Heterocyclic Chemistry: Properties of Saturated Heterocyclic Compounds
In this section, we will continue to see into the properties of heterocylic compounds using the information about its bonding and structure. Besides that, in this section will mainly discuss about its basicity.
To begin with, we will see firstly about N-heterocylces compounds and immediately we can identify its lone pair electrons which can act as a nucleophile. For example, 5-membered pyrrolidone reacts with a ketone to form an enamine which can be used to synthesis 1,4 dicarbonyl compound as shown below.
The mechanism of the formation of enamine is shown below.
The lone pair electrons in N atom also has consequence that this molecule is a base. The measurement of the basicity of N-heterocycles can be seen from the pKa of its conjugate acid. The example of piperidine has pKa of its conjugate acid is 11.1 and this is quite reasonable for a base.
This reasonable value is due to the lone pair electrons on N atom are in sp3 hybrid orbital which makes it available for protonation. The substituent of N-heterocylces and the ring size could also effect the pKa value. For example, a 6-membered ring morpholine with O atom replacing one of C atom has pKa of its conjugate acid is 8.4 and this means morpholine is not a better base than piperidine, even the ring size is ther same.
This decreasing power of basicity is due to the high electronegativity of O which makes the lone pair electrons on N less available for protonation. This is caused by σ inductive effect of O which pulls the electron of N.
Another case of ring size which also affects the basicity of N-heterocycles as shown by 3-membered ring aziridine.
The pKa of aziridine's conjugate acid is 8.0 which much lower than piperidine which is 11.1 (remember, this is a log scale) which implies aziridine is less basic than piperidine and this is caused by the ring strained in aziridine. In aziridine, all atoms are sp3 hybridised which means the ideal angle is around 109° and this ring the angle is forced to 60°. The way the bonding scheme compensate this ring strained is by increasing its p-character for the bonding within the ring which also has a consequence increasing s-character in the bonding outside the ring. This makes the lone pair electron has more s-character which makes the electrons are held closer to the nucleus. Therefore, the electrons are less available for protonation.
This effect can also be seen in the IR spectroscopy of ν(C=O) in amide. The normal amide such as N,N-dimethylacetamide has ν(C=O) at 1650 cm-1 which is lower than a ketone and this lower frequency is caused by resonance structure due N atom is sp2 hybridised. Comparing with an amide below, the ν(C=O) is 1706 cm-1 which implies it is similar to a ketone rather than an amide.
This is caused by the ring strained which makes the N atom is sp3 hybridised and due to the ring strained the lone pair electrons on N atom has less p-character. Therefore, it has only weak overlap with C=O and this also happens in β-lactam which has ν(C=O) at 1745 cm-1. This ring strained property is the principle action of antibiotic penicillins.
The other prominent heterocylces is O-heterocylcles especially the 3-membered ring epoxides. This strained compound can undergoes ring opening reaction by nucleophiles. Besides that, this ring opening could also be used to synthesis polyethylene glycol with catalyst of Lewis acid.
The 5- and 6-membered ethers are normally unreactive which makes THF is a good coordinating solvent. Besides that, the 6-membered ring THP adopts a chair conformation and also the stereoelectronic effect for axial substitution at anomeric position is observed. This is caused by the overlap between lone pair electrons of O and σ*(C-X) which stabilise the axial position.
To begin with, we will see firstly about N-heterocylces compounds and immediately we can identify its lone pair electrons which can act as a nucleophile. For example, 5-membered pyrrolidone reacts with a ketone to form an enamine which can be used to synthesis 1,4 dicarbonyl compound as shown below.
The lone pair electrons in N atom also has consequence that this molecule is a base. The measurement of the basicity of N-heterocycles can be seen from the pKa of its conjugate acid. The example of piperidine has pKa of its conjugate acid is 11.1 and this is quite reasonable for a base.
Another case of ring size which also affects the basicity of N-heterocycles as shown by 3-membered ring aziridine.
The pKa of aziridine's conjugate acid is 8.0 which much lower than piperidine which is 11.1 (remember, this is a log scale) which implies aziridine is less basic than piperidine and this is caused by the ring strained in aziridine. In aziridine, all atoms are sp3 hybridised which means the ideal angle is around 109° and this ring the angle is forced to 60°. The way the bonding scheme compensate this ring strained is by increasing its p-character for the bonding within the ring which also has a consequence increasing s-character in the bonding outside the ring. This makes the lone pair electron has more s-character which makes the electrons are held closer to the nucleus. Therefore, the electrons are less available for protonation.
This effect can also be seen in the IR spectroscopy of ν(C=O) in amide. The normal amide such as N,N-dimethylacetamide has ν(C=O) at 1650 cm-1 which is lower than a ketone and this lower frequency is caused by resonance structure due N atom is sp2 hybridised. Comparing with an amide below, the ν(C=O) is 1706 cm-1 which implies it is similar to a ketone rather than an amide.
The other prominent heterocylces is O-heterocylcles especially the 3-membered ring epoxides. This strained compound can undergoes ring opening reaction by nucleophiles. Besides that, this ring opening could also be used to synthesis polyethylene glycol with catalyst of Lewis acid.
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