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,N-dimethylmethanamide (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).

FunctionReagent Aldehydes

& KetonesCarboxylic

AcidsCarboxylic

EstersAcyl

Chlorides Amides Nitriles

H2

& catalyst

alcohols( slow, Pt,

Pd )(v. slow) (v. slow) aldehydes

( Pd/BaSO4 )(v. slow) amines

( Ni cat. )

NaBH4

polar solvent alcohols N.R. alcohols

(slow)complexmixture N.R. N.R.

LiAlH4

ether or THFalcohols 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(-78 º C)

aldehyde(0 º C)

(iso-Bu)2AlHalcohols 1º-alcohol aldehyde

(-78º C)1º-alcohol aldehyde

(-78 º C)aldehyde(-78 º C)

1 eq. in toluene

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 α-carbon 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

(i) CH3-CO2H   +   Br2   &   (CH3CO)2O catalyst heat

BrCH2CO2H   +   HBr

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.

(ii) RCH(CO2H)2   +   Br2 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 (pKa

= 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) 2-hexanona 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  pKa1  pKa2Oxálico    HOOC-COOH  1,2 4,2Malônico COOH(CH2)COOH  2,8  5,7Succínico COOH(CH2)2COOH  4,2  5,6Glutárico COOH(CH2)3COOH  4,3  5,4Adípico 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-2-hexenóico

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