[Session 7] - cdn.i3l.ac.id

[Session 7]

Carboxylic acids

[PHA2103] ndash [Organic Chemistry II]

apt Nurul Fajry Maulida MLifeSc

Learning objectives

In this session the students are able to describe the properties of carboxylic acids their general synthesis and reactivity and the example of carboxylic acid drugs

Contents Carboxylic Acids

1 Naming

2 Properties

3 General Synthesis

4 Different reactions involving carboxylic acid

5 Drugs containing carboxylic acid

1 Naming

Simple carboxylic acids derived from open-chain alkanes are systematically named by replacing the terminal -e of the corresponding alkane name with -oic acid The CO2H carbon atom is numbered C1

Compounds that have a -CO2H group bonded to a ring are named using the suffix -carboxylic acid The CO2H carbon is attached to C1 in this system and is not itself numberedAs a substituent the CO2H group is called a carboxyl group

Systematic Name

The names of acylgroups R-C=O derived from the parent acids

Common Name1 Naming

2 Properties

Sp2 hybridized plannar with C-C=O and O=C-O bond angles of approximately 120o

Strong H bonding has effect on boiling points carboxylic acids boil less easily than their corresponding alcoholsAcetic acid 1170oCEthanol 783oC

Carboxylic acids with more than six carbons are only slightly soluble in water The alkali metal salts of carboxylic acids are often highly water-soluble

Carboxylic acids dissociate slightly in dilute aqueous solution to give H3O+ and carboxylate anions RCO2

-

The extent of dissociation is given by an acidity constant Ka

Carboxylic acid is much weaker than mineral acids much stronger acids than alcohols and phenols

Why are carboxylic acids so much more acidic than alcohols even though both contain OH groups

the negative charge is delocalized over two equivalent oxygen atoms

the negative charge is localized on a single electronegative atom

2 Properties

The dissociation of a carboxylic acid is an equilibrium process any factor that stabilizes the carboxylate anionrelative to undissociated carboxylic acid will drive the equilibrium toward increased dissociation and result in increased acidity

the electron-withdrawing effect of the electronegative oxygen atom

three electron-withdrawing fluorine atoms delocalize the negative charge in the trifluoroacetate anion stabilizing the ion and increasing the acidity of CF3CO2H

Substituent effects on the acidity of p-substituted Benzoic Acids

2 Properties

Electron-donating (activating) group such as methoxy decreases acidity by destabilizing the carboxylate anionElectron-withdrawing (deactivating) group such as nitro increases acidity by stabilizing the carboxylate anion

2 Properties

3 General Synthesis

Oxidation of a substituted alkylbenzene with KMnO4 or Na2Cr2O7 gives a substituted benzoic acid

Both primary and secondary alkyl groups can be oxidized but tertiary groups are not affected

Oxidation of a primary alcohol or an aldehyde yields a carboxylic acidPrimary alcohols amp aldehyde are often oxidized with CrO3 in aqueous acid

bull SN2 reaction of alkyl halides rarr Nitrilesrarr hydrolysis of nitrile

the product acid has one more carbon than the starting alkyl halide

3 General Synthesis

bull Caboxylation of Grignard Reagents

bull Reaction of a Grignard reagent with CO2 (steam of dry CO2 gas) to yield a metal carboxylate followed by protonation to give a carboxylic acid

The organomagnesium halide adds to a C=O bond of carbon dioxide

3 General Synthesis

LiAlH4




bull Ciprofloxacin is a second generationfluoroquinolonederivative antibiotics

CinoxacinSynthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections

Fluciclovine is indicated as a detection agent for positron emission tomography (PET) in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels

L-Proline is extremely important for the proper functioning of joints and tendons and also helps maintain and strengthen heart muscles

Contents Nitriles

1 Naming

2 Properties

3 General Synthesis

4 Different reactions involving nitriles

5 Drugs containing nitriles

1 Naming

bull Compounds containing the CN functional group are called nitriles and can undergo some chemistry similar to carboxylic acids

bull Simple open- chain nitriles are named by adding -nitrile as a suffix to the alkane name

bull The nitrile carbon numbered C1

bull Nitriles can also be named as derivatives of carboxylic acids by replacing the -ic acid or -oic acid ending with -onitrile or by replacing the -carboxylic acid ending with -carbonitrile

bull The nitrile carbon atom is attached to C1 but is not itself numbered

bull If another carboxylic acid derivative is present in the same molecule the prefix cyano- is used for the CN group

bull Nitriles are analogous to carboxylic acids in that both have a carbon atom with three bonds to an electronegative atom and both contain pi bond

bull Some reactions of nitriles and carboxylic acids are similar

bull Both are electrophiles and undergo nucleophilic addition reactions

2 Properties

bull Cyanocycline A has been isolated from the bacterium Streptomyceslavendulae and was found to have antimicrobial and antitumor activity

bull More than 1000 cyanogenic glycosides are derived primarily from plants cyanogenic glycosides contain a sugar with an acetal carbon one oxygen of which is bonded to a nitrile-bearing carbon (sugar -1113148 O-1113148 C-1113148 CN)

On hydrolysis with aqueous acid the acetal is cleaved generating a cyanohydrin (HO1113148 -C-1113148 CN) which releases hydrogen cyanide

2 Properties

3 General Synthesis

(a) SN2 reaction of CN- with primary or secondary alkyl halide (already discussed)

(b) Dehydration of a primary amides (RCONH2)

bull The dehydration occurs by initial reaction of SOCl2 on the nucleophilic amide oxygen atom followed by deprotonation and a subsequent E2-like elimination reaction


bull Like a carbonyl group a nitrile group is strongly polarized and has an electrophiliccarbon atom

bull Nitriles react with nucleophiles to yield sp2-hybridized imine anions in a reaction analogous to the formation of an sp3-hybridized alkoxide ion by nucleophilicaddition to a carbonyl group

bull Some general reactions


(a) Hydrolysis to yield carboxylic acids

The reaction occurs in either basic or acidic aqueous solution


bull Nucleophilic addition of hydroxide ion to the amide carbonyl group yields a tetrahedral alkoxide ion Expulsion of amide ion NH21113148 as leaving group gives the carboxylate ion thereby driving the reaction toward the products Subsequent acidification in a separate step yields the carboxylic acid


(b) Reduction to yield primary amines (RNH2)


(c) Reaction with Grignard reagents to yield ketones



Febuxostat is a xanathine oxidase(XO) inhibitor indicated in patients with gout suffering from hyperuricemia and is used in its chronic management

MilrinoneIndicated for the treatment of congestive heart failure

Ruxolitinibindicated to treat bone marrow cancer specifically intermediate or high-risk myelofibrosis

Saxagliptinorally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 inhibitor class of drugs

References

httpswwwamazoncomOrganic-Chemistry-Paula-Yurkanis-Bruice-ebookdpB01B7OIMJS

McMurry J E 2012 Organic Chemistry 8th Edition Brooks Cole Pub USA (ISBN 978-0495118374)

Klein DR 2012 Organic Chemistry as a Second Language Book 1 and 2

Fessenden RJ and Fessenden JS 1982 Organic Chemistry PWS Publisher

httpsdrivegooglecomfiled1sAZjTk9eMMzveBMea3QxNAwBLrhKpvNfviewusp=sharing

Learning objectives

In this session the students are able to describe the properties of carboxylic acids their general synthesis and reactivity and the example of carboxylic acid drugs


1 Naming

2 Properties

3 General Synthesis



1 Naming



Systematic Name


Common Name1 Naming

2 Properties





-






2 Properties





2 Properties


2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References







1 Naming

2 Properties

3 General Synthesis



1 Naming



Systematic Name


Common Name1 Naming

2 Properties





-






2 Properties





2 Properties


2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References






1 Naming



Systematic Name


Common Name1 Naming

2 Properties





-






2 Properties





2 Properties


2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References







Common Name1 Naming

2 Properties





-






2 Properties





2 Properties


2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References






2 Properties





-






2 Properties





2 Properties


2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References










2 Properties





2 Properties


2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References










2 Properties


2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References







2 Properties

3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References






3 General Synthesis






3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References








3 General Synthesis




3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References









3 General Synthesis

LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References






LiAlH4








Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References












Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References











Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References






Contents Nitriles

1 Naming

2 Properties

3 General Synthesis



1 Naming










2 Properties




2 Properties

3 General Synthesis























References






1 Naming










2 Properties




2 Properties

3 General Synthesis























References









2 Properties




2 Properties

3 General Synthesis























References









2 Properties

3 General Synthesis























References






3 General Synthesis























References

























References






















References




















References

















References















References













References











References






References






Documents

[Session 7] - cdn.i3l.ac.id