Claisen Condensation

5 Key excerpts on "Claisen Condensation"

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  eBook - PDF

  Brown's Introduction to Organic Chemistry

  • William H. Brown, Thomas Poon(Authors)
  • 2017(Publication Date)
  • Wiley

    (Publisher)

  Claisen Condensation A carbonyl condensation reaction between two esters to give a β‐ketoester. Claisen Condensation As you study this mechanism, note how closely its first two steps resemble the first steps of the aldol reaction (Section 15.1). In each reaction, base removes a proton from an α-carbon in Step 1 to form a resonance‐stabilized enolate anion. In Step 2, the enolate anion attacks the carbonyl carbon of another ester molecule to form a tetrahedral carbonyl addition intermediate. 15.3 Mechanism 516 C H A P T E R 15 Enolate Anions STEP 1: Take a proton away. Base removes an α‐hydrogen from the ester to give a resonance‐stabilized enolate anion: Resonance-stabilized enolate anion (weaker base) (weaker acid) (stronger (stronger base) acid) pK a 15.9 pK a 22 EtOH CH 2 O COEt CH 2 O COEt EtO H CH 2 O COEt – – – Because the α‐hydrogen of the ester is the weaker acid and ethoxide is the weaker base, the position of this equilibrium lies very much toward the left. STEP 2: Reaction of an electrophile and a nucleophile to form a new covalent bond. Attack of the enolate anion on the carbonyl carbon of another ester molecule gives a tetrahedral carbonyl addition intermediate: A tetrahedral cabonyl addition intermediate (a nucleophile) (an electrophile) CH 3 O C OEt CH 2 O COEt CH 3 O C O CH 2 Et O C OEt new C C bond – – STEP 3: Collapse of the tetrahedral carbonyl addition intermediate to eject a leaving group and regenerate the carbonyl group. Unlike the tetrahedral carbonyl addition intermediate in the aldol reaction, this intermediate has a leaving group (the ethoxide ion). Collapse of the tetrahedral carbonyl addition intermediate by ejection of the ethoxide ion gives a β‐ketoester: CH 3 O C CH 2 O C OEt EtO CH 3 O C OEt CH 2 O C OEt – – STEP 4: Take a proton away. Formation of the enolate anion of the β‐ketoester drives the Claisen Condensation to the right.

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  eBook - PDF

  Introduction to Organic Chemistry

  • William H. Brown, Thomas Poon(Authors)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  Claisen Condensation In this section, we examine the formation of an enolate anion from one ester, followed by the nucleophilic acyl substitution of the enolate anion at the carbonyl carbon of another ester. One of the first of these reactions discovered was the Claisen Condensation, named after its discoverer, German chemist Ludwig Claisen (1851–1930). We illustrate a Claisen Condensation by the reaction between two molecules of ethyl acetate in the presence of sodium ethoxide, followed by acidification, to give ethyl acetoacetate (note that, in this and many of the equations that follow, we abbreviate the ethyl group as Et): Ethyl ethanoate Ethyl 3-oxobutanoate Ethanol (Ethyl acetate) (Ethyl acetoacetate) CH 3 O CCH 2 O COEt EtOH 1) EtO Na 2) H 2 O, HCl 2 CH 3 O COEt The functional group of the product of a Claisen Condensation is a β‐ketoester: A β -ketoester C O C β C α O C OR The Claisen Condensation of two molecules of ethyl propanoate gives the following β‐ketoester: 1) EtO – Na + 2) H 2 O, HCl Ethyl 2-methyl-3- oxopentanoate (racemic) Ethyl propanoate Ethyl propanoate + + EtOH OEt O O OEt O OEt O Claisen Condensations, like the aldol reaction, require a base. Aqueous bases, such as NaOH, however, cannot be used in Claisen Condensations because aqueous base would bring about hydrolysis of the ester (saponification, Section 14.3C) instead. Rather, the bases most commonly used in Claisen Condensations are nonaqueous bases, such as sodium ethoxide in ethanol and sodium methoxide in methanol. Furthermore, to prevent transes- terification (Section 14.4C), the alkyl group ( R) of the base should match the R group in the alkoxyl portion ( OR) of the ester. 15 Claisen Condensation A carbonyl condensation reaction between two esters to give a β‐ketoester. Mechanism Claisen Condensation As you study this mechanism, note how closely its first two steps resemble the first steps of the aldol reaction (Section 15.1).

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  eBook - ePub

  Principles of Organic Synthesis

  • Richard O.C. Norman(Author)
  • 2017(Publication Date)
  • Routledge

    (Publisher)

  The self-condensation of an ester which contains an α-hydrogen atom is known as the Claisen (ester) condensation. The simplest example is the formation of acetoacetic ester (ethyl 3-oxobutanoate) from ethyl acetate, catalyzed by ethoxide ion:

  The reaction is usually carried out by refluxing very dry ethyl acetate over sodium wire. The sodium reacts with the 2–3% of ethanol which is present in commercial ethyl acetate, generating ethoxide ion which then catalyzes the reaction. The product is obtained as the sodium salt of acetoacetic ester from which the free ester is liberated by treatment with acetic acid. Yields of about 30% are obtained [1].

  The Claisen Condensation differs from the aldol reaction only after the oxyanion has been formed by addition of the enolate to the carbonyl group: in the Claisen reaction this anion eliminates ethoxide ion to give a β-keto-ester, whereas in the aldol reaction the anion gains a proton to give a β-hydroxy-aldehyde or ketone.

  Each step in the Claisen Condensation is reversible, and acetoacetic ester can be isolated in significant yield only because it is essentially completely removed from equilibrium by conversion into its anion under the influence of ethoxide ion (i.e. acetoacetic ester is a much stronger acid than ethanol). However, in those cases in which the β-keto-ester product does not contain a C—H bond adjacent to both keto and ester groups so that this marked acidic character is absent, the equilibria are unfavourable to reaction when ethoxide ion is the base. For example, ethyl isobutyrate, Me2 CHCO2 Et, fails to give Me2 CH—CO—CMe2 —CO2 Et in these conditions. This problem can be surmounted by using a very much stronger base than ethoxide ion, and the triphenylmethide ion, added as sodium triphenylmethyl, is conveniently employed. This results in the essentially complete removal of the ethanol formed in the reaction:

  (i) Mixed reactions

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  eBook - ePub

  Applied Organic Chemistry

  Reaction Mechanisms and Experimental Procedures in Medicinal Chemistry

  • Surya K. De(Author)
  • 2020(Publication Date)
  • Wiley-VCH

    (Publisher)

  2 Condensation Reaction

  A condensation reaction is a broad class of organic addition reactions in which two or more identical or different molecules combine together typically proceed in a through stepwise fashion to form a single addition product with elimination of water (hence named condensation). Instead of water, the reaction can proceed with elimination of simple units like ammonia, ethanol, or acetic acid. The condensation reaction can occur in acidic, basic conditions or in the presence of other catalysts. This type of reactions is an essential part of our life as it is an important to form peptide bonds in between amino acids in protein and the biosynthesis of fatty acids.

  Condensation of two amino acids gives a peptide and water. Here we describe some named condensation reactions and more condensation reactions can be found in other chapters as well.

  Aldol Condensation Reaction

  Ketones with hydrogen on the carbon atom adjacent to the carbonyl group are called as α‐hydrogen, and it is very reactive in the presence of base or acid. On treatment with base benzaldehyde and acetophenone undergo a carbon–carbon bond‐forming reaction called the aldol condensation [1

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  Organic Chemistry, Student Study Guide and Solutions Manual

  • David R. Klein(Author)
  • 2017(Publication Date)
  • Wiley

    (Publisher)

  The  position is the location between the two carbonyl groups, and the  position bears the keto group: Since the two partners are different, we use a crossed Claisen Condensation. LDA is used as the base in the first step, and the final step of the process is aqueous acidic work-up, as shown: 21.27. (a) This is an example of an intramolecular Claisen Condensation (called a Dieckmann cyclization). The  position of one ester group is deprotonated, and the resulting enolate functions as a nucleophile and attacks the other carbonyl group within the same structure. As a result, a ring is formed, giving a tetrahedral intermediate. The carbonyl group is then reformed via loss of an ethoxide ion, giving a -ketoester: Under these basic conditions, the -ketoester is deprotonated to give a doubly-stabilized enolate, requiring acidic work-up in order to regenerate the - ketoester above. (b) This is an example of an intramolecular Claisen Condensation (called a Dieckmann cyclization). The  position of one ester group is deprotonated, and the resulting enolate functions as a nucleophile and attacks the other carbonyl group within the same structure. As a CHAPTER 21 853 result, a ring is formed, giving a tetrahedral intermediate. The carbonyl group is then reformed via loss of an ethoxide ion, giving a -ketoester: Under these basic conditions, the -ketoester is deprotonated to give a doubly-stabilized enolate, requiring acidic work-up in order to regenerate the - ketoester above. (c) This is an example of an intramolecular Claisen Condensation (called a Dieckmann cyclization). The  position of one ester group is deprotonated, and the resulting enolate functions as a nucleophile and attacks the other carbonyl group within the same structure. As a result, a ring is formed, giving a tetrahedral intermediate.

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