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
Organic Chemistry, UNAM School of Medicine
TerminologyTerminologyTerminologyTerminology
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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
Organic Chemistry, UNAM School of Medicine
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TerminologyTerminologyTerminologyTerminology
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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
Organic Chemistry, UNAM School of Medicine
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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Importance??Importance??Importance??Importance??
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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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Importance??Importance??Importance??Importance??
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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
Organic Chemistry, UNAM School of Medicine
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Structure of carboxylic acids Structure of carboxylic acids Structure of carboxylic acids Structure of carboxylic acids
& derivatives& derivatives& derivatives& derivatives
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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
Organic Chemistry, UNAM School of Medicine
Structure of carboxylic acids Structure of carboxylic acids Structure of carboxylic acids Structure of carboxylic acids
& derivatives& derivatives& derivatives& derivatives
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Structure + bonding of carboxylic acids Structure + bonding of carboxylic acids Structure + bonding of carboxylic acids Structure + bonding of carboxylic acids
& derivatives& derivatives& derivatives& derivatives
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� The two most important structural features of the carbonylgroup are:
Organic Chemistry, UNAM School of Medicine
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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Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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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
Organic Chemistry, UNAM School of Medicine
C
Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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� Examples:
Organic Chemistry, UNAM School of Medicine
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Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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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.
Organic Chemistry, UNAM School of Medicine
C
Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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� Examples:
Organic Chemistry, UNAM School of Medicine
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Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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� Systematic names (IUPAC) …cont’d
- Cyclic carboxylic acids: Add “carboxylic acid-” to the name of the
cyclic compound
� Examples:
Organic Chemistry, UNAM School of Medicine
Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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� Systematic names (IUPAC) …cont’d
- Aromatic acids: Named as derivatives of benzoic acid
� Examples:
Organic Chemistry, UNAM School of Medicine
benzoic acid p-aminobenzoic acid(4-aminobenzoic acid)
o-hydroxybenzoic acid(2-hydroxybenzoic
acid)
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Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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� Systematic names (IUPAC) …cont’d
- Aliphatic dicarboxylic acids: Named by adding the suffix “-dioic
acid” to the name of the parent alkane
� Examples:
Organic Chemistry, UNAM School of Medicine
Nomenclature of Nomenclature of Nomenclature of Nomenclature of carboxylic acidscarboxylic acidscarboxylic acidscarboxylic acids
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� Systematic names (IUPAC) …cont’d
- Cyclic dicarboxylic acids: Carboxyl groups are treated as
substituents on the cyclic structure
� Examples:
Organic Chemistry, UNAM School of Medicine
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EstersEstersEstersEsters
23 Organic Chemistry, UNAM School of Medicine
Importance??Importance??Importance??Importance??
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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
Organic Chemistry, UNAM School of Medicine
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:
Organic Chemistry, UNAM School of Medicine
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Nomenclature of Nomenclature of Nomenclature of Nomenclature of estersestersestersesters
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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:
Organic Chemistry, UNAM School of Medicine
Nomenclature of Nomenclature of Nomenclature of Nomenclature of estersestersestersesters
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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:
Organic Chemistry, UNAM School of Medicine
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Nomenclature of Nomenclature of Nomenclature of Nomenclature of estersestersestersesters
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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:
Organic Chemistry, UNAM School of Medicine
AmidesAmidesAmidesAmides
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Importance??Importance??Importance??Importance??
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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
Organic Chemistry, UNAM School of Medicine
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
Organic Chemistry, UNAM School of Medicine
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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
Organic Chemistry, UNAM School of Medicine
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:
Organic Chemistry, UNAM School of Medicine
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Nomenclature of amidesNomenclature of amidesNomenclature of amidesNomenclature of amides
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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
Organic Chemistry, UNAM School of Medicine
Nomenclature of amidesNomenclature of amidesNomenclature of amidesNomenclature of amides
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� Examples:
Organic Chemistry, UNAM School of Medicine
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Nomenclature of amidesNomenclature of amidesNomenclature of amidesNomenclature of amides
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� Common & Systematic names (IUPAC) …cont’d
- Cyclic amides are called “lactams” in common nomenclature
- Nomenclature is similar to that of lactones
Organic Chemistry, UNAM School of Medicine
Nomenclature of amidesNomenclature of amidesNomenclature of amidesNomenclature of amides
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� Common & Systematic names (IUPAC) …cont’d
- Named as “2-azacycloalkanones” in systematic nomenclature
- “aza” = Used to designate the N atom
� Examples:
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Acyl HalidesAcyl HalidesAcyl HalidesAcyl Halides
39 Organic Chemistry, UNAM School of Medicine
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
5/2/2012
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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:
Organic Chemistry, UNAM School of Medicine
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
Organic Chemistry, UNAM School of Medicine
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Reactivity of Reactivity of Reactivity of Reactivity of acyl halidesacyl halidesacyl halidesacyl halides
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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
Reactivity of Reactivity of Reactivity of Reactivity of acyl halidesacyl halidesacyl halidesacyl halides
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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:
Organic Chemistry, UNAM School of Medicine
Some − chargednucleophiles:
Some neutralnucleophiles:
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Reactivity of Reactivity of Reactivity of Reactivity of acyl halidesacyl halidesacyl halidesacyl halides
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� Nucleophilic acyl substitution:
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Acid AnhydridesAcid AnhydridesAcid AnhydridesAcid Anhydrides
46 Organic Chemistry, UNAM School of Medicine
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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
Organic Chemistry, UNAM School of Medicine
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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:
Organic Chemistry, UNAM School of Medicine
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
51 Organic Chemistry, UNAM School of Medicine
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
Organic Chemistry, UNAM School of Medicine
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:
Organic Chemistry, UNAM School of Medicine
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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:
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Thank you
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END
Organic Chemistry, UNAM School of Medicine