Step-by-Step Guide to the Inversion Reaction Mechanism
Inversion is the process of shifting the molecule orientation by 180 degrees angle of a chiral centre in a molecule during a chemical reaction. Since a molecule can form two enantiomeric forms around a chiral nucleus, the Walden inversion shifts the configuration of a molecule from one enantiomeric form to the other. In an SN2 reaction, for example, Walden inversion occurs at a tetrahedral carbon atom. To get a sense of it, imagine an umbrella turned inside out in a gale. The Walden inversion occurs when the nucleophile attacks the backside of the reactant in an SN2 reaction, resulting in a product with the opposite structure as the reactant. As a consequence, during the SN2 reaction, the product inversion is 100%. This is known as Walden inversion.
In 1896, chemist Paul Walden was the first to find it. He was able to convert one enantiomer of a chemical compound into the other enantiomer and back in a so-called Walden loop:
Chlorosuccinic acid was converted to malic acid (+).
The hydroxyl group (OH) was substituted by chlorine molecules to the other isomer of chlorosuccinic acid in the next step by silver oxide in water molecules with configuration retention.
A second reaction with silver oxide (AgO) yielded (-) malic acid after a reaction with phosphorus pentachloride (PCl₅).
After that, a second reaction with PCl₅ (phosphorus pentachloride) brought the cycle back to where it started.
Reaction Showing Inversion
1. The silver oxide acts as a hydroxide donor in the first step of the reaction shown below, while the silver ion has no effect. The carboxyl dianion A undergoes intramolecular nucleophilic substitution by the carboxylate anion (COO-), resulting in the formation of a four-membered lactone ring B. While the carboxyl group is reactive as well, in silico data indicates that the transition state for the formation of the three-membered lactone is extremely strong. The lactone is opened by a hydroxide ion ring to form the alcohol C, and the net result of two counts of inversion is configuration retention.
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2. Nitrogen Inversion
In chemistry, nitrogen inversion (also known as umbrella inversion) is a fluxional phase in which the molecule "turns inside out" in nitrogen and amines. It's a rapid oscillation of the nitrogen atom and its substituents, with the nitrogen "running" through the plane created by the substituents (though the substituents still shift, but in the opposite direction); the molecule is in a planar transition state.
Nitrogen inversion provides a low-energy mechanism for racemization for a compound that would otherwise be chiral due to a nitrogen stereocenter, rendering chiral resolution unlikely.
Nitrogen inversion is a form of pyramidal inversion that affects carbanions, phosphines, arsines, stibines, and sulfoxides, among other things.
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Energy Barrier in Inversion Process
At room temperature, the ammonia interconversion is extremely fast, inverting 30 billion times per second. The rapidity of the inversion is due to two factors: a low energy barrier (24.2 kJ/mol; 5.8 kcal/mol) and the barrier's narrow width, which allows for regular quantum tunnelling. At room temperature, however, phosphine (PH3) inverts very slowly (energy barrier: 132 kJ/mol).
Quantum Effect on Inversion Process
Quantum tunnelling occurs in ammonia due to a thin tunnelling barrier rather than thermal excitation. Energy level splitting occurs when two states are superimposed, which is used in ammonia masers.
Mechanism of Inversion
When an organic compound undergoes a Nucleophilic substitution reaction through the SN2 mechanism, inversion of configuration is common.
A Nucleophile (an electron-rich species with an affinity for an electron-deficient centre) may strike the Stereocenter from both the front and back sides.
The nucleophile attacks the stereocenter from the same side as the leaving party in a frontside assault. This results in Configuration Retention. During a chemical reaction or transformation, retention of configuration refers to the continuity of the spatial arrangement of bonds to an asymmetric core. With the help of an example, it's easy to understand:
The nucleophile strikes the stereocenter from the opposite side of the leaving party in a backside attack. As a consequence, a product with Inversion Of Configuration is developed.
Consider the following equation to understand how Retention of Configuration and Inversion of Configuration occur in an organic molecule undergoing nucleophilic substitution.
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The nucleophile strikes the stereocenter from the opposite side of the leaving party in a backside attack. As a consequence, a product with Inversion Of Configuration is developed.
Consider the following equation to understand how Retention of Configuration and Inversion of Configuration occur in an organic molecule undergoing nucleophilic substitution.
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The incoming nucleophile ‘Y' targeting the stereocenter Carbon here substitutes for halogen.
a) On the one hand, ‘Y' attacks from the front, resulting in a product with Retention Of Configuration as shown in structure A,
b) On the other hand, ‘Y' attacks from the back, resulting in a product with Inversion Of Configuration as shown in structure B.
Let's take a closer look at the SN2 reaction, which causes Inversion Of Configuration.
Nucleophilic Substitution-Bimolecular Reaction Mechanism (SN2)
This form of nucleophilic substitution reaction has a second order kinetics, which means that the
rate is determined by the concentrations of both the nucleophile and the haloalkane.
Rate = K [ R-X] [-OH]
Order = 1+1 = 2 (sum of power of concentration terms in rate law)
Some Important Features of SN2 Mechanism
1.The reaction will be completed in a single step, which will be the Rate Determining Step. As a result, it is classified as 2nd order kinetics.
2.The configuration is inverted.
3.There is no carbocation formation. However, the creation of the transition state is involved.
4.The SN2 mechanism is favoured by the presence of a primary alkyl group and a nonpolar solvent.
Hydrolysis of Sucrose
Sucrose is converted to glucose and fructose after hydrolysis breaks the glycosidic bond. However, since hydrolysis is so sluggish, sucrose solutions can sit for years with little change. However, if the enzyme sucrase is added, the reaction will proceed quickly. Hydrolysis can also be accelerated by using weak acids like cream of tartar or lemon juice. Similarly, during digestion, gastric acidity transforms sucrose to glucose and fructose, with an acetal bond between them that can be broken by an acid.
Hydrolysis releases about 1.0 kcal (4.2 kJ) per mole of sucrose, or about 3 small calories per gramme of substance, given (higher) heats of combustion of 1349.6 kcal/mol for sucrose, 673.0 for glucose, and 675.6 for fructose.
Let's look at why the hydrolysis of sucrose is called inversion. Sucrose has a dextrorotatory effect. However, following the hydrolysis reaction, glucose (which is dextrorotatory) and fructose (which is laevorotatory) are formed. As a result, sucrose hydrolysis is an inversion reaction.
C₁₂H₂₂O₁₁ + H₂O \[\xrightarrow[\Delta ]{H}\] C₆H₁₂O₆ + C₆H₁₂O₆
Sucrose D-(+)-Glucose D-(-)-Fructose
Did You Know that?
In 1934, microwave spectroscopy was used for the first time to detect ammonia inversion.
In one analysis, putting the nitrogen atom near a phenolic alcohol group delayed the inversion of an aziridine by a factor of 50 relative to the oxidised hydroquinone. The device interconverts through oxygen oxidation and sodium dithionite reduction.
FAQs on Inversion Chemical Reaction Explained
1. What is meant by inversion of configuration in a chemical reaction?
Inversion of configuration refers to the spatial rearrangement of atoms or groups around a chiral centre during a chemical reaction. This results in a product molecule whose configuration is the mirror image of the original reactant. A common analogy is an umbrella flipping inside out in strong wind, where the overall structure is inverted. If the reactant has an 'R' configuration, the product will have an 'S' configuration, and vice-versa.
2. How does inversion of configuration occur in an SN2 reaction?
Inversion is a hallmark of the SN2 (bimolecular nucleophilic substitution) mechanism. It occurs because the incoming nucleophile attacks the carbon atom from the side directly opposite to the leaving group. This is called backside attack. As the nucleophile forms a bond and the leaving group departs, the other three groups attached to the carbon atom are pushed to the other side, causing a complete inversion of the molecule's stereochemistry.
3. Why is the hydrolysis of sucrose called an 'inversion' reaction?
This use of 'inversion' refers to the change in optical rotation, not configuration. Sucrose is dextrorotatory, meaning it rotates plane-polarised light to the right (+66.5°). Upon hydrolysis, it breaks down into a mixture of glucose (+52.5°) and fructose (-92.4°). The resulting mixture is laevorotatory (net rotation is to the left). Because the direction of optical rotation 'inverts' from positive to negative, the process is called the inversion of sucrose.
4. What is the difference between inversion and retention of configuration?
The key difference lies in the spatial arrangement of the product relative to the reactant:
- Inversion of Configuration: The product has a stereochemical configuration that is the mirror image of the reactant. This is characteristic of SN2 reactions.
- Retention of Configuration: The product has the exact same spatial arrangement of groups around the chiral centre as the reactant. The bonds in the reactant are not broken at the chiral centre during the reaction.
5. What is Walden Inversion?
Walden inversion is the specific phenomenon of the inversion of a chiral centre in a molecule during a chemical reaction. The term is named after chemist Paul Walden, who first observed this process in 1896. He demonstrated that he could convert one enantiomer of a compound into its other enantiomer through a cycle of reactions, which proved that nucleophilic substitution at a chiral centre could cause the configuration to flip.
6. What is the main stereochemical consequence of an inversion reaction?
The primary stereochemical consequence of an inversion reaction is the formation of a single enantiomer that is opposite to the reactant's configuration. For example, if you start with a pure sample of (R)-2-bromooctane and react it via an SN2 mechanism, you will obtain a pure sample of (S)-2-octanol. This predictability and stereospecificity are crucial in synthetic chemistry for creating molecules with a desired 3D structure and biological activity.
