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From Tetrahedron Lett. 42:7983(2001)

Solvent free Claisen and Cannizzaro reactions

 
 
 
 
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I have the article sitting on my computer screen in either pdf or html but this is a public computer so I can't save to disk.  I'm not that good at puttin' up pictures on the hive neither (duh).  If this looks supa cool to you guys, then I'll send rhod the pdf from mi computadora en mi casa.  So here's all the script from the html w/o the pics.  Sorry...

Solvent-free Claisen and Cannizzaro reactions*1

Kazuhiro Yoshizawa, Shinji Toyota and Fumio Toda, 

Department of Chemistry, Okayama University of Science, Ridai-cho, Okayama 700-0005, Japan

Received 7 June 2001;  revised 16 July 2001;  accepted 21 August 2001.  Available online 25 September 2001.

 

Abstract

Claisen and Cannizzaro reactions were found to proceed efficiently under solvent-free conditions. The solvent-free Claisen reactions were especially effective for the
ester substituted with sterically bulky groups, which does not react in solution.

Graphical Abstract

Claisen and Cannizzaro reactions were found to proceed efficiently under solvent-free conditions.


Author Keywords: solvent-free reaction; Claisen reaction; Cannizzaro reaction; green chemistry
 

Article Outline

  Acknowledgements
  References


 

We have been studying how molecules move quite easily and even selectively in the solid state.1, (a), (b), (c), (d) and (e) When the molecular movements in the solid
state are applied to organic reactions, selective and efficient solvent-free organic reactions can be designed. 1, (a), (b), (c), (d) and (e) Recently, we found that the
title reactions also proceed efficiently under solvent-free conditions. In particular, the solvent-free Claisen reactions of the ester substituted with a sterically bulky
group proceeded very efficiently, although these reactions did not occur in solution. These solvent-free reactions are important not only for their efficiency and
simplicity, but also as green and sustainable procedures.

Claisen condensation reactions[2]

For example, after a mixture of ethyl acetate (1a) (3.52 g, 40 mmol) and powdered tBuOK (3.68 g, 28 mmol) was kept at 80C for 20 min, the reaction mixture
was neutralized by addition of dil. HCl and extracted with ether. The oil left after evaporation of the solvent from the dried ether solution was distilled in vacuo by
Kugelrohr apparatus to give 2a (1.9 g, 73% yield). When the same reaction was carried out in EtOH containing EtONa for 8 h under reflux, 2a was obtained in
3676% yield.3, (a) and (b) For example, when a solution of 1a (3.52 g, 40 mmol) and EtONa (1.9 g, 28 mmol) in EtOH (4 ml) was heated under reflux for 8 h,
2a (1.17 g, 45%) was obtained after the usual work up procedure.

The same treatment of 1b and 1c with tBuOK for 2 h and 10 min, respectively, gave 2b in 60% and 2c in 73% yields, respectively. In contrast, reactions of 1b and
1c in solution for 16 and 6 h, respectively, gave 2b and 2c in 47 and 55% yields, respectively.3, (a) and (b) These data clearly show that solvent-free reactions are
simpler and more efficient than solution reactions. For the ester substituted with a sterically bulky group, the difference in efficiency between solvent-free and solution
reactions becomes larger. Treatment of ethyl pentanoate (1d) with tBuOK for 1 h gave 2d in 61% yield, although its solution reaction for 32 h gave 2d in 35% yield.
Furthermore, solvent-free reaction of ethyl 3-methylbutanoate (1e) for 1 h gave 2e in 33% yield; however, solution reaction for 48 h did not give any 2e, and 1e
was recovered unchanged. A plausible explanation of the inefficiency of the reaction in solution is that the reactant and reagent are solvated and their mutual
approach to the condensation reaction becomes difficult for sterical reasons.

A similar steric effect was observed in the reaction of benzyl carboxylate (3). When 3ad were treated with tBuOK under solvent-free conditions at the reaction
temperature and reaction time indicated in Table 1, 4ad were obtained in the moderate yields shown in Table 1. When the same reactions of 3ae were carried out
in toluene and tBuOH under reflux for 16 h, no condensation product was obtained and 3ae were recovered unchanged. In solution reactions, exchange of the
alkoxy group occurs among the substrate, reagent and solvent. Therefore, the alkoxy groups of the ester, metal alkoxide and alcohol used as a solvent should be
identical. In the solvent-free reactions, however, a strong base such as tBuOK can be used for any kind of ester substrate, since such exchange does not occur. This
is also a considerable advantage (Scheme 1 and Scheme 2.

      

     Table 1. Solvent-free Claisen condensation reactions of 3
          (3K)




                       (3K)

     Scheme 1.




                       (3K)

     Scheme 2.



Cross-condensation reaction of benzyl benzoate (5) and benzyl carboxylate (6) was carried out under solvent-free conditions. Treatment of a 1:1 mixture of 5 and 6
with tBuOK under the conditions indicated in Table 2 gave the cross-condensed product 7 in the yield shown in Table 2. Although the cross-condensation between
5 and 6c did not occur, cross-condensation products 7a and 7b were obtained in moderate yields. Because heating of 5, 6 and tBuOK in toluene under reflux for
16 h did not give any product, it is clear that the solvent-free reaction is again effective even for the cross-condensation. In these cases, self-condensation of 6 itself
did not occur probably because of the high reactivity of 5 (Scheme 3).

Cannizzaro reactions[4]

      

     Table 2. Solvent-free cross-condensation reactions of 5 and 6
          (2K)




                       (4K)

     Scheme 3.



After a mixture of powdered 1-formylnaphthalene (8) (4.68 g, 30 mmol) and powdered KOH (2.52 g, 45 mmol) was kept at 100C for 5 min, water was added to
the reaction mixture, and was filtered to give 1-(hydroxymethyl)naphthalene (10), after Kugelrohr distillation, (0.485 g, 38% yield). The filtrate was acidified by
conc. HCl and filtered to give 1-naphthoic acid (9) (0.57 g, 41% yield). For liquid aldehydes, a similar method can be applied. When the alcohol formed by the
solvent-free reaction is an oily material, the product was extracted with ether. Finally, treatment of aldehydes 1118 by these procedures gave the corresponding
alcohols and acids in the yields indicated in Table 3.



     Table 3. Solvent-free Cannizzaro reactions
          (5K)



In the case of crystalline p-methylbenzaldehyde (16), the yield of p-methylbenzoic acid exceeded 50%, probably due to air oxidation of 16 during the reaction at
80C. When the reaction was carried out at room temperature in nitrogen atmosphere under ultrasound irradiation, p-methylbenzoic acid and p-methylbenzyl alcohol
were obtained in 43 and 33% yield, respectively (Table 3). In all cases shown in Table 3, solvent-free Cannizzaro reactions proceeded efficiently under milder
conditions, and the products were obtained in moderate yields by a simple separation method ( Scheme 4 and Scheme 5).



                       (3K)

     Scheme 4.




                       (6K)

     Scheme 5.



The solvent-free Cannizzaro reaction has some advantages. In addition to simplicity and cleanness of the procedure, the solvent-free reaction proceeds much faster
than a solution reaction. For example, reaction of 11 in 60% aq. KOH takes 24 h to complete,[5] although the solvent-free reaction is completed within 5 min. In all
other cases indicated in Table 3, all reactions are completed within 30 min.


Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan.


References

1. (a). F. Toda Synlett (1993), p. 302.
(b). F. Toda Acc. Chem. Res. 28 (1995), p. 480.
(c). F. Toda Supramol. Sci. 3 (1996), p. 139. Abstract | Journal Format-PDF (646 K)
(d). F. Toda Compr. Supramol. Chem. 6 (1996), p. 465.
(e). K. Tanaka and F. Toda Chem. Rev. 100 (2000), p. 1025. Full-text via CrossRef

2. C.R. Hauser and B.E. Hudson, Jr. Org. React. I (1942), p. 266.

3. (a). M.A. Spielman and M.T. Schmidt J. Am. Chem. Soc. 59 (1937), p. 2009.
(b). N. Fisher and S.M. Mcelvain J. Am. Chem. Soc. 56 (1934), p. 1766.

4. T.A. Geissman Org. React. II (1944), p. 94.

5. W.M. Cumming, I.V. Hopper and T.S. Wheeler Syst. Org. Chem. (1950), p. 190.


*1 This paper is dedicated to Professor Masazumi Nakagawa on the occasion of his 85th birthday.

   Corresponding author. Fax: +81 86 256 9604; email: toda@chem.ous.ac.jp


 Tetrahedron Letters
 Volume 42, Issue 45
 5 November 2001
 Pages 7983-7985

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Tetrahedron Letters 42 (2001) 7983-7985



Solvent-free Claisen and Cannizzaro reactions

Kazuhiro Yoshizawa, Shinji Toyota and Fumio Today
Department of Chemistry, Okayama University of Science. Ridai-cho. Okayama 700-0005, Japan


Abstract - Claisen and Cannizzaro reactions were found to proceed efficiently under solvent-free conditions. The solvent-free clausen reactions were especially effective for the ester substituted with statically bulky groups. which does not react in solution.
 

We have been studying how molecules move quite easily and even selectively in the solid state.1 When the molecular movements in the solid state are applied to organic reactions, selective and efficient solvent-free organic reactions can be designed.1 Recently, we found that the title reactions also proceed efficiently under solvent-free conditions. In particular, the solvent-free Claisen reactions of the ester substituted with a sterically bulky group proceeded very efficiently, although these reactions did not occur in solution. These solvent-free reactions are important not only for their efficiency and simplicity, but also as green and sustainable procedures.

Claisen condensation reactions2

For example, after a mixture of ethyl acetate (1a) (3.52 g. 40 mmol) and powdered tBuOK (3.68 g, 28 mmol) was kept at 80C for 20 min, the reaction mixture was neutralized by addition of dil. HCI and extracted with ether. The oil left after evaporation of the solvent from the dried ether solution was distilled in vacuo by Kugelrohr apparatus to give 2a (1.9 g, 73% yield). When the samc reaction was carried out in EtOH containing EtONa for 8 h under reflux, 2a was obtained in 36-76% yield.3 For example, when a solution of la (3.52 g, 40 mmol) and EtONa (1.9 g, 28 mmol) in EtOH (4 m1) was heated under reflux for 8 h, 2a (1.17 g, 45%) was obtained after the usual work up procedure.

The same treatment of 1b and 1c with tBuOK for 2 h and 10 min, respectively, gave 2b in 60% and 2c in 73% yields, respectively. In contrast, reactions of 1b and 1c in solution for 16 and 6 h, respectively, gave 2b and 2c in 47 and 55% yields, respectively. 3 These data clearly show that solvent-free reactions are simpler and more efficient than solution reactions. For the ester substituted with a sterically bulky group, the difference in efficiency between solvent-free and solution reactions becomes larger. Treatment of ethyl pentanoate (1d) with tBuOK for 1 h gave 2d in 61% yield, although its solution reaction for 32 h gave 2d in 35% yield. Furthermore, solvent-free reaction of ethyl 3-methylbutanoate (1e) for 1 h gave 2e in 33% yield; however, solution reaction for 48 h did not give any 2e, and 1e was recovered unchanged. A plausible explanation of the inefficiency of the reaction in solution is that the reactant and reagent are solvated and their mutual approach to the condensation reaction becomes difficult for sterical reasons.

A similar steric effect was observed in the reaction of benzyl carboxylate (3). When 3a-d were treated with tBuOK under solvent-free conditions at the reaction temperature and reaction time indicated in Table 1, 4a-d were obtained in the moderate yields shown in Table l. When the same reactions of 3a-e were carried out in toluene and tBuOH under reflux for 16 h, no condensation product was obtained and 3a-e were recovered unchanged. In solution reactions, exchange of the alkoxy group occurs among the substrate, reagent and solvent. Therefore, the alkoxy groups of the ester, metal alkoxide and alcohol used as a solvent should be identical. In the solvent-free reactions, however, a strong base such as tBuOK can be used for any kind of ester substrate, since such exchange does not occur. This is also a considerable advantage (Schemes 1 and 2).

Cross-condensation reaction of benzyl benzoate (5) and benzyl carboxylate (6) was carried out under solvent-free conditions. Treatment of a 1:1 mixture of 5 and 6 with tBuOK under the conditions indicated in Table 2 gave the cross-condensed product 7 in the yield shown in Table 2. Although the cross-condensation between 5 and 6c did not occur, cross-condensation products 7a and 7b were obtained in moderate yields. Because heating of 5, 6 and tBuOK in toluene under reflux for 16 h did not give any product, it is clear that the solvent-free reaction is again effective even for the cross-condensation. In these cases, self-condensation of 6 itself did not occur probably because of the high reactivity of 5 (Scheme 3).

Cannizzaro reactions4

After a mixture of powdered l-formylnaphthalene (8) (4.68 g, 30 mmol) and powdered KOH (2.52 g, 45 mmol) was kept at 100C for 5 min, water was added to the reaction mixture, and was filtered to give l-(hydroxy-methyl)naphthalene (10), after Kugelrohr distillation, (0.485 g, 38% yield). The filtrate was acidified by conc. HCl and filtered to give l-naphthoic acid (9) (0.57 g, 41% yield). For liquid aldehydes, a similar method can be applied. When the alcohol formed by the solvent-free reaction is an oily material, the product was extracted with ether. Finally, treatment of aldehydes 11-18 by these procedures gave the corresponding alcohols and acids in the yields indicated in Table 3.

In the case of crystalline p-methylbenzaldehyde (16), the yield of p-methylbenzoic acid exceeded 50%, probably due to air oxidation of 16 during the reaction at 80C. When the reaction was carried out at room temperature in nitrogen atmosphere under ultrasound irradiation, p-methylbenzoic acid and p-methylbenzyl alcohol were obtained in 43 and 33% yield, respectively (Table 3). In all cases shown in Table 3, solvent-free Cannizzaro reactions proceeded efficiently under milder conditions, and the products were obtained in moderate yields by a simple separation method (Schemes 4 and 5).

The solvent-free Cannizzaro reaction has some advantages. In addition to simplicity and cleanness of the procedure, the solvent-free reaction proceeds much faster than a solution reaction. For example, reaction of 11 in 60% aq. KOH takes 24 h to complete, 5 although the solvent-free reaction is completed within 5 min. In all other cases indicated in Table 3, all reactions are completed within 30 min.

References

1 . (a) Toda, F. Synlett 1993, 302; (b) Toda, F. Acc. Chem. Res. 1995, 28, 480; (c) Toda, F. Supramol. Sci. 1996, 3, 139; (d) Toda, F. Compr. Supramol. Chem. 1996. 6, 465; (e) Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
2. Hauser, C. R.; Hudson, Jr., B. E. Org. React. 1942, 1, 266.
3. (a) Spielman, M. A.; Schmidt, M. T. J. Am. Chem. Soc. 1937, 59, 2009; (b) Fisher, N.; Mcelvain, S. M. J. Am. Chem. Soc. 1934, 56, 1766.
4. Geissman, T. A. Org. React. 1944, II, 94.
5. Cumming, W. M.; Hopper, I. V.; Wheeler, T. S. Syst. Org. Chem. 1950, 190.