16 Carbonyl Compounds I. Aldehydes and Ketones. Addition Reactions of the Carbonyl Group
Table of General Methods for the Preparation of Ketones
16 Carbonyl Compounds I. Aldehydes and Ketones. Addition Reactions of the Carbonyl Group
Supplementary Exercises
Supplementary Exercises
16-48 Write equations for the synthesis of the following substances based on the indicated starting materials. Give the reaction conditions as accurately as possible.
a.2-methyl propanal from 3-methyl butanol
b.I-cyclobutylethanone from cyclobutanecarboxylic acid
c.pentanedial from cyclopentanone
d.cyclobutane from methylenecyclobutane
e.2,2,2-trichloroethyl trichloroethanoate from 2,2,2-trichloroethanal
f.cyclopentene-1-carboxylic acid from cyclopentanone
16-49 Write reasonable mechanisms for each of the following reactions. Support your formulations with detailed analogies insofar as possible.
0 |
0 |
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II |
II |
+ NaOH |
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a. H-C-C-H |
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HOCH2C02Na |
(Notice that this is a base-catalyzed reaction.)
d. Hexamethylenetetramine from methanal and ammonia. (Consider the possibility of CH2=NH as an intermediate for the stepwise formation of N,N1,N"-tris(hydroxy- methyl)-I,3,5-triazacyclohexane as an intermediate followed by acid-induced condensation of the latter with ammonia.)
16-50 It is important to be able to decide whether a plausible-looking reaction actually will proceed as written. The following equations represent "possible" synthetic reactions. Consider each carefully and decide whether it will proceed as written. Show your reasoning. If you think another reaction would occur, write an equation for it.
excess
a. CH3CH(OC2H5),+ 2NaOCH3 CH OH CH3CH(OCH3),+ 2NaOC2H5
2
50"
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b. (CH,),CCOCH,CH, + KMnO, |
H 0 |
(CH,),COH |
+ CH3CH2C02K |
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KOH |
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734 16 Carbonyl Compounds I. Aldehydes and Ketones. Addition Reactions of the Carbonyl Group
e. |
O=CH-C0,H |
CH OH |
+ NaBH, A O=CH-CH,OH |
f. |
CH,=O + (CH,),C=O + NaOH -HC0,Na + (CH,),CHOH |
16-51 Write a mechanism for the oxidation of sodium methanoate (formate) to carbon dioxide by potassium permanganate which is consistent with the following facts:
(a)v = k[HCO,@][MnO,@]
(b)the CO, has no 180in it if oxidized with Mni804@
(c)DCO,@ is oxidized at one seventh the rate of HCO,@
Compare your mechanism with that generally accepted for the Cannizzaro reaction.
16-52 2-Propanone reacts with trichloromethane in the presence of potassium hydroxide to give 1, I,I-trichloro-2-methyl-2-propanol. What is likely to be the mechanism of this reaction? What further evidence could be gained to establish the mechanism? (If you do not see a possible answer, refer to Section 14-7B for helpful information.)
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16-53 The |
structure of the sex attractant. of the silkworm, "bombykol," is given in |
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Section 5-6 as structure 30. The compound has been synthesized by the route given |
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below. Write the structures of each of the synthetic intermediates A-F. |
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NaC=CH |
1. CH,MgCI |
PBr, |
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CH,CH,CH,Br |
-A |
2 HCHO |
> B - C |
, |
C |
(C H ) P |
1 . base (C2H50Na) |
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E H2, Pd |
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F |
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2. O=CH(CH2),C02C2H5 |
'(Llndlar) |
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F |
LiAIH, |
"bombykol" |
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------+ |
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7
CARBONYL COMPOUNDS ENOLS AND ENOLATE
ONS. UNSATURATED AND POLYCARBONYL COMPOUNDS
ome of the most useful reactions of carbonyl compounds involve carbonhydrogen bonds adjacent to the carbonyl group. Such reactions, which can be regarded as the backbone of much synthetic organic chemistry, usually result in the replacement of the hydrogen by some other atom or group, as in the
I I |
I I |
The important examples we |
sequence H-C-C=O |
-+ X-C-C=O. |
I |
I |
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will consider in this chapter are halogenation, alkylation, and aldol reactions of aldehydes and ketones, illustrated here for 2-propanone:
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Br |
halogenation |
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0 |
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C |
CH,I |
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I/ |
/CH3 |
alkylation |
cH/, |
\CH, |
'cH/, |
C |
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\CH, |
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I |
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736 17 Carbonyl Compounds II. Enols; Enolate Anions. Unsaturated and Polycarbonyl Compounds
Although these reactions lead to many diverse products depending on the reagents and conditions, they have one feature in commonthey proceed by way of the en01 or the enolate anion of the parent carbonyl compound:
carbonyl form |
enolate anion |
enol form |
Therefore, to understand the nature of these reactions we first must understand the conditions that convert aldehydes and ketones to their en01 forms or the anions of those en01 forms.
17-1 ENOLIZATION OF ALDEHYDES AND KETONES
Transformation of a carbonyl compound to an en01 at a useful rate normally requires either a basic catalyst or an acidic catalyst and, of course, at least one hydrogen on the a carbon. The features of each type of catalysis follow.
17-1A Enolization in Basic Solution.
C-H Acidity of Carbonyl Compounds
With a basic catalyst such as hydroxide ion, the first step in enolization is removal of a proton from the a position to give the enolate anion 1:
Normally, C-H bonds are highly resistant to attack by basic reagents, but removal of a proton alpha to a carbonyl group results in the formation of a considerably stabilized anion with a substantial proportion of the negative charge on oxygen, as represented by the valence-bond structure la . Carbonyl compounds such as 2-propanone therefore are weak acids, only slightly weaker than alcohols (compare the pK, values for some representative compounds in Table 17-1).l
lThe important difference between 2-propanone and ethanol as acids is that the rate of establishment of equilibrium with 2-propanone or similar compounds where ionization involves breaking a C-H bond is very much slower than the corresponding reaction with 0 - H bonds.
17-1 Enolization of Aldehydes and Ketones |
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Table 17-1 |
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C-H and 0-H |
Acidities of Some Representative Compoundsa |
C-H |
Acidity |
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0 - H Acidity |
Compound |
PKa |
Compound |
PK.3 |
0 |
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II |
25 |
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RO-C-CH, |
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"These are approximate values; the acidic hydrogen is shown in boldface type; pKa is defined in Section 8-1.
Two carbonyl groups greatly increase the acidity. For example, 2,4- pentanedione (acetylacetone, 2) has a pK, = 9, which is comparable to the 0-H acidity of phenols (see Table 17-1). The reason is that the enolate anion 3 has the charge largely shared by the two oxygen atoms (cf. 3b and 3c). As a result, the enolate anion 3 is stabilized more with respect to the
738 17 Carbonyl Compounds 11. Enols; Enolate Anions. Unsaturated and Polycarbonyl Compounds
ketone than the enolate anion from 2-propanone is stabilized relative to 2-propanone:
: o : |
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: o : |
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-0 |
:o: |
: o : |
-0 |
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: o . |
: o . |
II |
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II |
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I |
II |
I/ |
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I |
,C\@ |
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,c\ |
CH, - |
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C |
- C |
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C |
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cH/, |
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,\ |
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CH, |
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\CH |
CH, |
cH/, |
\~6 |
C. |
H |
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\CH, |
Exercise 17-1 Other groups in addition to carbonyl groups enhance the acidities of adjacent C-H bonds. For instance, nitromethane, CH3N02,has pK, = 10; ethanenitrile, CH3CN,has a pK, = 25. Explain why these compounds behave as weak acids. Why is CH3COCH, a stronger acid than CH3C02CH3?
Exercise 17-2 Draw valence-bond structures to represent the anions derived from the following compounds in the presence of a strong base. Assume that the base functions to remove the most acidic proton.
17-1B Enol Formation from Enolate Anions
You will notice from Structures l a and I b that because the negative charge of the enolate anion is distributed on both oxygen and carbon, the ion can, in principle, combine with a proton at either site. If the enolate ion adds a proton to oxygen,the en01is formed; if it adds a proton to carbon, the ketone is formed:
en01
