Imine - Formation, Reactions, and Mechanisms

In this article we will discuss Imine compounds in chemistry. Here we will learn about formation, reactions, and mechanisms of imine compounds.

Imine is a chemical compound form as result of condensation of carbonyl compound (ketone or aldehyde) and amine.

Introduction

An imine is a condensation product of carbonyl compound (ketone or aldehyde) and amine.^1,2 The word "imine" was devised by the German chemist Albert Ladenburg (1883).The imines are intermediates in organic synthesis. They are used for the preparation of amines. They are also stable in ionic form which is known as iminium cations.

Figure 1: Imine

Synthesis of imine

Typically, an imine is synthesized by acid catalysed reaction of carbonyl compound and amine.

Figure 2: Synthesis of Imine

The formed imine product can be directly converted to iminium cations by protonation or amine compound by reduction reaction. 

Figure 3: Reactions of Imine

Mechanism of imine formation

1. The mechanism of imine formation consists of following steps;
2. Protonation of carbonyl oxygen to form ionic intermediate
3. Nucleophilic addition on electrophilic carbon
4. Proton transfer
5. Dehydration to form iminium cation.
6. De-protonation of iminium ion to deliver imine product. 

Figure 4: Mechanism of Imine formation

Dehydration of hemiaminals

The imine compounds are synthesized by dehydration of hemiaminal as well. This reaction is generally done by using acid catalyst.

Figure 5: Dehydration of hemiaminal

Mechanism of Dehydration of hemiaminal

The mechanism of dehydration of hemiaminal consists of following steps;

1. Protonation of oxygen to form ionic intermediate
2. Elimination of water molecule to form iminium cation
3. Deprotonation to provide neutral imine product. 

Figure 6: Mechanism of Dehydration of hemiaminal

Reactions of imine

Hydrolysis of imine

The imine compounds are prone to hydrolysis in aqueous acidic condition to produce carbonyl compound and amine. 

Figure 7: Hydrolysis of Imine

Mechanism of hydrolysis of imine

1. Hydrolysis of imine consist of following steps;
2. Protonation of nitrogen to form iminium cation.
3. Nucleophilic addition of water molecule on electrophilic carbon.
4. Proton transfer to form ammonium ion species
5. Leaving of amine moiety to form protonated carbonyl intermediate
6. Finally de-protonation provides carbonyl compound. 

Figure 8: Mechanism of hydrolysis of Imine

Acid-base reactions

Imines acts as base and it reacts with Lewis acids to form iminium salts.

Figure 9: Acid-base reaction of Imine

Reduction reactions

The imines can be reduced be mild reducing agents like sodium cyanoborohydride to produce amine compounds.³ This type of reduction also done by hydrogenation by using H2 gas and Pd/C as catalyst. 

Figure 10: Reduction of Imine

Imine Diels–Alder reaction

Imine can be seen as alkene, hence they are known for their reactivity as dinophile. The imine reacts with the diene to undergo Diels-Alder reaction to form adduct.^4,5

Figure 11: Imine Diels-Alder reaction

Aza-Baylis–Hillman reaction

The N-tosyl imine reacts with a,b-unsaturated ketone to synthesize alkylation product. This reaction is known as Aza-Baylis–Hillman reaction.⁶

Figure 12: Aza-Baylis-Hillman reaction

Mechanism of Aza-Baylis–Hillman reaction

1. The mechanism of Aza-Baylis–Hillman reaction is shown below;
2. Nucleophilic addition of PPh3 onto a,b-unsaturated ketone to form enolate intermediate.
3. Nucleophilic addition of enolate onto imine
4. Protonation of nitrogen atom and generation of alkoxide ion.
5. Proton abstraction at b-carbon to form enolate.
6. Elimination of PPh3 to form a,b-unsaturated ketone.

Figure 13: Mechanism of Aza-Baylis-Hillman reaction

Summary

Friends, in this article we have seen typical methods for the synthesis of imines. Also, we have discussed mechanism and various reactions of imines. 

If you feel this article helpful or if you have any queries regarding this part then please do write in the comment section below. 

That’s all for this topic, we will discuss new question in next blog. Thank you. 

References

1. G. Wittig, A. Hesse (1970). "Directed Aldol Condensations:b Phenylcinnamaldehyde". Organic Syntheses. 50: 66. 
2. https://en.wikipedia.org/wiki/Imine.
3. Cyanohydridoborate anion as a selective reducing agent Richard F. Borch, Mark D. Bernstein, H. Dupont Durst, Journal of the American Chemical Society 1971, 93 (12), 2897-2904.
4. Heintzelman, G. R.; Meigh, I. R.; Mahajan, Y. R.; Weinreb, S. M. (2005). "Diels-Alder Reactions of Imino Dienophiles". Org. React. 65: 141–599. 
5. https://en.wikipedia.org/wiki/Imine_Diels%E2%80%93Alder_reaction
6. Enantioselective aza-Baylis-Hillman Reaction (organic-chemistry.org) https://www.organic-chemistry.org/Highlights/2006/30JanuaryA.shtm.