(21) session 21 carboxylic acids & carboxylic acid derivatives i

5/2/2012

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Session 21

Organic Chemistry, UNAM School of Medicine1

Carboxylic Acids & Carboxylic Acids & Carboxylic Acids & Carboxylic Acids &

Carboxylic Acid Derivatives ICarboxylic Acid Derivatives ICarboxylic Acid Derivatives ICarboxylic Acid Derivatives I

Dr L.H.A. Prins (Ph.D.)

Dept. of Pharmacy

UNAM

Learning Outcomes

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� By the end of this session, the student should be able to:

�Understand what a carbonyl group, acyl group &

carbonyl compound is

�Understand the importance of carboxylic acids & its

derivatives

�Describe the structure of carboxylic acids & its derivatives

�Name carboxylic acids & its derivatives according to IUPAC

system

Organic Chemistry, UNAM School of Medicine

Carbonyl Compounds I

Carbonyl Compounds I

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TerminologyTerminologyTerminologyTerminology

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� Carbonyl group – a C double

bonded to an O

� Carbonyl compound – compound

containing a carbonyl group

� Acyl group – carbonyl group

attached to an alkyl group or to an

aryl group



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� Carbonyl compounds:Divided into 2 classes

� Class I carbonyl compounds = acyl group is attached to an atom or a group that can be replaced by another group


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� Carbonyl compounds:Divided into 2 classes

� Class II carbonyl compounds = acyl group is attached to agroup that can not be readily replaced by another group


Carboxylic AcidsCarboxylic AcidsCarboxylic AcidsCarboxylic Acids

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Importance??Importance??Importance??Importance??

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� Carboxylic acids – found widely throughout nature� (S)-(+)-Lactic acid: Responsible

for the burning sensation felt in

muscles during anaerobic exercise

� Oxalic acid: Contained in spinach

& other leafy green vegetables



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� Carboxylic acids – found widely throughout nature� Succinic acid & citric acid: Important intermediates in the

citric acid cycle

� Prostaglandins: Hormones that stimulate inflammation, cause hypertension & produce pain

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� Carboxylic acids – found widely throughout nature� p-Aminobenzoic acid: Used in

sunscreens; absorbs

short-wavelength UV light

� Gamma-aminobutanoic acid (GABA):

A prominant inhibitory neurotransmitter

Structure of carboxylic acids Structure of carboxylic acids Structure of carboxylic acids Structure of carboxylic acids

& derivatives& derivatives& derivatives& derivatives

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� Functional group of carboxylic acids consists of a C=O with -OH bonded to the same C

� Carboxyl group is usually written -COOH

� Aliphatic acids - alkyl group bonded to -COOH

� Aromatic acids - aryl group bonded to -COOH


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� Carbonyl carbon in carboxylic acids & carboxylic acid derivatives is sp2 hybridised

� Uses its 3 x sp2 orbitals to form σ bonds to the carbonyl O, the α-C &

a substituent (R)

� 3 atoms attached to carbonyl C are in the same plane & their bond

angles are each approximately 120°� Carbonyl oxygen is also sp2 hybridised

� 1 of its sp2 orbitals forms a σ bond with the carbonyl C & each of the

other 2 sp2 orbitals contains a lone pair e-

� Remaining p orbital of carbonyl O overlaps with remaining p orbital

of carbonyl C to form a π bond





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Structure + bonding of carboxylic acids Structure + bonding of carboxylic acids Structure + bonding of carboxylic acids Structure + bonding of carboxylic acids


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� The two most important structural features of the carbonylgroup are:


Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids

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� Common names - carboxylic acids having 6 or fewer C are frequently called by their common names. These names were chosen by early chemists to describe some feature of the compound, usually its origin

� Examples:


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� Common names - position of a substituent is designated by a lowercase Greek letter & the carbonyl C is not given a designation. C adjacent to carbonyl C is the α-C, C adjacent to α-C is the β-C& so on


C


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� Examples:


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� Systematic names (IUPAC) - named by replacing the terminal “e”of the alkane name with “oic acid” Position of a substituent is designated by a #.

Carbonyl C of a carboxylic acid is always carbon # 1.


C


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� Examples:


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� Systematic names (IUPAC) …cont’d

- Cyclic carboxylic acids: Add “carboxylic acid-” to the name of the

cyclic compound

� Examples:



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- Aromatic acids: Named as derivatives of benzoic acid

� Examples:


benzoic acid p-aminobenzoic acid(4-aminobenzoic acid)

o-hydroxybenzoic acid(2-hydroxybenzoic

acid)

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- Aliphatic dicarboxylic acids: Named by adding the suffix “-dioic

acid” to the name of the parent alkane

� Examples:



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- Cyclic dicarboxylic acids: Carboxyl groups are treated as

substituents on the cyclic structure

� Examples:


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EstersEstersEstersEsters



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� Esters – also commonly found in nature� Many of the fragrances of flowers & fruits are due to esters


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Structure of estersStructure of estersStructure of estersStructure of esters

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� Esters (R-COOR') have an −OR' group in place of the −OH group of a carboxylic acid (R-COOH)

� Esters can be cyclic or acyclic

� Hybridisation structure: Refer to Slides 11-12


Nomenclature of Nomenclature of Nomenclature of Nomenclature of estersestersestersesters

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� Common names - name of the group (R') attached to the

carboxyl oxygen (from an alcohol) is stated first, followed by the

name of the acid, with “ic acid” replaced by “ate”

� Examples:


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� Common names - cyclic esters are called lactones. Derived from

the common name of the carboxylic acid, which designates the length

of the carbon chain, & a Greek letter to indicate the C to which the

carboxyl oxygen is attached

� β-lactones = 4-membered ring lactones

� γ-lactones = 5-membered ring lactones

� δ-lactones = 6-membered ring lactones

� Examples:



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� Systematic names (IUPAC) - named by naming the R’ group (from an alcohol) as an alkyl group first followed by the acid name (the R-C group) with ending “–oate”

� Remember:

“Alkyl alkanoate”

� Examples:


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� Systematic names (IUPAC) - cyclic esters are named as“2-oxacycloalkanones”. Replace “alk”-part with amount of C’s in ring

� “oxa” = Used to designate the O atom

� Examples:


AmidesAmidesAmidesAmides


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� Amino acids are linked together by amide bonds to form peptides & proteins

� Caffeine: Naturally occurring amide

found in cocoa & coffee beans

� Penicillin G (‘normal’ penicillin):

Compound with two amide bonds


Structure of amidesStructure of amidesStructure of amidesStructure of amides

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� Amides (R-CONH2) have a −NH2, −NHR or −NR2 group in place

of the −OH group of a carboxylic acid (R-COOH)

� Amides can be cyclic or acyclic

� Hybridisation structure: Refer to Slides 11-12


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Structure of amidesStructure of amidesStructure of amidesStructure of amides

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� Amide classification:

� primary (1°) = 1 x C group bonded to amide N atom

� secondary (2°) = 2 x C groups bonded to amide N atom

� tertiary (3°) = 3 x C groups bonded to amide N atom


Nomenclature of amidesNomenclature of amidesNomenclature of amidesNomenclature of amides

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� Common & Systematic names (IUPAC) - use the acid name, replacing “oic acid” or “ic acid” with “amide.” For acids ending with “carboxylic acid,” “ylic acid” is replaced with “amide”

Entire name – written as one word!

� Examples:


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� Common & Systematic names (IUPAC) …cont’d

- For substituents bonded to the N - name of the substituent is

stated 1st followed by the name of the amide

- If there is more than 1 substituent bonded to the N, they are stated

alphabetically

- Name of each substituent bonded to N is preceded by an“N” (in

italics) indicating that the group is bonded to a N rather than to a

C



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� Examples:


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- Cyclic amides are called “lactams” in common nomenclature

- Nomenclature is similar to that of lactones



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- Named as “2-azacycloalkanones” in systematic nomenclature

- “aza” = Used to designate the N atom

� Examples:


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Acyl HalidesAcyl HalidesAcyl HalidesAcyl Halides


Structure of acyl halidesStructure of acyl halidesStructure of acyl halidesStructure of acyl halides

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� Acyl halides – not commonly found in nature, because of their high reactivity

� Acyl halides (R-COX) have a −X in place of the −OH group of a carboxylic acid (R-COOH)

� Acyl chlorides & acyl bromides - most common acyl halides

� Hybridisation structure: Refer to Slides 11-12Organic Chemistry, UNAM School of Medicine

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Nomenclature of Nomenclature of Nomenclature of Nomenclature of acyl halidesacyl halidesacyl halidesacyl halides

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� Common & Systematic names (IUPAC) - named by using the acid name & replacing “ic acid” with “yl chloride”(or “ylbromide”)

- Acids ending with “carboxylic acid” – replace “carboxylic acid”

with “carbonyl chloride” (or “bromide”)

� Examples:


Reactivity of Reactivity of Reactivity of Reactivity of acyl halidesacyl halidesacyl halidesacyl halides

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� Acyl halides = activated derivatives of carboxylic acids� Halogen atom (X) of an acyl halide inductively withdraws e- density

from carbonyl C, enhancing its electrophilic nature

� This makes acyl halides particularly reactive toward nucleophilicacyl substitution

� Halide ion - serves as a good leaving group


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� Electrophile = “electron-lover”= reagent/atom attracted to electrons= accepts an electron pair from a nucleophile = By definition: Lewis acids= + charged species such as H+, NH4

+or atom that carries a partial positive charge

� Nucleophile = “nucleus-lover”= donates an electron pair to an electrophile to

form a chemical bond= By definition: Lewis bases

= Molecules or ions with a free pair of electronsOrganic Chemistry, UNAM School of Medicine


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� Nucleophile = can be either − charged (:Nu-) or neutral (:Nu)= if neutral: Usually carries a H atom that can

subsequently be eliminated (:Nu-H)

� Examples:


Some − chargednucleophiles:

Some neutralnucleophiles:

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� Nucleophilic acyl substitution:


Acid AnhydridesAcid AnhydridesAcid AnhydridesAcid Anhydrides


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Structure of acid anhydridesStructure of acid anhydridesStructure of acid anhydridesStructure of acid anhydrides

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� Acid anhydrides – not commonly found in nature, because of their high reactivity

� Loss of H2O from 2 carboxylic acid molecules - Acid anhydride ((R-CO)2-O)

� “Anhydride” means “without water”

� Hybridisation structure: Refer to Slides 11-12Organic Chemistry, UNAM School of Medicine

Structure of acid anhydridesStructure of acid anhydridesStructure of acid anhydridesStructure of acid anhydrides

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� Types of acid anhydrides:� Symmetrical anhydride - the 2 COOH molecules forming the

acid anhydride are the same

� Mixed anhydride - the 2 COOH molecules forming the acid

anhydride are different


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Nomenclature of Nomenclature of Nomenclature of Nomenclature of acid anhydridesacid anhydridesacid anhydridesacid anhydrides

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Common & Systematic names (IUPAC)

- Symmetrical anhydrides: Named by using the acid name &

replacing “acid” with “anhydride”

- Mixed anhydrides: Named by stating the names of both acids in

alphabetical order, followed by “anhydride”

� Examples:


Reactivity of Reactivity of Reactivity of Reactivity of acid anhydridesacid anhydridesacid anhydridesacid anhydrides

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� Acid anhydrides = activated derivatives of carboxylic acids (like

acyl halides)

� However, acid anhydrides are not as reactive as acyl halides

� In acyl chloride - Cl atom activates carbonyl (C=O) group &

serves as a leaving group

� In acid anhydride - carboxylate group serves these functions


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NitrilesNitrilesNitrilesNitriles


Structure of nitrilesStructure of nitrilesStructure of nitrilesStructure of nitriles

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� Nitriles – compounds that contain a cyano (C=N) functional group

– considered carboxylic acid derivatives because, like all Class I carbonyl compounds, they react with H2O(hydrolyse) to form carboxylic acids


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Structure of nitrilesStructure of nitrilesStructure of nitrilesStructure of nitriles

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� Nitriles:– C & N of cyano group are sp hybridised– R-C-N bond angle is 180° (linear)

– Nitrile structure - similar to that of a terminal alkyne (propyne)– N atom of nitrile has lone pair e- instead of alkyne H


Nomenclature of Nomenclature of Nomenclature of Nomenclature of nitrilesnitrilesnitrilesnitriles

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Common & Systematic names (IUPAC)

- Common names:The suffix “-ic acid” is replaced by the suffix

“-onitrile”

- Systematic names: Constructed from the alkane name, with the

suffix “-nitrile” added

� Examples:


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Nomenclature of Nomenclature of Nomenclature of Nomenclature of nitrilesnitrilesnitrilesnitriles

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Common & Systematic names (IUPAC) …cont’d

- Substituent nomenclature: If it is seen as a substituent in a

molecule, it is called “cyano”

� Example:


Thank you

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END


(21) session 21 carboxylic acids & carboxylic acid derivatives i

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