Amines and Amides

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Amines and Amides

• Chapter 17

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Bonding characteristics of nitrogen atoms in
organic compounds

• We saw already that carbon atoms (Group 4A) form
  four bonds to other atoms in organic compounds.
• And oxygen atoms (Group 6A) form two bonds.
• Nitrogen atoms (Group 5A) require three bonds to
  give them octets. Normally, nitrogen atoms are
  involved in three covalent bonds to other atoms.

The important arrangement for this chapter
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Structure and classification of amines

• Amines are organic derivatives of ammonia (NH3),
  in which one or more alkyl, cycloalkyl, or
  aromatic groups replace hydrogen and bond to the
  nitrogen atom.

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Structure and classification of amines

• Amines are classified as primary, secondary, and
  tertiary, as we have seen previously for
  alcohols.
• For alcohols, the type of carbon atom (1o, 2o,
  3o) bound to the OH group determined whether the
  alcohol was primary, secondary, or tertiary.
• For amines, it is the number of carbon groups
  that are bound to the nitrogen atom.

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Structure and classification of amines

• This is an important difference in the way that
  1o, 2o, and 3o classification is given.
• The NH2 group of a primary amine can be thought
  of as an amino group. Thus secondary and
  tertiary amines possess substituted amino groups.

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Structure and classification of amines
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Nomenclature for amines

• Common and IUPAC systems are used extensively for
  naming amines.
• In the common system, rules similar to what we
  have seen for ethers are employed, naming the
  alkyl/aromatic groups attached to the functional
  group, and then following these with amine

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Nomenclature for amines

• The IUPAC system for naming amines is as follows
• Select the longest carbon chain bound to the
  nitrogen as the parent chain
• Name the chain by changing the alkane name for
  this chain drop the e and add amine
• Number the chain to give the nitrogen the lowest
  numbering
• The number and identity of other substituents
  (including any on the main chain) are indicated
  at the beginning of the amine name (some are
  attached to N)

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Structure and classification of amines

• Some examples. First, 1o amines

4-C chain (butane - e amine)
to indicate placement of NH2 group
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Structure and classification of amines

• For di- and trisubstituted amines, the non-parent
  chains are indicated as N-bonded

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Structure and classification of amines

• For diamines, the molecule is named as an
  alkane-diamine with NH2 groups numbered.
• And for cases where NH2-substituted alcohols or
  other compound cases are involved, the NH2-group
  is called an amino substituent.

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Structure and classification of amines

• In cases where substituted parent chains are
  encountered, the substituents are named at the
  beginning of the compounds name

Parent chain pentane Amino-position C-2 of
parent chain CH3- substituents on parent chain
(C-4) and N
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Structure and classification of amines

• Aromatic amines involve an amine-type nitrogen
  bound to an aromatic ring. The simplest case for
  these is aniline.

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Structure and classification of amines

• For substituted anilines, the substituent names
  are treated in a manner similar to what was shown
  for substituted parent chain cases

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Isomerism for amines

• Skeletal and positional isomers for amines are
  possible.
• In skeletal isomers, the carbon chain components
  of the amines differ

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Isomerism for amines

• Positional isomers differ in the placement of the
  NH2 group along the parent chain.
• Positional isomers are possible for substituted
  amines as well

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Physical properties of amines

• Amines tend to be gases for low molecular weight
  cases (e.g. up to (CH3)3N, trimethylamine) and
  many heavier ones are liquids at room
  temperature.
• One very noticeable thing about amines is that
  they tend to exhibit strong odors. For example,
  some have a fishy smell

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Physical properties of amines

• Amine boiling points are intermediate of those
  for alcohols and alkanes of similar molar mass.
• Because of the presence of N-H bond(s) in primary
  and secondary amines, hydrogen-bonding is
  sometimes possible however, because N is not as
  electronegative as O, the N-H bond is not as
  polar as an O-H bond (weaker H-bonding).

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Physical properties of amines

• Amines tend to be water-soluble because of
  H-bonding interactions with water molecules. In
  fact, amines having fewer than six carbon atoms
  are infinitely water-soluble.
• Water-solubility decreases as
• Chain length increases, and,
• The degree of N-substitution increases

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Basicity of amines

• Ammonia is one of the few examples of a weak base
  we looked at in the first semester. It reacts
  with water molecules to produce OH- ions, making
  the resulting solution basic
• NH3 H2O D NH4 OH-
• The resulting ion (NH4) is called an ammonium
  ion.
• Amines react with water to produce ammonium-like
  species.
• CH3NH2 H2O D CH3NH3 OH-

ammonium ion
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Basicity of amines

• A substituted ammonium ion results from the
  reaction between an amine and water.

substituted ammonium ion
Nitrogen tends to bond to three other atoms to
get an octet when it forms four bonds (in an
ammonium salt), the nitrogen structure carries a
positive charge
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Basicity of amines

• Naming substituted ammonium ions
• Named similar to amine, but with the term
  ammonium ion instead of amine

Methylammonium ion
Methylamine
Others
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Basicity of amines

• Amines are better bases than oxygen-containing
  compounds.
• A comparison
• Ethers and alcohols have no significant basicity
  in water

A carboxylate ion
(from ethanoic acid)
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Amine salts

• Amines, because they are basic, can react with
  acids in neutralization reactions. The reaction
  produces an amine salt, as follows
• R-NH2 H-Cl D R-NH3Cl-

amine
amine salt
Naming named as an ammonium chloride
Example (CH3)3NCl- is Trimethylammonium chloride
Amine salts are ionic compounds in which the
positive ion comes from the substituted ammonium
and the negative ion comes from an acid used to
react with the parent amine.
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Amine salts

• Amine salts are water-soluble many amines
  (having higher molar masses) are not. Thus, in
  order to introduce an amine-based drug into he
  body, it is often converted into the salt form.
• Many pharmaceuticals possess nitrogen centers
  that are protonated to the ammonium form, to make
  them water-soluble, or to stabilize them (they
  are often called hydrochlorides).

Paxil
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Amine salts

• The neutral form of an amine drug is often called
  its free-base form. In this neutral form, the
  drug may be vaporized (because the intermolecular
  forces that keep it in a condensed state at room
  temperature can be overcome by heating).
• The ionic form has a very high boiling point and
  usually cannot be vaporized without decomposing
  the structure.

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Preparation of amines and quaternary ammonium
salts

• Preparation of amines from ammonia is possible
  under basic conditions
• NH3 alkyl halide ? 1o amine
• 1o amine alkyl halide ? 2o amine
• 2o amine alkyl halide ? 3o amine
• 3o amine alkyl halide ? quaternary ammonium
  salt

base
base
base
base
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Preparation of amines and quaternary ammonium
salts

• When ammonia or an amine is treated with an alkyl
  halide in the presence of a strong base, the
  following reaction occurs

alkyl halide
ammonia
substituted amine
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Preparation of amines and quaternary ammonium
salts

• When this reaction is being carried out, it is
  necessary to remove the amine as it is formed
  before a following alkylation step occurs

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Heterocyclic amines

• Heterocylic compounds involve ring structures
  that possess non-carbon atoms. We saw some
  examples in earlier chapters (cyclic ethers,
  cyclic esters, etc.)
• Nitrogen heterocycles are frequently encountered
  in biochemistry. Some examples are

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Heterocyclic amines

• The following nitrogen heterocycles are found
  frequently in biologically relevant structures.
  For example, the purine structure is present in
  caffeine (drug), adenine and guanine (DNA).

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Heterocyclic amines

• The nitrogen heterocycle shown below is used for
  oxygen transport in the body. The heme structure
  (right) is present in the bloodstream as a
  component of a much bigger molecule (hemoglobin)
  and acquires/releases O2.

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Selected biologically important amines

• Neurotransmitters substances that are released
  at the end of a nerve which travel across the
  synaptic gap to another nerve and trigger a nerve
  impulse by binding to a chemical receptor site.

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Selected biologically important amines
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Selected biologically important amines

• Epinepherine (adrenaline) a central nervous
  system stimulant. Its release causes blood
  glucose levels to rise, blood pressure to
  increase, increased heart rate and muscle
  strength.

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Selected biologically important amines

• Histamine responsible for the symptoms
  experienced during hay fever. The body stores
  histamines, which are released in the presence of
  pollen/dust/allergens. The response is produced
  when histamines bind to receptor sites in complex
  molecules.
• Antihistamines (present in a medication) bind to
  these same receptor sites, and block the
  histamine response.

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Alkaloids

• There are some very important nitrogen-containing
  plant extracts (alkaloids) that are used in
  medicinal science (all of which are amines)

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Structure and classification of amides

• Amides possess a functional group that consists
  of a CO (carbonyl) directly bound to a nitrogen
• The amide functional group involves a nitrogen
  atom (and lone pair), but unlike an amine, the
  nitrogen center is not basic, due to the
  electron-withdrawing effect of the CO group.

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Structure and classification of amides

• Amides may be primary, secondary, or teritary

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Structure and classification of amides

• In terms of their structure, amines may be
  aromatic (benzene substituents) for example,
  benzamide
• They may also be cyclic, or even involve multiple
  amide groups in a single ring

A d-lactam
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Structure and classification of amides

• In Ch-16, we looked at lactones, which were
  cyclic esters
• Lactams are cyclic amides (and heterocycles)

Lactams
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Nomenclature of amides

• IUPAC system for naming amides
• Like esters, amides are made using carboxylic
  acids. The portion that comes from the
  carboxylic acid is named as a carboxylic acid
  first, before dropping the -oic acid from the
  name and adding -amide
• Substituents attached to the nitrogen are
  prefixed with N- to indicate their position
  other substituents on the parent chain are named
  as part of the parent chain (unlike for amines)

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Nomenclature of amides

• Some examples
• For aromatic cases

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Selected amides and their uses

• Urea is one of the simplest amides, formed by
  reaction between CO2 and ammonia in a series of
  metabolic reactions.
• Acetominophen is an aromatic amide
• Barbiturates derive from barbituric acid
  (sedatives/tranquilizers) are cyclic amides, made
  from urea and malonic acid

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Physical properties of amides

• Amides do not have a basic non-bonding pair of
  electrons, like amines (as mentioned)
• The simplest amides (methanamide, N-methyl, and
  N,N-dimethyl derivatives) are liquids at room
  temperature, and all unbranched amides having 2
  or more carbons on their C-chain side are solids.
• The secondary and teritary amides have lower
  melting points, with tertiary amides having lower
  melting points than secondary amides (less
  opportunity for H-bonding).

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Physical properties of amides
4 locations on a primary amide group that may
participate in intermolecular H-bonding
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Preparation of amides

• Amides are prepared in a manner similar to what
  weve already seen for esters. A condensation
  reaction involving a carboxylic acid is needed,
  this time with an amine

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Preparation of amides

• For amide formation to happen, the temperature
  must be high (at room temperature, an acid-base
  neutralization reaction happens instead).
• Also, the amine used in the reaction must be
  either a primary or secondary amine (cant be a
  tertiary amine).

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Preparation of amides

• Ammonia carboxylic acid ? 1o amide
• 1o amine carboxylic acid ? 2o amide
• 2o amine carboxylic acid ? 3o amide

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Preparation of amides

• Reactions that make esters from carboxylic acids
  and alcohols are called esterification reactions.
• Reactions that make amides from carboxylic acids
  and amines (or ammonia) are called amidification
  reactions. Thus amidification reactions are
  condensation reactions.
• In the condensation, the carboxylic acid loses
  the OH and the amine loses a H atom

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Hydrolysis of amides

• Like esters, amides can undergo hydrolysis. This
  reaction results in the amide being broken up
  into amine and carboxylic acid starting
  materials

 
 
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Hydrolysis of amides

• The products of the hydrolysis reaction will
  depend on the acidity/basicity of the reaction
  conditions.

acidic/basic conditions used
Remember what an acid does donates protons (H
ions) bases accept protons. Acids react with
bases, not with other acids.
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Hydrolysis of amides

• Under basic conditions, the carboxylic acid is
  produced as an carboxylic acid salt

Remember, carboxylic acids are acids
amines are bases
Amide hydrolysis carried out under
basic conditions is called amide saponification.
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Hydrolysis of amides

• Overall, the reaction would look like this
• Example

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Hydrolysis of amides

• Under acidic conditions, the amine is produced as
  an ammonium salt

Remember, carboxylic acids are acids
amines are bases
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Hydrolysis of amides

• Overall, under acidic conditions, the reaction
  would look like this
• Example

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Polyamides

• Like we saw for esters, amide condensation
  reactions can be used to make polymers (another
  polycondensation reaction).
• As for polyesters, di-functional reactants are
  needed for polymerization (i.e. a diamine and a
  dicarboxylic acid)

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Polyamides

• Nylon-6,6 is a polyamide. It can be synthesized
  from Hexanedioic acid and 1,6-Hexanediamine

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Polyamides

• Kevlar (bullet-proof
• vests) is also a
• polyamide