18
CARBOXYLIC CHAPTER ACIDS & DERIVATIVES
- - INTRODUCTION, NOMENCLATURE, PHYSICAL PROPERTIES - - SYNTHESIS OF: RCO2H & DERIVATIVES - - REACTIONS OF: ACIDS & DERIVATIVES - - HELL-VOLHARD-ZELINSKI REACTION - - DERIVATIVES OF H2CO3 - - DECARBOXYLATION OF RCO2H - - CHEMICAL ANALYSES
INTRODUCTION:
- - CARBOXYLIC ACIDS: RCO2H - - DERIVATIVES: - - SEE TABLE 18.1 p. 811 - - COMMON FEATURES ?
O C R OH
NOMENCLATURE:
- - CARBOXYLIC ACIDS: ALKANOIC ACID - - SEE TABLE 18.2 p. 812 - - SALTS: e.g. RCO2 Na+ (K+) - - SODIUM ALKANOATE
- - DO PROBLEM: 18.1 p. 813 - - DICARBOXYLIC ACIDS - - ALKANEDIOIC ACIDS
- - SEE TABLE 18.3 p. 815 - - ESTERS:
O C R O R' ALKYL
ALKANOATE
NAME: ALKYL ALKANOATE - - SEE TABLE 18.4 p. 816
O R O O R
- - ACID ANHYDRIDES: ALKANOIC ANHYDRIDE ( p. 816 )
O C R X
- - ACYL HALIDES: ALKANOYL HALIDE
- - SEE e.g. p. 816 - - AMIDES:
O C R NH2
ALKANAMIDE
O C R N R'
H - - N SUBSTITUTED AMIDES
O C R N R" R'
N ALKYL ALKANAMIDE N,N DIALKYL ALKANAMIDE e.g. DMF ( ? )
- - NITRILES: RCN ALKANENITRILE
- - IF CN IS A SUBSTITUENT: " CYANO " DO PROBLEM: 18.5 p. 817 18.20 p. 858
PHYSICAL PROPERTIES:
- - SEE TABLES 18.2 , 18.3 , 18.4 - - EXAMINE TRENDS IN: M.P. , B.P. , WATER SOLUBILITY , pKa , etc.
DO PROBLEMS: 18.2 , 18.3 , 18.4
- - B.P. OF RCOX & RCO-O-COR - - SIMILAR TO: RCO2R' ( WITH COMPARABLE MW )
- - AMIDES: DEPENDS ON WHETHER PROTIC / APROTIC ( p. 817 )
SPECTROSCOPIC ANALYSES
- - STUDY ON YOUR OWN ! ( MOSTLY REVIEW ! ) - - DO PROBLEM : 18.36 p. 860
18.40 p. 862
SYNTHESIS OF: RCO2H
- - 1] FROM >C=C< : HOW ?
- - 2] FROM RCHO , RCH2OH : HOW ? - - 3] FROM Ar-R: HOW ? - - 4] FROM RCOCH3 : HOW ? - - 5] FROM R-CN : HOW ?
- - 6] FROM RMgX : HOW ? DO PROBLEMS: 18.6 18.8 p. 822
SYNTHESIS OF: RCOX
- - FROM RCO2H - - SEE p. 825 - - REAGENTS: ? - - MECHANISM: SEE p. 826
SYNTHESIS OF: RCO-O-COR'
- - SEE p. 827 - - FUNCTION OF PYRIDINE ( C6H5N ) ? ( cf. WILLIAMSON ETHER SYNTHESIS ) - - CYCLIC ANHYDRIDES WITH 5 / 6 MEMBERED RING ( INTRAMOLECULAR DEHYDRATION ) - - WHY IS DEHYDRATION SO EASY ? - - CONSIDER: STABILITY & ENTROPY - - DO PROBLEM: 18.9 p. 828
SYNTHESIS OF: RCO2R'
- - FROM (RCO2H + R'-OH ) - - SEE p. 828 - - INTERMOLECULAR DEHYDRATION - - MECHANISM: SEE p. 829 - - SUPPORTING EVIDENCE ? - - H3O+ CATALYSIS - 18
O LABELING STUDIES
- - FROM : ( RCOX + R'-OH ) - - SEE p. 830 - - ROLE OF PYRIDINE ? - - FROM (RCO-O-COR + R'-OH ) - - SEE p. 831 - - TRANSESTERIFICATION - - SEE PROBLEM : 18.11 p. 831 - - CONSTRAINTS ? - - LACTONES - - CYCLIC ESTERS - FROM : HYDROXY ACIDS - - SEE p. 834 - - INTRAMOLECULAR ESTERIFICATION - - e.g. VITAMIN C p. 835 - - FROM: HYDROXY ACIDS - - SEE p. 835 - - INTRAMOLECULAR DEHYDRATION LACTONE ? OR
?
UNSATURATED ACID
- - FROM: HYDROXY ACIDS - - SEE p. 836 - - WHAT IS A STABILIZING FEATURE IN A LACTIDE ? - - MACROCYCLIC LACTONE: - - e.g. ERYTHROMYCIN A
SYNTHESIS OF AMIDES: RCONH2 (-NHR, -NR2)
- - FROM : ( RCOX + H-N< ) - - p. SEE 836 - - FROM: ( RCO-O-COR + H-N< ) - - SEE p. 837
- - FROM: ( RCOOR' + H-N< ) - - SEE p. 838 - - FROM: RCOOH RCOO NH4+ RCONH2 - - REACTION TYPES ?
- - SEE p. 839 ( GENERALLY: NOT A VERY EFFICIENT PROCESS ! ) - - WITH DCC - - SEE p. 839
SYNTHESIS OF: RCN
- - SEE p. 841 1] FROM RX: HOW ? SN2 REACTIONS - - SEE p. 261 2] FROM RCONH2 HOW ?
REACTIONS OF ACIDS & DERIVATIVES:
- - AT THE ACYL CARBON: - - Nu: ADDITION, FOLLOWED BY - - ELIMINATION - - SEE MECHANISM p. 823 cf.: Nu: ADDITION TO >C=O OF ALDEHYDES AND KETONES p. 823
- - ELIMINATION FACILITATED BY GROUP " L " : ( LEAVING GROUP ) OVERALL: REACTION IS SUBSTITUTION OF " L "
WHY DOES SIMILAR ELIMINATION NOT OCCUR WITH ALDEHYDES & KETONES ? ( NO GOOD " L " ! ) - - SEE p. 824 - - RELATIVE REACTIVITY - - SEE SECTION 18.4B p. 825 - - SEE FIG. 18.4 B p. 828 - - HYDROLYSIS: - - RCOCl - - SEE p. 827 - - RCO-O-OCR - - SEE p. 828 - - RCOOR' - - SEE p. 832 cf. ACID-CATALYSED ESTERIFICATION, REVERSED !
- - BASE PROMOTED : " SAPONIFICATION " - - MECHANISM - - SEE p. 832 - - SUPPORTING EVIDENCE - 18
O LABELING STUDIES
- - RETENTION OF CONFIGURATION AT ALKYL CARBON [ cf. REACTION WITH SULFONIC ESTERS ] - - DO PROBLEM: 18.12 p. 833 18.13 p. 834
- - RCON< - - SEE p. 840 841 - - DO PROBLEM: 18.14 p. 841 - - R-CN - - SEE p. 842 843 - - LACTAMS: - - CYCLIC AMIDES - - SEE p. 843 ( cf. LACTONES ):
SEE p. 844
HELL-VOLHARD ZELINSKI REACTION:
- - -HALO ACIDS - - SEE p. 844 845 - - ALTERNATIVE - - ACYL HALIDE + + - - SIGNIFICANCE ? - - -HALOGEN CAN BE SUBSTITUTED BY A VARIETY OF Nu: ( SN1 / SN2 ) - - SEE e.g. p. 845 846 + NCS I2 NBS
DERIVATIVES OF CARBONIC ACID:
H2CO3 : (OH)2 C = O - - USE ACYL HALIDE TO MAKE THE VARIOUS DERIVATIVES - - CARBONYL DICHLORIDE: O = CCl2 " PHOSGENE " : TOXIC !
- - ALKYL CHLOROFORMATES & CARBAMATES - - SEE p. 847
OH H O ? Cl O CHLOROFORMIC ACID ? OH Cl O OR
- - ALKYL CHLOROFORMATES
N< OR O ESTER AMIDE
- - CARBAMATE = (ESTER + AMIDE) ON SAME CARBON
R
O H
+
R
N
C
O
R N H C
O OR
- - ALTERNATIVE SYNTHESIS OF CARBAMATES - - SEE p. 847-848 METHYL ISOCYANATE: VERY TOXIC ! BHOPAL TRAGEDY: 1984 - - DO PROBLEM: 18.16 p. 848
OH HO O Cl
OH RO O
OH H2N O
OH O
- - STABILITY: UNSTABLE ! - - SPONTANEOUS DECOMPOSITION - - SEE p. 848
DECARBOXYLATION:
R-CO2H NOT EASY ! EXCEPT ............ - - -KETO ACIDS OR CARBOXYLATES - - SEE MECHANISMS: p. 849 - - e.g. - - ACETOACETIC ACID - - MALONIC ACID ( SYNTHETIC UTILITY: CHAPTER 19 ) R-H + CO2
- -
ArCO2H - - VIA ArCO2Cu - - SEE p. 851
- - RCO2 - - CARBOXYLATE RADICALS - - SEE p. 851
CHEMICAL ANALYSIS:
STUDY ON YOUR OWN ! - - RCO2H: DISSOLVE IN : - NaOH ( ? ) - - NaHCO3 ( ? ) - - Na2CO3 ( ? ) - - RCOCl: HYDROLYZE IN WATER ( ? ) - - HOW TO DETECT THIS ? (AgNO3) - - RCO-O-OCR: DISSOLVE IN NaOH UPON HEATING - - WHY ? (?) - - RCO2R', RCONH2: HYDROLYZE WITH NaOH ( ? ) - - REFLUX - - DETECTION ? - - IDENTIFICATION ?