Ionic Liquids in Organic Synthesis - American Chemical Society

Chapter 8

Approaches to Imino Diels-Alder Reactions in Imidazolium Ionic Liquids

Downloaded by COLUMBIA UNIV on August 6, 2012 | http://pubs.acs.org Publication Date: January 18, 2007 | doi: 10.1021/bk-2007-0950.ch008

Richard Kim, Ildiko Meracz, Laura Serbulea, Geronimo Cebero, and Taeboem Oh* Department of Chemistry, California State University at Northridge, 18111 Nordhoff Street, Northridge, CA 91330-8262

Abstract: Imino Diels-Alder reactions can be carried out in imidazolium ionic liquids. Depending on the design of the ionic liquid, it may or may not require Lewis acid activation. Several new chiral and achiral imidazolium compounds have been synthesized, but they had melting points above room temperature.

Introduction The recent interest in ionic liquids and use of ionic liquids in organic reactions is overwhelming (1-7). Our interest in the area grew from the possibility that ionic liquids might improve the Diels-Alder reactions for synthesis (8). We present our work in ionic liquids related to imino Diels-Alder reactions (9, 10). As our entry into this field, we have chosen the imidazolium ionic liquids (Figure 1) (11,12). We have chosen dialkylimidazolium, methylbutyl-imidazolium (MeBuIm) 1 and Dibutylimidazolium (DiBuIm) 2 compounds. For reasons that will be discussed later we considered imidazolium ionic liquids, which have an NH-functional group. Specifically, we chose hydrogenbutylimidazolium (HBuIm) 3 and hydrogenbenzylimidazolium (HBnIm) 4. For chiral imidazolium ionic liquids, we have chosen (S)hydrogenmethylbenzyl-imidazolium (HMeBnIm) 5, (S)methylmethylbenzylimidazolium (MeMeBnIm) 6, and (S, S)-dimethylbenzylimidazolium (DiMeBnIm) 7 ionic compounds were selected. © 2007 American Chemical Society

In Ionic Liquids in Organic Synthesis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2007.

95

96 Dialkylimidazolium compound

1, MeBulm

2, DiBulm

Hydrogenalkylimidazolium compound


X"

3, HBulm

4, HBnlm

Chiral imidazolium compound X

CH3

CH3

X

CH3 X "

w

J

5, HMeBnlm

N^N

\=J

w

6, MeMeBnlm

CH3

7, DiMeBnlm

Figure 1. Imidazolium compounds of interest.

We examined the simple imino Diels-Alder reactions of Danishefsky's diene 8 (R=Me Si) and benzylimine of benzaldehyde 9 (Eq 1). The results are tabulated in Table 1. For a reference point, we attempted the reaction in dioxane, dichloromethane, and ethylacetate to confirm that the cycloaddition did not occur in our hands. However, in dialkylimidazolium salts, the reaction undergoes cycloaddition. The cycloaddition of Danifesky's diene and benzylidinebenzylamine in MeBulm gave lower yields then in DiBulm salts (entries 4, 5, 6). Monitoring the reaction by NMR and GC show that there is a significant decomposition of the diene. When the reaction comes to a stop, imine still remains but no diene. To increase the stability of the diene, Danifshesky's diene was replaced with the TBS analog, which gave better yields. Using HBulm increased the rate of the destruction of the diene and low yields of the cycloadduct were produced (entries 10 and 11). A combination of HBulm and DiBulm was attempted to increase the rate of the cycloaddition (entries 12-14). Only a small percentage of HBulm was needed to affect the rate (entries 10 and 11). Using 10% of HBulm gave lower yield probably due to the destruction of the diene. 3


97 CH 0 3

+ R

0

jl

^

PiT

8

9

Reaction Conditions

t

J

τ

0 ^ " S h

10

Table 1. Imino Diels-Alder reactions of 8 and 9.


Entry

1

1

TBS

Eq Conc Time Yield Diene (M) (%) (h) 1.4 0.8 0 12

2

CH C1

2

TBS

1.0

1.0

12

0

3

EtOAc

TBS

1.0

1.1

12

0

4

MeBulm

TMS

1.3

0.3

48

21

5

DiBulm

TMS

1.8

2.0

37.5

43

6

DiBuIm

TMS

2.9

2.0

21.5

59

7

DiBulm

TBS

1.0

4.2

18

62

8

DiBulm

TBS

1.2

2.5

16

65

9

DiBulm

TBS

1.6

1.9

16

57

10

HBulm

TMS

1.0

1.0

12

16

11

HBulm

TMS

1.5

0.3

12

19

12

10% HbuIm/DiBuIm/BF

4

TMS

3.7

2.0

23

47

13

1.5% HbuIm/DiBuIm/BF

4

TMS

1.2

2.0

5

55

14

1.5% HbuIm/DiBuIm/BF

4

TMS

3.4

2.0

23

60

2

R

1

Reaction Conditions Dioxane

TBS=/-butyldimethylsilyl, TMS=trimethylsilyl

To be sure that no trace of tetrafluoroboric acid contaminant was catalyzing the cycloaddition, a solution of DiBuImBF in dichloromethane was treated with potassium carbonate, Dowex 66, or both. The resulting ionic liquid still showed product. But unexpectedly, in the presence of one or two equivalents of triethylamine, the cycloaddition did not proceed. This interesting turn of events, led us to investigate this reaction in the presence of basic additives and other counter ions. Table 2 summarizes the results using the TBS diene and benzylidinebenzylamine dienophile. 4


98 Table 2. Imino Diels Alder reactions. Entry

Reaction conditions B u . ^ + Bu Pre-treatedwithK C0 ^ ^ and/or Dowex 66 N

1

2

N

χ·

Con

BF "

76

BF "

0

BF "

0

4

4

3

B

U

^ N '

B

U

w

4

B U

+

N^N'

B

2

3

N

2


1

U

4

w

^N^N'

0

CF C0 "

B U

3

2

V=/ BF " 4

5

HN^N'

B U

68

lEqEtjN

V=/ BF " 4

6

πι

^

HN^N'

7

2

ρ

1 eq 1-butylimidazole

50 N0 ' 3

B U

42

For the purpose of these studies, these reactions have not been optimized. Conversion as determined by the ratio of starting material and product by *H NMR.

The removal of the Bronsted acid indicates that it is not involved in the cycloaddition (entry 1). Presence of either triethylamine or butylimidazole prevents the reaction (entries 2 and 3). Replacement of the BF counterion with trifluoroacetate also prevents the cycloaddition. *H-NMR of benzaldehyde in DiBuImBF shows two distinct aldehyde hydrogen resonances (Figure 2). The minor downfield shift of the aldehyde resonance is typical of Lewis acid coordinated aldehydes. The only potential Lewis acid present is BF . The ionic liquid may be facilitating the formation of BF from BF (Eq 2). The presence of small amounts of fluoride ion may account for the destruction of the silyloxy diene. It's interesting to note that HBulm can catalyze the reaction in the 4

4

3

3

4


99 presence of base with counterion B F , or C F C 0 , or N 0 , indicating that N-H can form a strong enough hydrogen bond with the substrate to catalyze the reaction (entries 5, 6, and 7).


4

10

V.5

V.O

3

8.5

2

3

8.0

7.5

Figure 2. a) *HNMR spectra ofbenzaldehyde in BiBuImBF . b) Blow up of the aldehyde region. 4

The fact that dialkylimidazolium needs Lewis acid to catalyze the imino Diels-Alder reactions while the hydrogenalkylimidazolium salts give a more reactive condition confirms our thoughts. It is known that dialkylimidazolium salts can activate carbonyls through hydrogen bonding (Figure 3, complex 11) (13). The HBulm ionic liquid with the hydrogen bond to the charged nitrogen


100

R

X

J

R ^ R

11

12


Figure 3. Hydrogen bonding by dialkyl and hydrongenalkyl imidazolium compounds.

should induce a more reactive condition through a stronger hydrogen bond (complex 12). We examined the properties of dibenzylimidzolium derivatives. Symmetrical derivatives were synthesized by known methods (Eq 3 and Table 3) (14,15). In all cases, the imidazolium compounds were solids at room temperature. Dissymmetrical versions were synthesized by similar methods (Figure 4, Table 4). In this case, most were also solids at room temperature (entries 6-10).

(3) 13

14 Table 3. Symmetrical dibenzylimidazolium salts. M.p. rangefC)

Entry

R

χ-

1

Η

BF

4

85-87

2

Η

N0

3

64-67

3

Η

Camphor Sulfonate

68-72

4

Η

CF C0

71-73

5

OCH

3

BF

4

131-135

6

OCHj

N0

3

169-170

7

CI

BF

4

94-96

S

CI

N0

3

123-129

9

CI

Camphor Sulfonate

3

2

156-160


101

Table 4. Melting points of desymmetrical imidazolium salts. Entry

R'

1

Ph^^

R

Λ

χ·

2

/

CH 2

Ionic Liquids in Organic Synthesis - American Chemical Society

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