbook repeated this. They called these impossible molecules “anti-Bredt olefins.” Students learned to spot them and cross them out. Case closed.

However, Neil Garg, a distinguished professor of chemistry and biochemistry at UCLA, disagreed. His team went ahead and made these “impossible” molecules anyway.

“People aren’t exploring anti-Bredt olefins because they think they can’t,” Garg pointed out.

Proving Bredt’s rule false

The UCLA team took a strategic approach. They knew these molecules would fall apart quickly, so they never tried to isolate them. Instead, they set up a chemical relay.

When fluoride is added, the molecule expels the leaving group and forms the forbidden, twisted double bond at the bridgehead. Before it can fall apart, another molecule quickly captures it. The sequence happens quickly.

The anti-Bredt olefin exists just long enough to react, then transforms into something stable. It is like crossing hot coals – you keep moving.

Evidence of formation

So how can you prove something existed if it vanished instantly? You look at what is left behind. The products tell the story.

When the team made a twisted molecule with a specific handedness – left-handed versus right-handed – the final product preserved the same twist.

That outcome occurs only if the anti-Bredt olefin formed in between. The molecular fingerprints are consistent with that conclusion.

Computer simulations supported the findings. The calculations predicted what they observed in the lab. When theory and experiment align, the result is compelling.

Medicine needs 3D shapes

This is why drug companies are interested. Many molecules lie relatively flat, but bodies are full of pockets and grooves that need three-dimensional shapes to fit properly. These techniques build molecules with pronounced three-dimensional features.

“There’s a big push in the pharmaceutical industry to develop chemical reactions that give three-dimensional structures like ours because they can be used to discover new medicines,” Garg explained.

Each new shape is a potential key for a biological lock we have not opened yet. The anti-Bredt olefins are doorways to thousands of molecular structures nobody could make before.

Rethinking Bredt’s rule

Bredt was not entirely wrong – his rule works most of the time. But treating it as an unbreakable law was the mistake. Science advances when exceptions are discovered.

“We shouldn’t have rules like this – or if we have them, they should only exist with the constant reminder that they’re guidelines, not rules. It destroys creativity when we have rules that supposedly can’t be overcome,” Garg said.

Now chemistry teachers face an interesting problem. How do you teach something that was “never” but is now “sometimes”? How do you tell students about rules while also telling them to question everything?

The answer is to teach the rule and the exception together. Show how clever chemistry can outsmart the limitations. That is more honest.

What happens next

Labs everywhere are already planning experiments. Some groups want to make new drugs. Others are exploring additional “impossible” molecules. Materials scientists are considering plastics and electronics with novel properties.

“What this study shows is that contrary to one hundred years of conventional wisdom, chemists can make and use anti-Bredt olefins to make value-added products,” Garg noted.

The techniques keep improving. Each successful reaction teaches chemists something new about controlling unstable molecules. Today’s impossibility becomes tomorrow’s routine procedure.

But the real victory is not just about molecules. It is about mindset. When you stop accepting “can’t” as final, you start finding ways around it.

The UCLA team did not discover a new element or invent a new instrument. They simply refused to accept that something was impossible without checking for themselves.

Why does any of this matter?

Most of us are not going to synthesize anti-Bredt olefins in our kitchens. But we all encounter rules that might be more like suggestions.

Sometimes the biggest advances come from people brave enough (or stubborn enough) to test the boundaries.

The chemists did not break physics. They found a path nobody thought to look for. The mountain was still there – they just discovered a tunnel. After a hundred years of going around, someone finally went through.

Next time someone says something is impossible, ask whether anyone has actually tried it recently. You might be surprised by what is possible when you stop assuming and start experimenting.

The full study was published in the journal Science.

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