J McM OC Pharmacy Fm 1 06

8/7/2019 J McM OC Pharmacy Fm 1 06

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O r g a n i c C h e m i s t r yO r g a n i c C h e m i s t r y

Dr.Dr. DikdikDikdik KurniaKurnia,, M.ScM.Sc

Carboxylic Acids and Their DerivativesCarboxylic Acids and Their Derivatives

LaboratoriumLaboratorium KimiaKimia OrganikOrganik JurusanJurusan KimiaKimia

FakultasFakultas MatematikanMatematikan dandan IlmuIlmu PengetahuanPengetahuan AlamAlam

UniversitasUniversitas PadjadjaranPadjadjaran

20092009


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Carboxylic Acids and Their Derivatives

1. What are the general properties of carboxylic acids and their derivatives?Be able to describe and compare such properties as hydrogen bonding,water solubility, boiling point, and acicidity or basicity.

2. How are carbocylc acid, anhydrides, esters, and amides named?Be able to name t he simple members of these families and write therstructures, given the names.

3. What are some of the significant applications and occurences of carbocylic

, , ,Be able to identify major applications and occurrences of each family ofcompoundsand describe some important members of each family.

4. How are esters and amide synthesized from carboxylic acids and convertedback to carboxylic acids?Be able to describe and predict the products of the ester- and amide-forming reactions of carbocylic acids and the hydrolysis of esters andamides.

5. What are phosphate esters and anhydrides, and why are they important?Be able to recognize and writ e the structures of phosphate esters andanhydrides and explain why they are important in biochemistry.


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Carboxylic Acids and Their Derivatives

Carbocylic acid (RCOOH):

A com ound that ha a carbon l rou bonded to on carbon substit uentand one OH group.

Acid anhydride(RCO2COR'):

A compound t hat has a carbonyl group bonded t o a carbon substit uent andan OCOR' group.

Ester (RCOOR'):

A compound t hat has a carbonyl group bonded to one carbon atom and one

ORgroup.Amide (RCONR'2):

A compound that has a carbonyl group bonded to one carbon atom andnitrogen atom group, where R' may be an H atom.


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Properties of Carboxylic Acids and Their Derivatives

Carbocylic acid, acid anhydrides, esters, and amides all have their carbonyl groups

bonded to an atom (O and N) that strongly attracts electrons.

The carbonyl groups are more strongly polarized in these families of compounds

than in ketones and aldehydes.


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The structural similarity of theses families also leads to similarities in their chemistry.

All undergo carbonyl-group substitution reactions, in which a group we can

represent as X replaces (substitutes for) OH, OCOR, OR, or NH2 group of

the starting material

Amides and esters can easily be either made from acids or converted back to acids.

Acid anhydrides are the most reactive of these carboxylic avid derivaives, and they

cannot be used in aqueous solution because of their substitution reaction withwater.


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Carbocylic acids and their derivatives all contain polar functional groups, all are

higher boiling point than comparable alkane.

Like alcohol, carbocylic acids can form hydrogen bonds witheach other.

Molecules pair off to form dimers, and even formic acid (HCOOH), the lighest and

simplest carrbocylic acid, is a liquid at room temperature with a boiling point of

101C.


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Acids with saturated straght-chain R groups contaning up to nine carbon atoms are

volatile liquids with stron, sharp odors, and those with up to four carbons are

water-soluble.

Higher saturated acids are waxy, odorless solids, and water solubility falls off as the

size of the alkane-like portion increases relative to the size of water-soluble

COOH portion.

When the OH of the carboxyl group (COOH) is converted to the OR of an ester,

the ability of the molecules to hydrogen-bond with each other is lost.

Simle esters are therefore lower boilin than the acids from which they are derived

and are also lower boiling than comparable alcohols.


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Replacement of the OH group of an acid by an NH2 group produces an

unsubstituted amide (RCONH2), that is, an amide with two hydrogen atoms on

the nitrogen atom.Such amide can form three strong hydrogen bonds to other amide molecules and are

thus higher melting and higher boiling than the acids from which they are

derived.

Note the distinction between amines and amides.

The nitrogen atom is bonded to a carbonyl-group carbon atom in an amide, but not

in an amine.

Amides are not basic like amines, mainly because the electron-withdrawing ability of

the carbonyl group causes the unshared pair of electrons on nitrogen to be held

tightly and prevents it from bonding to hydrogen.


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All undergo carbonyl-group substitution reactions

Acids anhydrides react with water to form acids Esters and amides are made from acids and easily converted back to acids

Hydrogen bonding is strong in pure acids and unsubstituted or monosubstituted

amides; none in esters.

Simpler acids and esters are liquis; all unsubstituted amides except formamide

are solids.

Acids give acidic aqueous solutions; esters and amides do not change pH.

Volatile acids have strong odors; volatile esters have pleasent, fruity odors.


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Naming of Carboxylic Acids and Their Derivatives

Carbocylic acids,

Carbocylic acids (RCOOH) are named systematically by replacing

the final eof the corresponding alkane name with oicacid. If alkyl substituents or other functional groups are present, the

chain is numbered beginning at the COOH end.

Dicarbocylic acids,

Dicarbocylic acids which contain two COOH groups are named systematically

by the ending dioic to the alkane name (the e is retained).

If alkyl substituents or other functional groups are present, the chain is

numbered beginning at the COOH end.


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Many other varieties of compounds containing COOH group are also common.

There are unsaturated acids, which are named systematically with the ending-enoic,

and there are acids containing other functional groups such as hydroxy acids and

keto acids, several of which are important biomolecules.

The carbon atoms next to the COOH group are sometimes identified by Greek

letters, beginning with .


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Acid Anhydrides,

The word anhydride means without water and acid anhydride have the

structure that results from lossof a molecule of water by two acid molecules(whether or not the anhydride is made that way).

Anhydride names are derived by replacing acid in the name of the original acid

with anhydride.


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Ester,

Ester (RCOOR') are named by first specifying the alkyl group attached to the

ether-like oxygen (OR') and then identyfing the related carbocylic acid The family name ending icacid is replaced by -ate.


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Ester names always consist of two wordsthe name of alkyl group in COOR

followed by the name of the acid with an ate ending.



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Amides (RCONH2),

Amides with an unsubstituted NH2 group are named by replacing the oic acid

of the corresponding carboxylic acid name with amide. If the nitrogen atom of the amide has alkyl substituents on it, the compound is

named by first specifying the alkyl group and then identfying the amide name.

The alkyl substituents are preceded by the letter N to identify them as being

attached directly to nitrogen.



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Some Common Carboxylic Acids

Carboxylic acids occur widely throughout the plant and animal kingdoms.

Long-chain carboxylic acids such as stearic acid are components of all animal fats

and vegetable oil, and many organic acids are formed in the body during the

beakdown of foods.


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Some Common Carboxylic Acids

Acetic acid (CH3COOH)


Long-chain carboxylic acids such as stearic acid are components of all animal fatsand vegetable oil, and many organic acids are formed in the body during the

beakdown of foods.

Citric acid (A Tricarboxylic Hydroxy Acid)


Long-chain carboxylic acids such as stearic acid are components of all animal fatsand vegetable oil, and many organic acids are formed in the body during the

beakdown of foods.


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Acidity of Carboxylic Acids

Carboxylic acids are generally weak acids and establish equilibria in aqueous

solution with carboxylate anion, RCOO-.

Many carboxylic acids have about the same acid strength as acetic acid. Carboxylate ions are named by replacing the-ic ending in the carboxylic acid name

with ate.


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Carboxylic acids react completely with strong bases such as sodiumhydroxide to

give water and a carboxylic acid salt.

Acetate ion, as the anion of a weak acid, is itself a base that can accept a proton

from HCl or some other strong acid.

Carboxylate anion can be converted back into free carboxylic acids by reaction

with acids


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The interconversion of a carboxylic acid and its carboxylate ion is easily reversible

depending on yhe conditions. Which form is present depends on the pH of the medium and can be controlled

by adjusting the pH.

At low pH (acidic solution), carboxylic acid is present; at high pH (basic solution),

carboxylation ion is present:


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Reactions of Carboxylic Acids:Ester Formation

Esterification reaction, the reaction between an alcohol and a carboxylic acid to

yield an ester plus water.

Esterification reaction is carried out by warming a carboxylic acid with an alcoholin the presence of a strong-acid catalyst such as H2SO4.

In the reaction, an H is lost from the alcohol, an OH is lost from the acid, and

water is formed as a by-product.

The net effect is substitution of OR' for OH:

Esterification reaction are reversible and often reach equilibrium with substantial

amounts of both reactans and product present.

The goodyied are obtained either by using a large excess of the alcohol or by

continuously removing one of the products (LeChateliers principle).


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Some Common Esters

Aspirin is a white, crystalline solid thats a member of the group of drugs known

as salicylates (ester of salicylic acid).

Aspirin was found to be as effective a pain reliever but with fewer unpleasant

side effects.

Methyl salicylate is a counterirritant, a substance that relieves internal pain by

stimulating nerve ending in the skin for warmth, coolness, or pain.


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Some Common Esters

Glycerol Esters is a trihydroxy alcohol that form the backbone of natural fats and

oil when it is esterified with carboxylic acids that have long hydrocarbon chain.


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Reaction of Ester: Hydrolysis Hydrolysis, the breakdown of a compound by reaction with water; the Hs and O

from water usually add to the atoms in the broken bond in one way or another.

Esters undergo a hydrolysis reaction with water splits the ester molecule into the

carbocylic acid and alcohol combined inthe ester.

The net effect of the hydrolysis is a substitution of OH for OR'.

Ester hydrolysis is catalyzed both by acids and by bases.

Acid catalyzed hydrolysis is simply the reverse of the esterification reaction.

An ester is treated with water in the presence of a strong acid such as H2SO4 and

hydrolysis takes place.


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Reaction of Ester: Saponification

Saponification reaction, the reaction of an ester with aqueous hydroxide ion to

yield an alcohol and the metal salt of a carboxylic acid.

Base-catalyzed hydrolysis take place when an ester is treated with water in thepresence of a base such as NaOH or KOH.

The main difference between the acid- and base-catalyzed hydrolysis methods is

that the base-catalyzed reaction yields the carboxylate anion as a product rather

than a free carboxylic acid.

In order to isolate the acid, the anion has to be protonated by treatment with HCl

or H2SO4.


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Reaction of Ester: Claisen Condensation

Claisen Condensation Reaction, a reaction that joins two ester molecules to yield

a keto ester product.

A claisen take a place when an ester is treated with a strong base such as sodiummethoxide, Na+OCH3-, the sodium salt of methanol.

In the reaction, the OR' group is lost from the carbpnyl group carbon of one

ester molecules, and a bond forms between that carbon and the crbon atom next

to the carbonyl group of the second molecules.

The product is a ketone-ester, or keto ester.


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Reaction of Carboxylic Acids: Amide Formation

The reaction of a carboxylic acid with ammonia or an amine yields an amide, just

as the reaction of a carboxylic acid with an alcohol yields an ester.

In both cases, water is formed as a by-product, and the OH part of the carboxylic

acid is replaced.

The reaction of a carboxylic acid with ammonia or an amine to form an amide

doesnt take place, however, unless carbonyl OH group is first replaced with a

more reactive group.

In both cases, water is formed as a by-product, and the OH part of the carboxylic

acid is replaced.

In the laboratory, a compound called DCC (dicyclohexylcarbodiimide) is oftenused.


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Although the exact way in which DCC works is a bit too complex to discuss in

detail, its function is to activate the carboxylic acid by making it much more

reactive. One activated, the carboxylic acid then reacts rapidly with an amine to generate a

amide.


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The amide bond between nitrogen and a carbonyl-group carbon is the

fundamental link in protein molecules.

Some synthetic polymers such as nylon contain amide groups, and importantpharmaceutical agent such as acetaiophen.

Glutamic acid (glutamine), one of the natural amino acids, contain an

unsubstituted amide group, and urea which carries waste nitrogen from the body

is a diamide.


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Reaction of Amide: Hydrolisis

Amide undergo a hydrolysis reaction with water in the same way that esters do.

Just as an ester yields a carboxylic aci and an alcohol when hydrolyzed, an amide

yields a carboxylic acid and an amine. The net effect of amide hydrolysis is a substitution of OH for NH 2 or the

substituted amide nitrogen.

The cleavage of amide bonds by hydrolisis is the key process that occurs in the

stomach during digestion of proteins.


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Amide hydrolisis is catalyzed both by acids and bases.

If an acid catalyst such as HCl is used, the amine product is converted into its

ammonium salt as soon as its formed. If basic catalyst such as NaOH is used, the carboxylic acid product is converted

into its carboxylate ion.

Reaction of Amide: Hydrolisis


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Acid Anhydrides

Acid anhydride contain the RC=O, or acyl group, portion of two carboxylic acids,

both bonded to a central oxygen atom.

The acyl group may be from the same or from different acid, and the anhydridegroup may form between two carboxyl groups in the same molecule.

Because acid anhydride (RCO2OCR) react rapidly with water to regenerate acids,they are not found in plants and animals.


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Acid Anhydrides

Their reactivity, however, makes anhydrides useful in the synthesis of other

carboxylic acid derivatives.

The RCO portion of an anhydride combines with an alcohol to give an ester orwith an amine to give an amide, while the remainder of the anhydride adds

hydrogen to give an acid

Aspirin, an ester in which salicylic acid provides the OH group, is synthesized by the

reaction of salicylic acid and acetic anhydride


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Phospat and Esters Anhydrides

Phosphate ester, a compound formed by reaction of an alcohol with phosphoric

acid.

Nitrate ester, a compound formed by reaction of an alcohol with nitric acid.


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Nitrate ester dont occur naturally, although nitroglycerin, a triester between

gltcerol (glycerin) and three molecules of nitric acid, is well known for its use in

the treatment of heart desease.

Phosphoric acid may be esterfied at one, two, or all three of its OH groups


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Because they still contain acidic hydrogen atoms, the monoester and diester are

also acidic.

In neutral or alkaline solutions, including body fluids that are slightly alkaline, they

are present as ions:

Phosphate esters are widespeared throughout all living organism and are key

substances in nearly all metabolic pathway.

Glyceraldehyde-3-phosphate, is one of several phosphate esters that are

intermediates in the breakdown of carbohydrate to yield energy.


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Reaction of two molecules of phosphoric acid results in loss of water and produces

a phosphorus anhydride that reseambles carboxylic acid anhydrides but unlike

them still contains four acidic hydrogen that will be ionized in solution ofappropiate pH

Reaction of this compound, known as pyrophosporic acid (sometimes called

diphosphoric acid).



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Esters of pyrophosphoric acid and triphosphoric acid are referred to as

diphosphates.

In the following two methyl phosphate esters, note the difference between thePOC ester linkage and the POP phosphorus anhydride linkage.


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Organic Reactions

Equation for organic reactions tend to appear complicated.

The bigger the molecules reacting or the longer the series of reactions, the more

intimidating the equations. Many organic reactions have the same patterns, although organic chemists tend to

call them by different names.

For example, the addition reactions of alkenes, in which water (or halogens or

hydrogen halides) add across the double bond:

Elimination reactions, such as the elimination of water to give an alkene, are

essentially the reverse of addition reactions.


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Organic Reactions


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Organic Reactions

J McM OC Pharmacy Fm 1 06

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