Ionic Liquids in Organic Synthesis - American Chemical Society

Chapter 5

Diels-Alder and Friedel-Crafts Reactions in Pyridinium-Based Ionic Liquids Downloaded by NORTH CAROLINA STATE UNIV on August 7, 2012 | http://pubs.acs.org Publication Date: January 18, 2007 | doi: 10.1021/bk-2007-0950.ch005

Sanjay V. Malhotra and Ying Xiao Department of Chemistry and Environmental Science, New Jersey Institute of Technology, University Heights, Newark, NJ 07102

Diels-Alder and Friedel-Crafts reactions have been investigated in pyridinium based ionic liquids (ILs). Various factors such as reaction temperature, reaction time, reactant, catalyst-IL composition, catalyst dosage were studied. The reactions were found to proceed under relatively mild conditions with good overall conversion. The ILs are found to be more effective compared to the organic solvents in enhancing the reaction rate and product yield. Also, the ILs could be recycled and reused efficiently.

Introduction Recently, ionic liquids (ILs) have gained a lot of attention as green solvents in organic reactions (7) and other chemical processes (2). The increased interest for their investigations is mainly due to their favorable properties, such as chemical and thermal stability, negligible vapor pressure, non-flammability, high ionic conductivity, high polarity, ease to recycle (J). Also they are strongly solvating but non-coordinating; could have profound effect on the activity and selectivity of reactions and in some cases, facilitate the isolation of products. Therefore, ILs are considered as viable substitutes for volatile organic solvents. 58

© 2007 American Chemical Society

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

Downloaded by NORTH CAROLINA STATE UNIV on August 7, 2012 | http://pubs.acs.org Publication Date: January 18, 2007 | doi: 10.1021/bk-2007-0950.ch005

59 There are literature examples reporting clean synthesis and improved reaction characteristics in ILs. They have been investigated as reaction media in many organic and organometallic syntheses such as hydrogenation (4), oxidation (5), Diels-Alder reaction (6), Heck reactions (7), Friedel-Crafts reactions, (8) Trost-Tsuji coupling (9), esterification (70), Beckman rearrangement (77). As highly ordered media with environmentally friendly properties, ILs have the potential to influence the outcome of the reactions. All these studies have focused on solvents derived from imidazole. However, pyridinium based ILs also have favorable properties and could be important reaction media for organic transformations. Herein we report our investigation of Diels-Alder and FriedelCrafts alkylation and alcylation in pyridinium base ILs.

Pyridinium Based Ionic liquids Two pyridinium based ILs 1-ethyl-pyridinium trifluoroacetate ([EtPy] [CF COO]') and 1-ethyl-pyridinium tetrafluoroborate ([EtPy] [BF ]') were studied. The preparation procedure (72) are modified based on the literature methods. (75) +

+

3

4

+

[EtPy] [CF COO]" 3

A

+

[EtPy] [BF ] 4

Β

Scheme 7. Pyridinium based ionic liquids

Diels-Alder Reaction The Diels-Alder reaction is one of the most important tools for carboncarbon bond formation. It is a widely used reaction in organic synthesis and in the chemical industry (14). The reaction has been investigated using water (75), surfactants (16), lithium amides (77), borane-THF complex (18) and imidazolium based ILs (6). We investigated the reactions of isoprene 1 with acrylonitrile 2, acrylic acid 3 and methacrylic acid 4 (Scheme 2) in [EtPy] [BF ]" and [EtPy] [CF COO]-(19). In a typical reaction, the molar ratio of isoprene: dienophile: IL is 1.5:1:1. All reactions are heterogeneous in nature. The major products are 'para like' (5, 7, 9). The results are shown in Table 1. +

4

+

3



60

Scheme 2. Diels-Alder reactions of isoprene with different dienophiles

Table 1. Diels-Alder reactions at 20 °C Entry

Solvent

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

CH C1 Phosphonium tosylates [EtPyl rBF V [EtPy] rBF V [EtPy] [CF COO][EtPy] [CF COO]CH C1 Borane-THF + CH C1 [EtPy] [BF T [EtPy] [BF l[EtPy] [CF COO][EtPy] [CF COO]' CH C1 Borane-THF + CH C1 [EtPy] [BF y [EtPy] [BF ]" [EtPy] [CF COOV [EtPy] [CF COO]2

C

2

+

4

+

4

+

3

+

3

2

e

2

2

2

+

4

+

4

+

3

+

3

2

f

2

2

+

4

+

4

+

3

+

3

a

b

2

Time (h) 72 24 2(24) 72 2(24) 72 72 30 2(24) 72 2(24) 72 72 68 24 72 2(24) 72

Dieno -phile 2 2 2 2 2 2 3 3 3 3 3 3 4 4 4 4 4 4 c

a

Yield (%) 12 38 42 (64) 83 90 (97) 99 27 75 32 (50) 55 97 (98) 98 5 66 18 22 55 (64) 67

Selectivity

b

64:36 69:31" 84:16" (66:34) 58:42 89:11" (75:25) 75:25 70:30 • -

82:18" (65:35) 62:38 95:5" (85:15) 80:20 58:42

66:34 55:45" 62:38 (54:46) 1:1"

d

Determined by GC; "para like": "meta like"; Ref. 20, 80°C; Ratio determined by *H NMR; Ref 18, 0°C; Ref. 18. e

f


61 The reaction rate and yields are found to be dependent on the solvent used. The reaction of isoprene with acrylonitrile 2 in CH C1 gave very low yield after 72 hours (entry 1). While the same reaction when carried out in [EtPy]*[BF ]" gave 42% yield (entry 3). The reaction seems to slow down there after as we see only 64% in 24 hours and 83% after 72 hours. This reaction also proceeds much faster compared to phosphonium tosylates solvent where even at 80 °C only 38% yield is seen after 24 hours, (ref 23) Reaction in [EtPy] [CF COO]" proceeds at a much faster rate resulting in 90% yield in 2 hours. In all cases, however, as the reaction is continued beyond 2 hours there is a decrease in 'para/meta like' product ratio, while overall yield of the combined products increased. Similar results are also seen in reaction of isoprene with acrylic acid 3 (entries 7-12) and methacrylic acid 4 (entries 13-18). As electron-withdrawing substituents, -COOH and -CN make C-2 more active than C-l in LUMO of dienophile; whereas electron-releasing substituent, CH makes C-l more active than C-4 in HOMO of isoprene. Therefore, the 'para like' products are predominant over 'meta like' products. The varied effect on the rate could be attributed to the difference in coordination of cation and anion in these two solvents (Scheme 1). As Lewis acids, ILs may form complex with the substituent (-COOH or -CN) on dienophiles, which increases the electronwithdrawing capacity of the substituent group, lowers both the energy and orbital of dienophile, thus lowering the reaction activation energy and enhancing both the reactivity and selectivity of the reaction. On the other hand, as high polar solvents, ILs could facilitate the reaction between diene and dienophile, therefore the reaction occurs not only faster but more efficiently than the tranditional organic solvent. In a word, the interaction between dienophile and IL increases the coefficient of C-2 in LUMO of dienophile and make it more efficient to react with C-l in HOMO of isoprene as shown in Scheme 3. 2

2

4

+


3

3

Scheme 3. The mechanism of Diels-Alder reactions

Due to its electron-donating effect, the methyl group offsets the electron withdrawing effect of the carboxyl group on dienophile, and raises the dienophile orbitals, thus making the methacrylic acid relatively less active than acrylic acid. Therefore, both overall yields and selectivities are lower than those of acrylic acid. With a decrease in temperature to 0 °C, the selectivity increased slightly, and the overall yield can be kept the same by the prolonged reaction


62 time. On the other hand at 45 °C the rate of reaction is accelerated, but selectivity to main product dropped significantly to 50-56%. It is also important to note that at 0 °C and 20 °C, the reactions mixtures were in heterogeneous, however increasing the reaction temperature to 45 °C gave a homogeneous mixture. The reusability of IL was studied by successive runs performed with the recovered [EtPy] [CF COO]' for reaction between isoprene and acrylonitrile (Scheme 2, equation 1) at 20 °C for 24 h. The IL could be recovered quantitatively (about 96% yield) and without loss of activity, which is evident from the fact that the overall product yield is not affected even after six runs (92% yield). +


3

Friedel-Crafts Alkylation and Acylation Friedel-Crafts chemistry is important both on laboratory and industrial scale. (21) Traditionally, this reaction can be promoted by Lewis acids, such as BF , ZnCl , TiCl , SbF etc, though aluminium chloride is mostly used as catalyst. However, it has some disadvantages, such as long reaction time, troublesome product recovery and purification, catalysts can not be reused and formation of environmentally hazardous, corrosive aluminate waste. In contrast, very few examples are reported in the literature where FeCl , an environmentally favorable catalyst has been used (22). A general mechanism of Friedel-Crafts reaction is shown in Scheme 4 (23). Herein, R- group could be alkyl group for alkyaltion, or carbonyl group for acylation. 3

2

4

5

3

+ (1) R—X + Lewis Acid < +

R -X-Lewis~Acid «.

*

R—X—Lewis Acid

»

R + [ Lewis Acid—X ]"

+

Scheme 4. General Mechanism ofAlkylation and Acylation Alkylation Alkylation of benzene 1 with 2, 3 & 4 is shown in scheme 5 (24).


63


Scheme 5. Friedel-Crafts Alkylation Reactions of Benzene

Both 'iso-' (5) and 'η-' product (6) were obtained in alkylation of benzene and 1-bromopropane. The reaction proceeds via formation of either a carbocation or an acylium ion or a polarized complexes that still contain the leaving group, which is often accompanied by rearrangement of the alkylating group, i.e. The primary propyl cation undergoes a hydride shift to form the more stable isopropyl cation, therefore isoropylbenzene is major product.

Table 2. Friedel-Crafts alkylation of Benzene Conv.(%) rt(50°C) 1 2 17(43) [EtPy] [BF ]2 2 [EtPy] [CF COO]29 (51) 3 2 60 (81) AlCl -[EtPy] [BF ]" 4 2 AlCl -[EtPy] [CF COO]72(91) 5 2 FeCl -[EtPy] [BF ]56 (80) 71 (90) 6 2 FeCl -[EtPy] [CF COO]rEtPy] rBF ]7 3 21 (45) 8 3 [EtPy] [CF COO]34(55) AlCl -[EtPy] [BF ]9 3 68 (87) AlCl -[EtPy] [CF COO]77 (96) 10 3 11 FeCl -[EtPy] [BF ]67 (88) 3 12 FeCl -[EtPy] [CF COO]77 (94) 3 iEtPyl rBF ]4 13

Ionic Liquids in Organic Synthesis - American Chemical Society

Recommend Documents