Nomenclature
Three examples of acyl groups having specific names were noted earlier. These
are often used in common names of compounds. In the following examples the
IUPAC names are color coded, and common names are given in parentheses.
• Esters: The alkyl group is named first, followed by a derived name for the
acyl group, the oic or ic suffix in the acid name is replaced by ate.
e.g.
CH3(CH2)2CO2C2H5
is
ethyl
butanoate
(or
ethyl
butyrate).
Cyclic esters are called lactones. A Greek letter identifies the location of the
alkyl oxygen relative to the carboxyl carbonyl group.
• Acid Halides: The acyl group is named first, followed by the halogen
name as a separate word.
e.g. CH3CH2COCl is propanoyl chloride (or propionyl chloride).
• Anhydrides: The name of the related acid(s) is used first, followed by the
separate word "anhydride".
e.g. (CH3(CH2)2CO)2O is butanoic anhydride & CH3COOCOCH2CH3 is
ethanoic propanoic anhydride (or acetic propionic anhydride).
• Amides: The name of the related acid is used first and the oic acid or ic
acid suffix is replaced by amide (only for1º-amides).
e.g. CH3CONH2 is ethanamide or acetamide.
2º and 3º-amides have alkyl substituents on the nitrogen atom. These are
designated by "N-alkyl" term(s) at the beginning of the name.
e.g. CH3(CH2)2CONHC2H5 is N-ethylbutanamide; and HCON(CH3)2 is N,Ndimethylmethanamide (or N,N-dimethylformamide).
Cyclic amides are called lactams. A Greek letter identifies the location of the
nitrogen on the alkyl chain relative to the carboxyl carbonyl group.
• Nitriles: Simple acyclic nitriles are named by adding nitrile as a suffix to
the name of the corresponding alkane (same number of carbon atoms).
Chain numbering begins with the nitrile carbon. Commonly, the oic acid or ic
acid ending of the corresponding carboxylic acid is replaced by o nitrile.
A nitrile substituent, e.g. on a ring, is named carbonitrile.
e.g. (CH3)2CHCH2C≡N is 3-methylbutanenitrile (or isovaleronitrile).
Function
Reagent
Aldehydes
& Ketones
H2
& catalyst
alcohols
( slow, Pt, Pd
)
(v. slow)
NaBH4
polar solvent
alcohols
LiAlH4
ether or THF
Carboxylic Carboxylic
Acids
Esters
Acyl
Chlorides
Amides
Nitriles
(v. slow)
aldehydes
( Pd/BaSO4
)
(v. slow)
amines
( Ni cat. )
N.R.
alcohols
(slow)
complex
mixture
N.R.
N.R.
alcohols
1º-alcohol
alcohols
1º-alcohol
amines
1º-amine
LiAlH(Ot-Bu)3
1 eq. in THF
alcohols
(slow at 0º)
N.R.
v. slow
aldehyde
(-78 º C)
aldehyde aldehyde
(-78 º C)
(0 º C)
(iso-Bu)2AlH
1 eq. in
toluene
alcohols
1º-alcohol
aldehyde
(-78º C)
1º-alcohol
aldehyde aldehyde
(-78 º C) (-78 º C)
B2H6
THF
alcohols
(slow)
1º-alcohol
(v. slow)
complex
mixture
1º-amine
1º-amine
Reactions at the α-Carbon
Many aldehydes and ketones were found to undergo electrophilic substitution at an
alpha carbon. These reactions, which included halogenation, isotope exchange
and the aldol reaction, take place by way of enol tautomer or enolate anion
intermediates, a characteristic that requires “at least one hydrogen on the αcarbon atom”. In this section similar reactions of carboxylic acid derivatives will be
examined. Formulas for the corresponding enol and enolate anion species that
may be generated from these derivatives are drawn in the following diagram.
Acid-catalyzed alpha-chlorination and bromination reactions proceed more slowly
with carboxylic acids, esters and nitriles than with ketones. This may reflect the
smaller equilibrium enol concentrations found in these carboxylic acid derivatives.
Nevertheless, acid and base catalyzed isotope exchange occurs as expected;
some examples are shown in equations #1 and #2 below. The chiral alpha-carbon
in equation #2 is racemized in the course of this exchange, and a small amount of
nitrile is hydrolyzed to the corresponding carboxylic acid.
Acyl halides and anhydrides are more easily halogenated than esters and nitriles,
probably because of their higher enol concentration. This difference may be used
to facilitate the alpha-halogenation of carboxylic acids. Thus, conversion of the acid
to its acyl chloride derivative is followed by alpha-bromination or chlorination, and
the resulting halogenated acyl chloride is then hydrolyzed to the carboxylic acid
product. This three-step sequence can be reduced to a single step by using a
catalytic amount of phosphorus tribromide or phosphorus trichloride, as shown in
equation #3. This simple modification works well because carboxylic acids and acyl
chlorides exchange functionality as the reaction progresses. The final product is
the alpha-halogenated acid, accompanied by a trace of the acyl halide. This
halogenation
procedure
is
called
the
Hell-Volhardt-Zelinski
reaction.
In a similar fashion, acetic anhydride serves as a halogenation catalyst for acetic
acid (first equation below). Carboxylic acids that have a higher equilibrium enol
concentration do not need to be activated for alpha-halogenation to occur, as
demonstrated by the substituted malonic acid compound in the second equation
below. The enol concentration of malonic acid (about 0.01%) is roughly ten
thousand times greater than that of acetic acid. This influence of a second
activating carbonyl function on equilibrium enol concentrations had been noted
earlier in the case of 2,4-pentanedione.
heat
(i) CH3-CO2H + Br2 & (CH3CO)2O catalyst
(ii) RCH(CO2H)2 + Br2
BrCH2CO2H + HBr
RCBr(CO2H)2 + HBr
To illustrate the general nucleophilic reactivity of di-activated enolate anions, two
examples of SN2 alkylation reactions are shown below. Malonic acid esters and
acetoacetic acid esters are commonly used starting materials, and their usefulness
in synthesis will be demonstrated later in this chapter. Note that each of these
compounds has two acidic alpha-hydrogen atoms (colored red). In the equations
written here only one of these hydrogens is substituted; however, the second is
also acidic and a second alkyl substitution may be carried out in a similar fashion.
Claisen Condensation
The aldol reaction, is a remarkable and useful reaction of aldehydes and ketones in
which the carbonyl group serves both as an electrophilic reactant and the source of
a nucleophilic enol species. Esters undergo a similar transformation called the
Claisen Condensation. Four examples of this base-induced reaction, which
usually forms beta-ketoester products, are shown in the following diagram. Greek
letter assignments for the ester products are given in blue. Equation #1 presents
the synthesis of the important reagent ethyl acetoacetate, and #2 illustrates the
general form of the Claisen condensation. Intramolecular reactions, such as #3,
lead to rings (usually five or six-membered) and are referred to as Dieckmann
Condensations. The last equation shows a mixed condensation between two
esters, one of which has no alpha-hydrogens. The product in this case is a phenyl
substituted malonic ester rather than a ketoester.
Analise estrutural:
The Claisen condensation differs from the aldol reaction in
several important ways.
1-The aldol reaction may be catalyzed by acid or base, but most Claisen
condensation requires base.
2- In contrast to the catalytic base used for aldol reactions, a full equivalent
of base (or more) must be used for the Claisen condensation. The extra
base is needed because beta-ketoesters having acidic hydrogens at the
alpha-carbon are stronger acids (by about 5 powers of ten) than the alcohol
co-product. Consequently, the alkoxide base released after carbon-carbon
bond formation (upper right structure in the mechanism diagram)
immediately removes an alpha proton from the beta-ketoester product. As
noted above, formation of this doubly-stabilized enolate anion provides a
thermodynamic driving force for the condensation.
3-The aldol reaction may be catalyzed by hydroxide ion, but the Claisen
condensation requires that alkoxide bases be used, in order to avoid ester
hydrolysis. The specific alkoxide base used should match the alcohol
component of the ester to avoid ester exchange reactions. Very strong
bases such as LDA may also be used in this reaction.
4-The stabilized enolate product must be neutralized by aqueous acid in
order to obtain the beta-ketoester product.
Reactions of Claisen Products
The Claisen condensation produces beta-ketoesters. These products may then be
modified or enhanced by further reactions. Among these, the following diagram
illustrates (i) partial reduction of the ketone with NaBH4, (ii) complete reduction to a
1,3-diol by LiAlH4, (iii) enolate anion alkylation, and (iv) ester hydrolysis followed by
thermal decarboxylation of the resulting beta-ketoacid.
Acidity of Carboxylic Acids
The pKa 's of some typical carboxylic acids are listed in the following table. When
we compare these values with those of comparable alcohols, such as ethanol (pK a
= 16) and 2-methyl-2-propanol (pKa = 19), it is clear that carboxylic acids are
stronger acids by over ten powers of ten! Furthermore, electronegative substituents
near the carboxyl group act to increase the acidity.
Compound
pKa
Compound
pKa
HCO2H
3.75
CH3CH2CH2CO2H
4.82
CH3CO2H
4.74
ClCH2CH2CH2CO2H
4.53
FCH2CO2H
2.65
CH3CHClCH2CO2H
4.05
ClCH2CO2H
2.85
CH3CH2CHClCO2H
2.89
BrCH2CO2H
2.90
C6H5CO2H
4.20
ICH2CO2H
3.10
p-O2NC6H4CO2H
3.45
Cl3CCO2H
0.77
p-CH3OC6H4CO2H
4.45
Why should the presence of a carbonyl group adjacent to a hydroxyl group have
such a profound effect on the acidity of the hydroxyl proton? To answer this
question we must return to the nature of acid-base equilibrium and the definition of
pKa , illustrated by the general equations given below. These relationships were
described in a previous section of this text.
We know that equilibrium favors the thermodynamically more stable side, and that
the magnitude of the equilibrium constant reflects the energy difference between
the components of each side. In an acid base equilibrium the equilibrium always
favors the weaker acid and base (these are the more stable components). Water is
the standard base used for pKa measurements; consequently, anything that
stabilizes the conjugate base (A:(–)) of an acid will necessarily make that acid (H–A)
stronger and shift the equilibrium to the right. Both the carboxyl group and the
carboxylate anion are stabilized by resonance, but the stabilization of the anion is
much greater than that of the neutral function, as shown in the following diagram.
In the carboxylate anion the two contributing structures have equal weight in the
hybrid, and the C–O bonds are of equal length (between a double and a single
bond). This stabilization leads to a markedly increased acidity, as illustrated by the
energy diagram
1. Indicar os substratos e reagentes necessários para obter os compostos abaixo via
reaçao de Grignard
2. Como obter os compostos a partir de Compostos carbonílicos
3. Indicar as condições e o produto de hidrólise dos Acetais ou Cetais indicados
4. Indicar os produtos das seqüências reacionais indicadas
5. Indicar o produto da reação da 2-butilamina com
6. Indicar a enolização e qual o tautômero prevalece no equilíbrio
7. Indicar as condições reacionais e o produto das reações
8. Indicar a reação para
a) caracterizar uma olefina
b) caracterizar um álcool primário
c) caracterizar haleto primário
d) caracterizar um aldeído
e) diferenciar aldeído de cetona
9. Qual o procedimento para identificar as estruturas abaixo via reação química
10.Quais as reações para obter o produto indicado ? ( Cetonas são mais reativas que
Ésteres)
1. Indicar os substratos e reagentes necessários para obter os compostos abaixo via
reaçao de Grignard
2. Como obter os compostos a partir de Compostos carbonílicos
3. Indicar as condições e o produto de hidrólise dos Acetais ou Cetais indicados
4. Indicar os produtos das sequencias reacionais indicadas
5. Indicar o produto da reação da 2-butilamina com
6. Indicar a enolização e qual o tautômero prevalece no equilíbrio
7. Indicar as condições reacionais e o produto das reações
8. Indicar a reação para
a) caracterizar uma olefina positivo quando há o descoramento da solução de
Br2/CCl4
b) caracterizar um álcool primário usar solução de Jones CrO3 (cor laranja passa a
verde-azulado)
c) caracterizar haleto primário usar solução de NaI /Acetona (positivo quando
precipita NaX)
d) caracterizar um aldeído
Reagente de Tollens Ag(NH3)2 positivo quando
forma espelho de prata
e) diferenciar aldeído de cetona Reagente de Tollens (só para Aldeídos) ou 2,4
DNPH
9. Qual o procedimento para identificar as estruturas abaixo via reação química
usar resposta da questão 8
10.Quais as reações para obter o produto indicado ? ( Cetonas são mais reativas que
Ésteres)
EXERCÍCIOS
REAÇÕES DE ÁCIDOS CARBOXÍLICOS
1. Complete as reações
a) CH3CH2CH2CH2OH + Cr2O7- ...............
b) Vanilina + Ag(NH3)2 .................
c) CH3CH2CH2CH2Br + Mg/éter à............ + CO2 ....................
d) CH3CH2CH2OCH = CHCH2COOH + KmnO4/ KOH/água
...................................
e) CH3CH2CH2CH2C=O(CH3) + I2 /KOH ...........................
2. Indicar a reação para preparar o ácido correspondente a partir de
a) 1-pentanol
b) Pentanal c) 1-Penteno
d) 1-bromopropano
e) 2hexanona
f) Tolueno
g) Estireno
h) Acetofenona i) Cloreto de t-Butila + Mg
3. Indicar usando fórmulas estruturais para as equaçõe abaixo
a) C6H14O oxidação CH3(CH2)4COOH
b) C6H14O2 oxidação COOH(CH2)4COOH
c) CO6H12O oxidação CH3(CH2)4COOH
4. Atribua o pKa a estrutura correspondente e justifique
a) ácido benzóico
b) p-nitro benzóico c) p-amino benzóico
d) ácido benzenosulfônico e) ácido propanóico f) ácido 2-hidróxipropanóico
usar os pKa = 5 ; 4,8 ; 4,2 ; 3,2; 3 e 0,7
5. Ácidos dicarboxílicos apresentam dois valores de pka sendo que a ionização do
primeiro é mais fácil .
Justifique porque quanto maior a cadeia menor a diferença entre os pKa
Ácido Fórmula
Oxálico
HOOC-COOH
pKa1
pKa2
1,2
4,2
Malônico COOH(CH2)COOH
2,8
5,7
Succínico COOH(CH2)2COOH
4,2
5,6
Glutárico COOH(CH2)3COOH
4,3
5,4
Adípico COOH(CH2)4COOH
4,4
5,4
6. Qual o átomo em cada molécula reage com o H+ para gerar o carbocatíon
7. Colocar em ordem crescente de acidez
Metanol, Fenol, p-Nitrofenol, ácido benzóico, ácido p- amino benzóico, ácido
acético
8. Qual a reação entre o ácido fenilacético (PhCH2COOH) e 1,0 equivalente dos
reagentes
a) SOCl2
b) PCl3 c) NaOH/ água d) MeMgBr / éter e) MeOH / H+
9. Indicar as transformações butanal a 2-etil-2-hexenal e para ácido 2-etil-2hexenóico
10- Indicar o nome dos compostos e como esterificar estes ácidos
11- Indicar as estruturas de ressonância da acetona e do ácido acético. A partir das
estruturas de ressonância indicadas comparar a reatividade
12- Colocar em ordem de acidez os ácidos
14- Justifique : O pka do íon oxônio = -3, da acetona protonada é -7,2 e do ác
acético protonado é -6
15- Como obter os ácidos carboxílicos indicados abaixo(mais que um passo pode
ser necessário)
16- Indicar duas rotas de obtenção para CH3(C=O)-O-(C=O)C2H5 e
(CH3)2CH(C=O)Cl
17- Indicar o caminho reacional para obter a lactona B