Recyclable Organomolybdenum Lewis Acid Catalyst and Microwave Assisted Pechmann Condensation Reactions

1
Recyclable Organomolybdenum Lewis Acid Catalyst
and Microwave Assisted Pechmann Condensation
Reactions

• Student Chia-Pei Chung Supervisor Prof.
  Shuchun Joyce Yu
• 2006 / 07 / 20
• Department of Chemistry Biochemistry
• Chung Cheng University

2
Pechmann Condensation

• The Pechmann condensation is a synthesis of
  coumarins, starting from a phenol and a ester or
  carboxylic acid containing a ß-carbonyl group.
• Coumarin synthesis

Woodruff, E. H. Organic Syntheses, 1944, 24,
69. Pechmann, H. V. Duisberg, C. Ber. 1883, 16,
2119.
3
Coumarins

• present in seeds, root, and leaves of many plant
  species
• As additives to food and cosmetics, optical
  brightening agents, and dispersed fluorescent and
  laser dyes
• has clinical value as the precursor for several
  anticoagulants, antibacterial, anticancer
• can be synthesized by one of such methods as the
  Claisen rearrangement, Perkin reaction,
  Knoevenagel condensation, Reformatsky reaction,
  Wittig reactions, as well as the Pechmann
  Condensation reaction

4
Acidic Catalysts for Pechmann Condensation

• Proton Donor Brønsted Acids
• H2SO4, HCl, TFA (trifluoroacetic acid)
• Pechmann V. H. Duisberg C. Chem. Ber. 1884, 17,
  929.
• Woods, L. L. Sapp, J. J. Org. Chem. 1962, 27,
  3703.
• Traditional Lewis Acid Catalysts
• InCl3, AlCl3, BiCl3, FeCl3, TiCl4, ZrCl4, P2O5,
  PCl3, POCl3
• Bose, D. S. Rudradas, A. P. Babu, M. H.
  Tetrahedron Lett. 2002, 43, 9195.
• S. K. De, R. A. Gibbs, Synthesis, 2005, 1231.
• Simmonis, H. Remmert, P. Chem. Ber. 1914, 47,
  2229.
• Robertson, A. Sandrock, W. F. Henry, C. B. J.
  Chem. Soc. 1931, 2426.

5
Acidic Catalysts for Pechmann
Condensation -- continued

• Lanthanide Lewis Acid Catalysts
• Yb(III), Sm(III)
• Fillion, E. et. al. J. Org. Chem. 2006, 71, 409.
• Bahekar, S. S. Shinde, D. B. Tetrahedron Lett.
  2004, 45, 7999.
• Others
• graphite / montmorillonite K10
• Amberlyst-15, Nafion
• Heteropoly acid (H6P2W18O62.24H2O)
• Frere, S. Thiery, V. Besson, T. Tetrahedron
  Lett. 2001, 42, 2791.
• Sabou, R. Hoelderich, W. F. Ramprasad, D.
  Weinand, R. J. Catal. 2005, 232, 34.
• Laufer, M. C. Hausmann, H. Hölderich, W. F. J.
  Catal. 2003, 218, 315.
• Autino, J. C. et. al. Tetrahedron Lett. 2004, 45,
  8935.

6
TFA Catalyzed Pechmann Condensation
Phenol used Phloroglucinol, 2-Methylresorcinol,
Resorcinol, Orcinol,
4-Chlororesorcinol, Pyrogallol, 3-Hydroxydiphenyl
amine ß-carbonyl esters used Ethyl benzoyl
acetate
Woods, L. L. Sapp, J. J. Org. Chem. 1962, 27,
3703.
7
Indium(III) Chloride Catalyzed Pechmann
Condensation
Phenol used Resorcinol, Orcinol, 4-, Pyrogallol,
3-Hydroxydiphenyl amine,
3-methoxyphenol, 1,3,5-trihydroxybenzene, phenol,
1-naphthol
Bose, D. S. Rudradas, A. P. Babu, M. H.
Tetrahedron Lett. 2002, 43, 9195.
8
POCl3 Catalyzed Pechmann Condensation
in Neutral Ionic
Liquids
Phenol used Resorcinol, 2-Methylresorcinol,
Orcinol, Pyrogallol,
1,3,5-trihydroxybenzene, 2',4'-Dihydroxyacetopheno
ne
Potdar, M. K. Rasalkar, M. S. Mohile, S. S.
Salunkhe, M. M. J. Mol. Catal. A Chem. 2005, 235,
249.
9
Yb(OTf)3 Catalyzed Pechmann Condensation
Phenol used 3,5-dimethoxyphenol,
3,4-dimethoxyphenol, sesamol,
3-methoxy-2-methylphenol
Fillion, E. et. al. J. Org. Chem. 2006, 71, 409.
10
Microwave acceleration of the Pechmann reaction
on graphite/montmorillonite K10
Experimental conditions Conventional heating Conventional heating Microwave irradiation Microwave irradiation
Experimental conditions Reaction time (min) Yield () Reaction time (min) Yield ()
Neat (fusion) 120 36 85 39
Support graphite 120 44 50 44
Support graphiteK10 (21)a, b 66 64 30 66
a. No modifications were observed when a
preliminary activation (2 h at 180C) of the clay
was realized. b. No significant results were
observed in the absence of graphite
(montmorillonite K10 phenol b-ketoester).
Frere, S. Thiery, V. Besson, T. Tetrahedron
Lett. 2001, 42, 2791.
11
WellsDawson heteropolyacid Catalyzed
Pechmann Condensation
Phenol used resorcinol, phloroglucinol,
3-methoxyphenol, pyrogallol,
3,4-dimethylphenol, 3-methylphenol, orcinol,
1-naphthol
Romanelli,G. P. Bennardi, D. Ruiz, D. M.
Baronetti, G. Thomas, H. J. Autino, J.
C. Tetrahedron Lett. 2004, 45, 8935.
12
Synthesis of Coumarins by Grubbs Catalyst
Van, T. N. Debenedetti, S. Kimpe, N. D.
Tetrahedron Lett. 2003, 44, 4199.
13
Disadvantages of Brønsted Acids

• Proton Donor Brønsted Acids
• Catalysts have to be used in excess, for example
  sulfuric acid, 1012 equiv, trifluoroacetic acid,
  34 equiv.
• Longer reaction time and very often temperatures
  to be excess 150 oC and above.
• Their corrosive nature and the formation of
  several side products make them difficult to
  handle.
• The disposal of acidic waste leads to
  environmental pollution.

14
Disadvantages of Traditional and Lanthanide
Lewis Acid

• Traditional Lewis Acid Catalysts
• Many chlorinated derivatives are highly moisture
  sensitive and hydrolyse rapidly under
  conventional storage or standard reaction
  conditions.
• The disposal of acidic waste leads to
  environmental pollution.
• Can not control electronic and steric
  environments around metal Lewis acid center.
• Lanthanide Lewis Acid Catalysts
• Lanthanide metals are relatively rare.

15
Motivation

• Low Oxidation State Transition Metals
• Relatively high moisture and oxygen stability
  
• Inexpensive
• Tunable electronic and steric environments around
  metal center
• Green Chemistry
• Greener solvents
• R.T. ionic liquids, BmimPF6
• Energy saving
• Catalysis under microwave flash
  heating
• replace thermal heating
• Recyclable catalyst

16
Preparation of Organomolybdenum Catalyst

• Thermal conditions

17
Crotonaldehyde-Lewis Acid Adduct
1H chemical shift H1 H2 H3 H4
crotonaldehyde crotonaldehyde Cat. 9.41 6.08 7.01 2.03 9.89 6.71 8.14 2.32
Chemical shift diff. 0.48 0.63 1.13 0.29
Childs, R. F. et. al. Can. J. Chem. 1982, 60, 801.
18
Lewis acid ?d on H3 (ppm)
BBr3 1.49
AlCl3 1.23
OP(2-Py)3W(CO)(NO)2(SbF6)2 1.23
OP(2-Py)3W(CO)(NO)2(BF4)2 1.22
P(2-Py)3W(CO)(NO)2(SbF6)2 1.21
HOC(2-Py)3W(CO)(NO)2(SbF6)2 1.19
P(2-Py)3W(CO)(NO)2(BF4)2 1.18
BF3 1.17
AlEtCl2 1.15
OP(2-Py)3Mo(CO)(NO)2(BF4)2 1.13
HC(2-Py)3Mo(CO)(NO)2(SbF6)2 1.05
TiCl4 1.03
P(2-Py)3Mo(CO)(NO)2(BF4)2 0.99
Me3P(CO)3(NO)W 0.93
SnCl4 0.87
CpMo(CO)2(PF6) 0.70
Et3Al 0.63
CpFe(CO)2BF4 0.54
19
Spectral Data of CO Coordinated Catalysts
Organometallic compound chemical shift (13C NMR) IR absorption band
OP(2-py)3W(CO)(NO)2(BF4)2 190.5 ppm 2156 cm-1/ nujol
P(2-py)3W(CO)(NO)2(SbF6)2 192.0 ppm 2143 cm-1/ nujol
P(2-py)3W(CO)(NO)2(BF4)2 192.2 ppm 2148 cm-1/KBr
Vapor CO 2143 cm-1
Mo(CO)6 202.3 ppm 2115,1983 cm-1/nujol
W(CO)6 192.1 ppm 2110,1980 cm-1/KBr
OP(2-py)3Mo(CO)(NO)2(BF4)2 223.0 ppm 2060 cm-1/KBr
P(2-py)3Mo(CO)(NO)2(BF4)2 222.0 ppm 2046cm-1/KBr
OP(2-py)3Mo(CO)3 227.5 ppm 1910,1806 cm-1/nujol
P(2-py)3Mo(CO)3 227.3 ppm 1908,1797cm-1/CD3Cl
OP(2-py)3W(CO)3 222.1 ppm 1890 cm-1/ nujol
P(2-py)3W(CO)3 222.9 ppm 1880,1762 cm-1/KBr
20
Organomolybdenum Lewis Acid Catalyzed
Pechmann
Condensation

• Thermal conditions

Solvent system bmimPF6 or CH3CN or DMF or
CH3NO2 or THF
21
Ionic Liquids
Seddon, K. R. et. al. Pure Appl. Chem. 2000, 72,
2275.
22
Coordinative Characteristics of Various Anions
Wasserscheid, P., et. al. Angew. Chem. Int. Ed.
2000, 39, 3772.
23
Room temperature ionic liquids exhibit many
properties which make them potentially attractive
media for homogeneous catalysis

• They have essentially no vapour pressure.
• They generally have reasonable thermal stability.
• They are able to dissolve a wide range of
  organic, inorganic and organometallic compounds.
• The solubility of gases.
• They are immiscible with some organic solvents.
• Ionic liquids have been referred to as designer
  solvents by a suitable choice of cation / anion.

24
Entry Phenol Yield () Entry Phenol Yield () Entry Phenol Yield ()
1 n. d. 6 n. d. 11 n. d.
2 n. d. 7 n. d. 12 n. d.
3 n. d. 8 n. d. 13 n. d.
4 n. d. 9 n. d.
5 n. d. 10 n. d.
25
Entry Phenol Time Yield () Entry Phenol Time (h) Yield ()
1 1 h 98 8 10 h 82
2 25 min 80 9 4 h 84
3 15 min 75 10 24 h 81
4 15 min 69 11 24 h n. d.
5 4 h 69 12 24 h n. d.
6 10 h 93 13 24 h n. d.
7 5 h 91
26
Entry Phenol Time Yield () Yield () Yield () Yield () Yield ()
Entry Phenol Time BmimPF6 CH3NO2 THF CH3CN DMF
1 1 h 91 64 32 9 n. d.
2 24 h -- 86 54 24 3
3 25 min 84 (20 min) 12 5 4 n. d.
4 7 h -- 82 42 (68) 40 (69) n. d. (5)
5 15 min 82 (10 min) 19 12 13 n. d.
6 2 h -- 83 81 82 12 (79)
After reacting 24 h, the products yield
27
Entry Phenol Time Yield () Yield () Yield () Yield () Yield ()
Entry Phenol Time BmimPF6 CH3NO2 THF CH3CN DMF
7 15 min 84 21 18 16 n. d.
8 2 h -- 82 80 80 n. d. (5)
9 4 h 82 (20 min) 22 10 n. d. n. d.
10 24 h -- 60 26 5 n. d.
After reacting 24 h, the products yield
28
Entry Phenol Time Yield () Yield () Yield () Yield () Yield ()
Entry Phenol Time BmimPF6 CH3NO2 THF CH3CN DMF
11 10 h 92 (6 h) 31 21 6 n. d.
12 24 h -- 54 40 12 n. d.
13 5 h 93 (1 h) 43 14 11 n. d.
14 24 h -- 82 68 52 15
15 10 h 88 (5 h) 18 10 11 n. d.
16 24 h -- 34 24 28 n. d.
29
Entry Phenol Time Yield () Yield () Yield () Yield () Yield ()
Entry Phenol Time BmimPF6 CH3NO2 THF CH3CN DMF
17 4 h 92 (2 h) 75 64 65 61
18 6 h -- 92 88 90 77
19 8 h -- -- -- -- 82
20 10 h 88 16 10 5 n. d.
21 24 h -- 38 23 14 n. d.
30
Entry Phenol Time Yield () Yield () Yield () Yield () Yield ()
Entry Phenol Time BmimPF6 CH3NO2 THF CH3CN DMF
22 24 h n. d. n. d. n. d. n. d. n. d.
23 24 h n. d. n. d. n. d. n. d. n. d.
24 24 h n. d. n. d. n. d. n. d. n. d.
31
Entry Phenol Yield () Yield () Entry Phenol Yield () Yield ()
Entry Phenol neat BmimPF6 Entry Phenol neat BmimPF6
1 98 (1 h) 91 (1 h) 69 (20 min) 8 82 (10 h) 88 (5 h)
2 80 (25 min) 84 (20 min) 9 84 (4 h) 92 (2 h)
3 75 (15 min) 82 (10 min) 10 81 (24h) 88 (10 h)
4 69 (15 min) 84 (15 min) 11 n. d. (24 h) n. d. (24 h)
5 69 (4 h) 82 (20 min) 12 n. d. (24 h) n. d. (24 h)
6 93 (10 h) 92 (6 h) 13 n. d. (24 h) n. d. (24 h)
7 91 (5 h) 93 (1 h) 71 (20 min)
32
Thermal Heating
Liquid boiling temperature is always lower than
surface temperature of container
Convection transition
33
Mechanism of Microwave Heating
Dipole Rotation
34
Ionic Conduction
35
Interactive Characteristic between Materials and
Microwave
Conductor (Metal Material)
Reflective
Insulator (Telflon)
Transparent
Dielectric Materials (Water)
Absorptive
36
Microwave Flash Heating
Microwave energy
Digestion bottle
Liquid raises temperature quickly
37
Preparation of Organomolybdenum Catalyst

• Microwave Flash Heating Conditions

38
Organomolybdenum Lewis Acid Catalyzed
Pechmann
Condensation

• Microwave Flash Heating Conditions

39
Entry Phenol Yield () Yield () Entry Phenol Yield () Yield ()
Entry Phenol neat BmimPF6 Entry Phenol neat BmimPF6
1 93 (7 min) 86 (7 min) 8 80 (15 min) 46 (17 min)
2 92 (5 min) 83 (3 min) 9 86 (10 min) 69 (10 min)
3 89 (3 min) 91 (1 min) 10 66 (17 min) 17 (17 min)
4 86 (6 min) 90 (2 min) 11 n. d. (17 min) n. d. (17 min)
5 73 (15 min) 84 (3 min) 12 n. d. (17 min) n. d. (17 min)
6 93 (17 min) 51 (17 min) 13 n. d. (17 min) n. d. (17 min)
7 91 (15 min) 68 (17 min)
40
Microwave Flash Heating and Power Supply Curve
41
Entry Phenol Thermal / Yield () Thermal / Yield () MW / Yield () MW / Yield ()
Entry Phenol neat BmimPF6 neat BmimPF6
1 98 (1 h) 91 (1 h) 69 (20 min) 93 (7 min) 86 (7 min) 94 (8 min)
2 80 (25 min) 84 (20 min) 92 (5 min) 83 (3 min)
3 75 (15 min) 82 (10 min) 89 (3 min) 91 (1 min)
4 69 (15 min) 84 (15 min) 86 (4 min) 90 (2 min)
5 69 (4 h) 82 (20 min) 73 (15 min) 84 (3 min)
42
Entry Phenol Thermal / Yield () Thermal / Yield () MW / Yield () MW / Yield ()
Entry Phenol neat BmimPF6 neat BmimPF6
6 93 (10 h) 92 (6 h) 93 (17 min) 51 (17 min)
7 91 (5 h) 93 (1 h) 71 (20 min) 91 (15 min) 68 (17 min)
8 82 (10 h) 88 (5 h) 80 (15 min) 46 (17 min)
9 84 (4 h) 92 (2 h) 86 (10 min) 69 (10 min)
10 81 (24 h) 88 (10 h) 66 (17 min) 17 (17 min)
43
Recyclability of Organomolybdenum Lewis Acid
Catalyst
Substrate
Adduct
Added
Extraction
CHCl3
Catalyst Solution
Ionic Liquid BmimPF6
44
Recyclability of Organomolybdenum Lewis Acid
Catalyst in bmimPF6
45
Proposed Mechanism
46
Proposed Mechanism
47
Catalytic Reactivity of A(2-py)3M(CO)(NO)22
on Pechmann Condensation
Catalysts Catalysts Yield ()
A(2-py)3 M Yield ()
OP(2-py)3 Mo 98
P(2-py)3 Mo 82
OP(2-py)3 W 74
P(2-py)3 W 71
48
Catalytic Reactivity of A(2-py)3M(CO)(NO)22 on
Mukaiyama Aldol Reaction
Catalysts Catalysts Yield ()
A(2-py)3 M Yield ()
OP(2-py)3 Mo 93
P(2-py)3 Mo 85
OP(2-py)3 W 56
P(2-py)3 W 45
??????? ???????????????Mukaiyama Aldol?????????
?????????, 2005.
49
Catalytic Reactivity of A(2-py)3M(CO)(NO)22 on
Diels Alder Reaction
Catalysts Catalysts Concentration (M) /Time (min) Yield () (endo exo)
A(2-py)3 M Concentration (M) /Time (min) Yield () (endo exo)
OP(2-py)3a W 0.67 / 45 97 (9010)
OP(2-py)3b Mo 0.67 / 45 85 (9010)
P(2-py)3c W 0.022 / 30 87 (946)
a??????? ???????????????????????Diels-Alde
??????????????, 2003. b???????
???????????????Mukaiyama Aldol?????????
?????????, 2005. c ??????? ?????????????????????
??? ?????????, 2001
50
Conclusions

• We have successfully demonstrated the catalytic
  activity of OP(2-py)3Mo(CO)(NO)2(BF4)2 for the
  synthesis of a variety of coumarins under
  solvent-free and ionic liquid system (BmimPF6)
  conditions. This practical and simple method led
  to good yields of the coumarin derivatives under
  mild conditions and within short times.
• The time economy, along with the conservation of
  the organomolybdenum Lewis acid catalyst activity
  and the high recovery of the Lewis acid catalyst,
  play for both low environmental impact and low
  cost. Other green advantages of the procedure are
  the low formation of wastes, easy purification
  and principally, the replacement of corrosive and
  environmental unfriendly acids.

51
Conclusions

• The successful use of microwave irradiation in
  providing this rapid and direct route to
  coumarins in comparison to classical procedures
  contributes to confirming the participation of
  specific effects in some microwave-assisted
  organic synthesis.
• Because the OP(2-py)3Mo(CO)(NO)2(BF4)2
  catalyst is relatively high moisture and oxygen
  stability, we use neutral ionic liquids,
  BmimPF6, for Pechmann condensation as a
  recyclable media, and still have good yield for
  several times.

52
Entry Phenol Thermal / Yield () Thermal / Yield () MW / Yield () MW / Yield ()
Entry Phenol neat BmimPF6 neat BmimPF6
11 n. d. (24 h) n. d. (24 h) n. d. (17 min) n. d. (17 min)
12 n. d. (24 h) n. d. (24 h) n. d. (17 min) n. d. (17 min)
13 n. d. (24 h) n. d. (24 h) n. d. (17 min) n. d. (17 min)