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

헤테로 고리 아민의 염기성은 공명과 혼성화 효과 모두에 의해 영향을받습니다.
공명 효과를 이해하려면 두 가지 방향족 헤테로사이클릭 아민인 피리딘(pyridine)과 피롤(pyrrole)을 고려하십시오. 피리딘 질소의 결합되지 않은 전자는 sp2 하이브리드 궤도에 존재합니다. 그들은 방향족 섹스텟에 기여하지 않기 때문에 protonation에 사용할 수 있습니다.
pyrrole에서 비결합 전자는 p 궤도에 존재하며 방향족 π 시스템의 일부입니다. 여기서, 양성자화는 공액산에서 방향성(aromaticity)이 손실되기 때문에 바람직하지 않습니다.
양성자화된 피롤의 pKa가 양성자화된 피리딘의 pKa보다 작기 때문에, 피리딘은 피롤보다 염기성이 더 높습니다.
혼성화 효과의 경우 아민 질소의 혼성화를 고려하십시오. 퍼센트 s 특성이 증가함에 따라 결합되지 않은 전자는 더 단단히 고정되고 양성 생성에 사용할 수 있는 시간이 줄어듭니다.
sp3-hybridized piperidine nitrogen의 더 적은 s 특성으로, conjugate acid의 더 높은 pKa 값으로 쉽게 양성자화됩니다. 따라서 피페리딘은 피리딘보다 염기성이 더 높습니다.

헤테로사이클릭 방향족 아민의 염기성

Basicity of Heterocyclic Aromatic Amines

N 원자가 지환족 시스템의 일부인 헤테로고리형 아민은 염기도가 알킬아민과 유사합니다. 흥미롭게도, 방향족 고리의 일부로서 질소 원자를 갖는 헤테로고리형 아민은 상응하는 지환족 대응물보다 염기도가 훨씬 낮습니다. 이러한 이유로 그림 1에 제시된 것처럼 피페리딘(pK_b = 2.8)은 피리딘(pK_b = 8.8)보다 훨씬 더 염기성입니다.

<img alt="Figure1" src="/files/ftp_upload/12527/12527-PT_Figure_1.svg" style="text-align: center; height: 110px;">

Figure 1. 피페리딘과 피리딘의 염기도 비교.

염기도의 이러한 차이는 그림 2에 설명된 것처럼 N 원자에 고립 전자쌍을 포함하는 오비탈의 혼성화 상태에 기인할 수 있습니다. 피페리딘의 경우, 고립 전자쌍은 더 낮은 s를 갖는 sp^3 혼성화된 오비탈에 존재합니다. 특성을 가지므로 고독한 쌍이 산에 대한 염기성을 나타내는 데 더 유용하게 됩니다. 반면, 피페리딘에서는 고독한 쌍이 훨씬 더 높은 s 특성을 포함하는 sp^2 혼성 궤도에 존재합니다. 결과적으로, 고립 전자쌍은 아릴 고리에 더 단단히 결합되어 산에 대한 염기성을 나타내는 데 사용할 수 있는 양이 줄어듭니다.

<img alt="Figure2" src="/files/ftp_upload/12527/12527-PT_Figure_2.svg" style="text-align: center; height: 60px;">

Figure 2. 혼성화된 오비탈이 염기도에 미치는 영향.

피롤은 pK_b 값이 15인 피리딘보다 훨씬 덜 염기성입니다. 그림 3에 표시된 N 원자의 비공유 전자쌍은 순수한 p 오비탈에 있으며 C 원자의 p 오비탈과 완벽하게 정렬되어 있습니다. 반지의 방향성. 따라서 피롤의 N 원자에 있는 고립 전자쌍은 고리 전체에서 공명에 의해 비편재화됩니다. 반대로, sp^2 혼성 궤도에 있는 피리딘의 N 원자에 있는 고립 쌍은 공명에 참여하는 C 원자의 다른 sp^2 궤도에 수직으로 정렬됩니다. 따라서 피리딘의 N 원자에 있는 비공유 전자쌍은 피롤의 비공유 전자쌍보다 훨씬 더 많이 이용 가능하므로 피리딘의 염기도가 더 높아집니다.

<img alt="Figure3" src="/files/ftp_upload/12527/12527-PT_Figure_3.svg" style="text-align: center; height: 90px;">

Figure 3. 피롤의 루이스 구조.

이미다졸은 5원 고리에 2개의 N 원자를 포함하며 많은 단백질에서 발견되는 중요한 헤테로사이클입니다. pK_b가 7인 이 헤테로사이클릭 아민은 피리딘보다 100배 더 염기성입니다. 피롤의 N 원자와 유사한 N 원자는 비염기성입니다. 다른 N 원자는 염기성이며 산에서 H를 추출하여 공액 산을 생성하며 그림 4에 설명된 것처럼 공명에 의해 안정화됩니다. 공액 염기의 공명 안정화로 인해 피리딘에 비해 이미다졸의 염기도가 증가합니다.

<img alt="Figure4" src="/files/ftp_upload/12527/12527-PT_Figure_4.svg" style="text-align: center; height: 125px;">

Figure 4. 이미다졸륨 이온의 공명 안정화.

아민의 염기성은 다른 중성 화합물을 함유한 혼합물에서 아민을 분리하는 귀중한 실용적인 도구를 제공합니다. 이는 불순한 혼합물을 에테르에 용해시키고 분별 깔대기에서 물과 함께 흔들어서 달성됩니다. 두 층이 분리된 후 물 층을 배수하면 염분과 대부분의 무기 불순물이 제거됩니다. 묽은 수성 산을 유기층에 첨가하면 아민이 선택적으로 해당 산으로 양성자화되어 수성층에 용해됩니다. 유기층을 배수하면 중성 유기 불순물이 제거됩니다. 수층의 느린 염기화는 다시 유리 아민을 재생하며, 이는 새로운 양의 에테르를 사용하여 추출할 수 있습니다. 이후 에테르를 증발시키면 순수한 아민이 생성됩니다.

N 원자가 지방환계의 일부인 헤테로사이클릭아민은 알킬아민과 염기성이 유사합니다. 흥미롭게도, 헤테로 고리 아민 ...

Education

교육

JoVE Core

Organic Chemistry

유기 화학

Unit 1

제1단원

Amines

아민

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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

amines: introduction

Amines: Types and Classifications

Amines are organic derivatives of ammonia. They form when one or more ammonia protons are replaced by alkyl or aryl groups. Chemists sort amines by the number of organyl groups attached to the nitrogen atom. Primary amines have one organyl group on nitrogen. Secondary amines have two, and tertiary amines have three. If a fourth organyl group is present, the nitrogen carries a formal positive charge. These compounds are called quaternary ammonium salts. Amines are also grouped as aliphatic or...

nomenclature of primary amines

Naming Primary Amines in Organic Chemistry

Primary amines are named by following a few clear organic chemistry rules. These rules help identify the amino group, written as –NH2, and show how it connects to the carbon chain. Common names for primary amines use the alkyl group name plus the suffix -amine. In IUPAC naming, the final -e of the parent alkane is changed to -amine, which gives an alkanamine name. The longest carbon chain attached to the amine nitrogen is chosen, and the carbon bonded to nitrogen gets the lowest locant. Any...

nomenclature of secondary and tertiary amines

nomenclature-of-secondary-and-tertiary-amines

Naming Secondary, Tertiary, and Quaternary Amines

Secondary and tertiary amines are ammonia derivatives with two or three hydrogen atoms replaced by alkyl groups. They may be symmetrical, with the same alkyl groups attached to nitrogen, or unsymmetrical, with more than one kind of alkyl group present. These compounds are often named as alkylamines in standard naming. For symmetrical secondary and tertiary amines, the prefixes di- and tri- are used. For unsymmetrical amines, each substituent is named and listed in alphabetical order. IUPAC...

nomenclature of aryl and heterocyclic amines

nomenclature-of-aryl-and-heterocyclic-amines

Naming Aniline and Ring Amine Derivatives

Naming aniline and ring amine derivatives follows clear rules for aromatic and heterocyclic amines. The simplest aromatic amine is phenylamine, which has an –NH2 group directly attached to an aromatic ring. The common name for this skeleton is aniline. Functionalized anilines often use the prefixes ortho-, meta-, and para- to show where a substituent is placed on the ring. Many of these compounds also have trivial, or common, names. For systematic naming, the ring is numbered from the carbon...

structure of amines

Amines: Shape, Bonding, and Chirality

Amines have a nitrogen atom with a lone pair of electrons. That lone pair affects the shape of the molecule, the bond angles, and the bond lengths around nitrogen. In most amines, nitrogen is hybridized and attached to three substituents. The bond angle is about 108°, which is a little less than the 109.5° tetrahedral angle. The C–N–H bond angle is slightly larger at 112°, and the carbon-nitrogen bond length is 147 pm. This bond is longer than the carbon-oxygen bond in alcohols, which is 143...

physical properties of amines

Amines: Smell, Solubility, and Boiling Points

Amines show clear physical properties that depend on molecular size and structure. Low molecular weight amines are usually gases at room temperature, while higher molecular weight amines are often liquids or solids. Many low molecular weight amines also have a rotten fish-like smell, and diamines usually have a pungent odor. Amines are polar molecules, so they can take part in intermolecular hydrogen bonding. Primary and secondary amines have N–H bonds that allow these interactions. Because of...

basicity of aliphatic amines

How Aliphatic Amines Act as Bases

Aliphatic amines act as bases because the nitrogen atom can accept a proton from an acid. They can also behave as Lewis bases, since the nitrogen lone pair can form a covalent bond with an electrophile. These properties make amines useful examples of basic behavior in organic chemistry. Amine basicity is commonly described in two ways. One method uses the basicity constant, K b, for the reaction in which the amine removes a proton from water. A lower K b means a stronger base. By this measure,...

basicity of aromatic amines

Why Aromatic Amines Are Less Basic

Aromatic amines are less basic than aliphatic amines because the nitrogen lone pair can share electrons with the aryl ring through resonance. When the lone pair is delocalized, it is less available to accept a proton, so the amine shows weaker basicity. Substituents on the aryl ring can change this effect. Electron-donating groups increase electron density on the ring and raise the basicity of the amine. Electron-withdrawing groups have the opposite effect and can lower basicity sharply. A...

basicity of heterocyclic aromatic amines

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...

nmr spectroscopy of amines

Amines in NMR: Key Signal Patterns

Amines in NMR spectroscopy show clear signal patterns that help identify their structure. In proton NMR, primary amines and secondary amines give a broad N–H signal between δ 0.5 and 5 ppm. The exact position can change with sample concentration, hydrogen bonding, and the solvent used. The N–H protons in amines are labile, which means they exchange quickly in solution. Because of this fast proton exchange, they do not split with nearby protons. Their peak stays broad and does not reveal the...

mass spectrometry of amines

Amines in Mass Spectra

Amines in mass spectra show a clear pattern that helps identify them. Their parent ions often have odd molecular weights, which follows the nitrogen rule. That rule says a molecule with an odd number of nitrogen atoms gives a molecular ion with an odd molecular weight. Amines also break apart in a characteristic way during alpha cleavage. Alpha cleavage means the bond next to the nitrogen atom splits. This forms nitrogen-containing cations called iminium ions and alkyl radicals. The molecular...

preparation of amines: alkylation of ammonia and amines

preparation-of-amines-alkylation-of-ammonia-and-amines

Alkylation of Ammonia to Make Amines

To make only primary amines, chemists use specific reaction conditions such as excess ammonia. Ammonia is the most common substrate because it is cheap and readily available. Tertiary alkyl halides are not the best choice for alkylation because they are too hindered. Secondary alkyl halides can react, but they are also less preferred because they tend to undergo elimination reactions.

preparation of 1&deg; amines: azide synthesis

Azide Route to Primary Amines

Azide synthesis is a useful route to primary amines. It helps avoid the polyalkylation that can happen when ammonia is alkylated directly. In that direct reaction, unwanted polyalkylated amines and a quaternary ammonium salt can form. In the azide method, azide ions act as strong nucleophiles. A nucleophile is a species that donates an electron pair in a reaction. They react with unhindered alkyl halides to make alkyl azides. Alkyl azides do not take part in more nucleophilic substitution...

preparation of 1&deg; amines: gabriel synthesis

preparation-of-1-amines-gabriel-synthesis

Gabriel Synthesis for Primary Amines

Gabriel synthesis is a selective way to make primary amines. It avoids direct alkylation, which can create polyalkylated products. For that reason, it is a preferred method when the goal is to make only one alkylated amine product. The reaction starts with phthalimide, which holds nitrogen in a protected form. A strong base such as NaOH or KOH removes a hydrogen from phthalimide and forms an anion. This anion acts as a nucleophile and attacks an alkyl halide, giving N-alkylphthalimide. The...

preparation of amines: reduction of oximes and nitro compounds

preparation-of-amines-reduction-of-oximes-and-nitro-compounds

Routes to Amines from Oximes and Nitro Groups

Oximes and nitro compounds can both be converted into primary amines. Oximes are reduced by catalytic hydrogenation, hydride reduction, or sodium metal reduction. A primary amine is an amine with one carbon group attached to nitrogen, so this step is an important way to build nitrogen-containing molecules. Nitro compounds follow a similar path to primary amines. Aliphatic and aromatic nitro compounds can be reduced by catalytic hydrogenation or by active metals such as Fe, Zn, and Sn in the...

preparation of amines: reduction of amides and nitriles

preparation-of-amines-reduction-of-amides-and-nitriles

Making Amines from Nitriles and Amides

Nitriles and amides can both be turned into amines by reduction. Nitriles are reduced to primary amines with reducing agents such as lithium aluminum hydride or by catalytic hydrogenation. In this reaction, the amino group is added with one extra carbon in the chain. Nitriles are often made first from alkyl halides and sodium cyanide. This step follows an S N 2 mechanism, and primary alkyl halides are the best substrates for preparing nitriles. The nitrile can then be reduced to the primary...

preparation of amines: reductive amination of aldehydes and ketones

preparation-of-amines-reductive-amination-of-aldehydes-and-ketones

Making Amines with Reductive Amination

Reductive amination is a way to make amines from carbonyl compounds and primary amines. A carbonyl compound is a molecule with a carbon-oxygen double bond. The reaction first forms an imine, and then the same mixture is reduced to give a secondary amine. Selective reducing agents make this step work. Sodium cyanoborohydride and sodium triacetoxyborohydride are commonly used because they reduce the imine without reacting too aggressively. Reductive amination with sodium cyanoborohydride is...

preparation of 1&deg; amines: hofmann and curtius rearrangement overview

preparation-of-1-amines-hofmann-and-curtius-rearrangement-overview

Carbon-Loss Routes to Primary Amines

Carbon-loss reactions can turn certain amides into primary amines. The Hofmann rearrangement uses an aqueous base and a halogen to remove the carbonyl group as carbon dioxide and form a primary amine. It often gives aryl and alkyl primary amines in high yield, and the products are free of secondary and tertiary amine contamination. The Curtius rearrangement follows a similar goal but starts from an acyl azide. When heated, the acyl azide converts into a primary amine and releases nitrogen gas...

preparation of 1&deg; amines: hofmann and curtius rearrangement mechanism

preparation-of-1-amines-hofmann-and-curtius-rearrangement-mechanism

Primary Amine Synthesis by Rearrangement

Hofmann and Curtius rearrangements are used to make primary amines from carboxylic acid derivatives. In the Hofmann rearrangement, a primary amide is treated with a base and then halogenated to form an N-haloamide. A second proton loss gives a stable anionic species that rearranges to an isocyanate after an alkyl group migrates from the carbonyl carbon to the nearby nitrogen. The isocyanate then reacts with water to form carbamic acid. Carbamic acid breaks down on its own to release carbon...

amines to amides: acylation of amines

Using Acylation to Modify Amines

Amines can be modified by acylation to form amides. In this reaction, a carboxylic acid derivative such as an acid chloride, ester, or anhydride provides the acyl group. The process uses two equivalents of amine, and each one has a different job. The first amine acts as a nucleophile. It attacks the carbonyl carbon and forms a tetrahedral intermediate. The leaving group then leaves, and the C=O bond is restored. The second amine acts as a Brønsted base, meaning it removes a proton from the...

amines to alkenes: hofmann elimination

Hofmann Elimination and Alkene Formation

Hofmann elimination turns an amine into an alkene through an E2 elimination. The amine is first changed into a good leaving group. A quaternary ammonium salt is formed by treating the amine with an excess of alkyl halide, which gives a halide salt. Next, the halide salt is converted into a hydroxide salt. This hydroxide salt acts as a base during the elimination. With heat, the hydroxide removes a proton from the beta carbon. At the same time, an alkene forms and a neutral amine molecule...

amines to alkenes: cope elimination

Syn Elimination in Cope Reaction

The Cope elimination reaction converts tertiary amines into alkenes. It uses hydrogen peroxide and heat. The process starts with oxidation of the tertiary amine to form an amine oxide. The amine oxide then acts as a base during the elimination step. The reaction follows syn stereochemistry, which means the groups leave from the same side. It also proceeds through a cyclic transition state. The N,N-dimethyl hydroxylamine group is formed as the leaving group. The major product is usually the...

1&deg; amines to diazonium or aryldiazonium salts: diazotization with nano2 overview

1-amines-to-diazonium-or-aryldiazonium-salts-diazotization-with-nano2

Nitrous Acid Reactions with Amines

Nitrous acid reacts with amines in acidic conditions, and the products depend on the type of amine. It is a key nitrogen-containing acid, but it is weaker than nitric acid. Nitrous acid has a pKa of 3.37, so it ionizes in water to form nitrite ion and hydronium ion. Nitrous acid is unstable, so it is made in situ, or formed in the reaction mixture as needed. A sodium nitrite solution is combined with a cold aqueous acid such as hydrochloric acid or sulfuric acid. In acid, the –OH group of...

1&deg; amines to diazonium or aryldiazonium salts: diazotization with nano2 mechanism

Diazotizing Primary Amines with Nitrous Acid

Diazotizing primary amines with nitrous acid forms diazonium salts. The reaction begins with nitrous acid, a weak and unstable acid made in situ from sodium nitrite and cold, dilute hydrochloric acid. In acidic solution, nitrous acid is protonated and loses water to form the nitrosonium ion, which acts as the electrophile. Primary amines react with the nitrosonium ion to start diazotization. The amine serves as the nucleophile and attacks the electrophile. After deprotonation, an N-nitrosamine...

2&deg; amines to n-nitrosamines: reaction with nano2

2-amines-to-n-nitrosamines-reaction-with-nano2

Nitrosamine Formation from Secondary Amines

Secondary amines can form N-nitrosamines when they react with nitrous acid. Nitrous acid is weak and unstable, so it is made in the reaction mixture from sodium nitrite and a strong acid such as hydrochloric acid or sulfuric acid. The reaction is carried out in cold conditions. In acid, nitrous acid becomes protonated. It then loses water and forms the nitrosonium ion, a reactive electrophile. The secondary amine acts as a nucleophile and attacks this ion. That step gives an N-nitrosammonium...

diazonium group substitution with halogens and cyanide: sandmeyer and schiemann reactions

diazonium-group-substitution-with-halogens-cyanide-sandmeyer

Making Aryl Halides from Diazonium Salts

Arenediazonium salts can be used to make substituted aromatic compounds. In these reactions, the diazonium group is replaced by other functional groups such as halides, hydroxyl, and nitrile. The transcript focuses on how this chemistry is used to form aryl chlorides, bromides, fluorides, iodides, and nitriles. When arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide, they form the corresponding aryl chloride, aryl bromide, or aryl nitrile. These are called...

diazonium group substitution: &ndash;oh and &ndash;h

Arenediazonium Salt Reactions: Phenols and H

Arenediazonium salt reactions show how a diazonium group can be replaced by other functional groups. These reactions begin with diazotization, the formation of an arenediazonium salt from a primary arylamine. The process uses nitrous acid, which is made in situ from sodium nitrite and a strong acid under cold conditions. In acidic solution, nitrous acid breaks down to form nitrosonium ions. A primary arylamine then attacks the nitrosonium ion. This first step leads to an N-nitrosoaminium ion...

aryldiazonium salts to azo dyes: diazo coupling

aryldiazonium-salts-to-azo-dyes-diazo-coupling

Diazo Coupling and Azo Dye Formation

Diazo coupling is the reaction that forms azo dyes from aryldiazonium salts and highly activated aromatic compounds. The product contains an —N=N— azo linkage, and the nitrogen atoms from the diazonium salt remain in the product. Phenols and arylamines are common activated partners for this reaction. The coupling usually takes place at the para position on the aromatic ring. If the para position is already occupied, the reaction shifts to the ortho position instead. The mechanism is an...

amines to sulfonamides: the hinsberg test

Amines and the Hinsberg Reagent Test

The Hinsberg test identifies primary, secondary, and tertiary amines by their reaction with benzenesulfonyl chloride, also called the Hinsberg reagent. It is named after Oscar Hinsberg. The test uses excess aqueous base, and the mixture is then acidified to show different results for each amine type. A primary amine reacts with the Hinsberg reagent to form an N-substituted benzenesulfonamide. The sulfonyl group pulls electron density away and makes the N-H proton acidic. Because of this, base...

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

organic chemistry

JoVE Core Organic Chemistry explains basic concepts of stereochemistry, reactions, and mechanisms using concise and easy-to-understand animated video lessons. Additionally, the scientist-in-action videos demonstrate the application of related concepts in classical and original research experiments performed in today's laboratories worldwide.

Why Ring Nitrogen Changes Amine Basicity

Description

Transcript