Name: why ring nitrogen changes amine basicity
Uploaded: 2023-04-30T10:39:04.000Z
Duration: 1 min 25 s
Channel: JoVE

Die Basizität heterozyklischer Amine wird sowohl durch den Resonanz- als auch durch den Hybridisierungseffekt beeinflusst.
Um den Resonanzeffekt zu verstehen, betrachten Sie zwei aromatische heterozyklische Amine – Pyridin und Pyrrol. Die ungebundenen Elektronen des Pyridin-Stickstoffs befinden sich in einem sp 2-Hybridorbital. Da sie nicht zum aromatischen Sextett beitragen, stehen sie für die Protonierung zur Verfügung.
In Pyrrol liegen die nicht bindenden Elektronen in einem p-Orbital vor und sind Teil des aromatischen π Systems. Hier ist die Protonierung ungünstig, da die Aromatizität in der konjugierten Säure verloren geht.
Da das pKa des protonierten Pyrrols geringer ist als pKa des protonierten Pyridins, ist Pyridin basischer als Pyrrol.
Für den Hybridisierungseffekt ist die Hybridisierung des Aminstickstoffs zu berücksichtigen. Mit zunehmendem prozentualen Charakter werden die ungebundenen Elektronen fester gehalten und stehen weniger für die Protonierung zur Verfügung.
Mit weniger s Charakter des sp3-hybridisierten Piperidinstickstoffs lässt er sich leicht mit einem höheren pK a-Wert der konjugierten Säure protonieren. Somit ist Piperidin basischer als Pyridin.

basizität heterozyklischer aromatischer amine

Basicity of Heterocyclic Aromatic Amines

Heterocyclische Amine, bei denen das N-Atom Teil eines alicyclischen Systems ist, ähneln in ihrer Basizität den Alkylaminen. Interessanterweise weist das heterocyclische Amin mit einem Stickstoffatom als Teil eines aromatischen Rings eine viel geringere Basizität auf als sein entsprechendes alicyclisches Gegenstück. Aus diesem Grund ist Piperidin (pK_b = 2,8) deutlich basischer als Pyridin (pK_b = 8,8), wie in Abbildung 1 dargestellt.

<img alt="Figure1" src="/files/ftp_upload/12527/12527-PT_Figure_1.svg" style="text-align: center; height: 110px;">

Abbildung 1. Der Vergleich der Basizität von Piperidin und Pyridin.

Dieser Basizitätsunterschied kann auf den Hybridisierungszustand von Orbitalen zurückgeführt werden, die ein freies Elektronenpaar am N-Atom enthalten, wie in Abbildung 2 dargestellt. Im Fall von Piperidin befindet sich das freie Elektronenpaar in einem sp^3-hybridisierten Orbital mit niedrigeren s Charakter, wodurch das freie Elektronenpaar besser für die Entfaltung einer Basizität gegenüber Säuren verfügbar wird. Im Gegensatz dazu befindet sich in Piperidin das freie Elektronenpaar in einem sp^2-hybridisierten Orbital mit einem viel höheren s-Charakter. Folglich ist das freie Elektronenpaar fester an den Arylring gebunden und weniger für die Entfaltung einer Basizität gegenüber Säuren verfügbar.

<img alt="Figure2" src="/files/ftp_upload/12527/12527-PT_Figure_2.svg" style="text-align: center; height: 60px;">

Abbildung 2. Die Auswirkung der hybridisierten Orbitale auf die Basizität.

Pyrrol ist viel weniger basisch als Pyridin und hat einen pK_b-Wert von 15. Das in Abbildung 3 gezeigte freie Elektronenpaar am N-Atom befindet sich in einem reinen p-Orbital und ist perfekt auf die p-Orbitale der C-Atome ausgerichtet, die zur Aromatizität des Rings beitragen. Daher wird das freie Elektronenpaar am N-Atom von Pyrrol durch Resonanz im gesamten Ring delokalisiert. Umgekehrt ist das freie Elektronenpaar am N-Atom von Pyridin, das sich in einem sp^2-hybridisierten Orbital befindet, senkrecht zu den anderen sp^2-Orbitalen der an der Resonanz beteiligten C-Atome ausgerichtet. Daher ist das freie Elektronenpaar am N-Atom von Pyridin viel besser verfügbar als das von Pyrrol, was zu einer höheren Basizität von Pyridin führt.

<img alt="Figure3" src="/files/ftp_upload/12527/12527-PT_Figure_3.svg" style="text-align: center; height: 90px;">

Abbildung 3. Die Lewis-Struktur von Pyrrol.

Imidazol enthält zwei N-Atome in einem fünfgliedrigen Ring und ist ein lebenswichtiger Heterocyclus, der in vielen Proteinen vorkommt. Dieses heterozyklische Amin mit einem pK_b-Wert von 7 ist um den Faktor 100 basischer als Pyridin. Das N-Atom, das dem von Pyrrol ähnelt, ist nicht basisch. Das andere N-Atom ist basisch und abstrahiert H von der Säure, wodurch ihre konjugierte Säure entsteht, die durch die Resonanz stabilisiert wird, wie in Abbildung 4 dargestellt. Diese Resonanzstabilisierung der konjugierten Base führt zu einer erhöhten Basizität von Imidazol im Vergleich zu Pyridin.

<img alt="Figure4" src="/files/ftp_upload/12527/12527-PT_Figure_4.svg" style="text-align: center; height: 125px;">

Abbildung 4. Die Resonanzstabilisierung in Imidazoliumionen.

Die Basizität von Aminen bietet ein wertvolles praktisches Hilfsmittel zur Abtrennung von Aminen aus einer Mischung, die andere neutrale Verbindungen enthält. Dies wird erreicht, indem die unreine Mischung in Ether gelöst und in einem Scheidetrichter mit Wasser geschüttelt wird. Nachdem sich die beiden Schichten getrennt haben, werden durch das Ablassen der Wasserschicht das Salz und die meisten anorganischen Verunreinigungen entfernt. Wenn der organischen Schicht verdünnte wässrige Säure zugesetzt wird, werden die Amine selektiv in die entsprechende Säure protoniert und lösen sich in der wässrigen Schicht auf. Durch das Abtropfen der organischen Schicht werden die neutralen organischen Verunreinigungen entfernt. Eine langsame Basifizierung der wässrigen Schicht wird das freie Amin wieder regeneriert, welches anschließend mit einem neuen Volumen Ether extrahiert werden kann. Die anschließende Verdampfung des Ethers ergibt ein reines Amin.

Basizität heterozyklischer aromatischer Amine

Heterocyclische Amine, bei denen das N-Atom Teil eines alicyclischen Systems ist, ähneln in ihrer Basizität den Alkylaminen. Interessanterweise ist das heterocyclische Amin ...

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Organic Chemistry

Organische Chemie

Unit 1

Einheit 1

Amines

Amine

KEY TERMS AND CONCEPTS

KERNBEGRIFFE UND KONZEPTE

why ring nitrogen changes amine basicity

Heterocyclic amines can show very different basicity depending on where the nitrogen atom sits in the ring. When nitrogen is part of an alicyclic ring, the amine behaves much like an alkylamine. When nitrogen is part of an aromatic ring, the compound is usually much less basic than its alicyclic counterpart.

Piperidine and pyridine show this difference clearly. Piperidine is significantly more basic than pyridine, with pKb values of 2.8 and 8.8, respectively. The reason is the orbital that holds the lone pair on nitrogen. In piperidine, the lone pair is in an sp3-hybridized orbital with lower s character, so it is easier to use in reactions with acid. In pyridine, the lone pair is in an sp2-hybridized orbital with higher s character, so it is held more tightly and is less available.

Pyrrole is even less basic than pyridine. Its pKb value is 15. The lone pair on nitrogen is in a pure p orbital, and it lines up with the p orbitals of the carbon atoms in the ring. That lone pair helps the ring stay aromatic, so it is delocalized by resonance. In pyridine, by contrast, the lone pair is in an sp2 orbital that points away from the ring system, so it is much more available for basic behavior.

Imidazole has two nitrogen atoms in a five-membered ring and is found in many proteins. It is more basic than pyridine by a factor of 100, with a pKb of 7. The nitrogen that acts like pyrrole is not basic. The other nitrogen is basic and can accept H from acid. Its conjugate acid is stabilized by resonance, and that stabilization helps explain the higher basicity of imidazole.

The basicity of amines is also useful in the lab for separating amines from neutral compounds. A common method uses ether and water in a separatory funnel. The water layer is drained first to remove the salt and most inorganic impurities. Then dilute aqueous acid is added to the organic layer. The amines become protonated and move into the aqueous layer, while the neutral organic impurity stays behind. The aqueous layer is then basified slowly to regenerate the free amine, which can be extracted with fresh ether and recovered after the ether is evaporated.

Why Ring Nitrogen Changes Amine Basicity

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key terms and concepts

Compare piperidine, pyridine, pyrrole, and imidazole to see how nitrogen placement changes basicity and how amines are separated in the lab.

Why Ring Nitrogen Changes Amine Basicity | JoVE K12

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Why Ring Nitrogen Changes Amine Basicity

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