指導教授 : 于淑君博士 2013 / 07 /25

1

Synthesis and Characterization of Aminodipyridylphosphine Oxide Iron(II)

Complexes. Catalytic Application on Microwave-Assisted Amidation of Aldehydes

指導教授 : 于淑君博士2013 / 07 /25

學生 : 蔡俊偉

2

Green Chemistry

化學反應的綠色化原子經濟反應產品的綠色化環境友好產品

溶劑的綠色化無毒無害的溶劑

原料的綠色化無毒無害的原料可再生資源

觸媒的綠色化無毒無害的觸媒

能源的綠色化提升能源的效率如微波

Chahbane, N.; Popescue, D., L.; Mitchell, D., A.; Chanda, A.; Lenoir, D.; Ryabov, A.D.; Schramm, K., W. and Collins, T., J. Green Chem. 2007, 9, 49–57.

3

Green Catalysts

• Solid acid catalysts– Ex, Nafion-H, SO4

2-/ZrO2 、 SO42-/TiO2, …

• HPA catalysts– H3PMo12O40, H4PW11VO40

• Zeolite catalysts– ZSM-5, X-type, Y-type

• Metal catalysts– heterogeneous catalysis, homogeneous catalysis

• EnzymeSheldon, R., A.; Arends, I., W.,C., E.; and Hanefeld, U. (2007) Green Chemistry and Catalysis, Wiley-VCH Verlag GmbH, Weinheim

4

Application of Green Chemistry

Sonogashira coupling

N

Cl+

Si(CH3)3

N

Si(CH3)3

time yield (%)Conventional 18 h 80

Microwave assisted 25 min 97

+ H2O2

NOHOH

OO

FeCl3. 6 H2O (5 mol%)

pyrrodlidine (10 mol%)

(10 mol%)

t-amyl alcohol/water (90/10)rt. 1 h

O

H2O

30% / 2 equiv

+

conv. 99%sel. 95%

+ H2O2

30% 3 equiv

0.5 mol %

Ru

NO

O

O

ON

N

N

t-AmOH / water (90/10)rt. 12 h

O

+ H2O

yield = 71 %

Epoxidation

物質動物 , 途徑

Lethal Dose, 50%

(LD50)

FeCl3.6H2O 大鼠 , 口服 1872 mg/ kg

FeCl2.4H2O 大鼠 , 口服 1678 mg/ kg

RuCl 3大鼠 , 口服 210 mg/kg

Anilkumar, G.; Bhor, S.; et. al. Tetrahedron Asymm., 2005 , 16, 3536–3561

Hasan, K.; Browne, N. and Kozak,C.,M. Green Chem., 2011, 13, 1230.

5

Phosphine Ligand Phosphines are electronically and sterically tunable.

Chemical waste - water bloom

Air/water sensitive and thermally unstable.

Metal leaching.

. Expensive.

P P PPO

OO

P(Bu)3 P(OiPr)3 P(Me)3 P(o-tolyl)3

R NH

PO

NN

R = CH3 = (CH3)8OH

Kinzel, E. J. Chem. Soc. Chem. Commun. 1986 1098.

6

The Importance of Fe(II)

• Iron is one of the most abundant metals on earth. (5.6% of earth’s crust. 4th most abundant element after oxygen, silicon, and aluminum.

• Iron is environmentally friendly metal

• Low toxic

• In body play a important role to transport oxygen (woman 2.5g ， man 4g) 60 mg/kg to iron poisoning

The Catalytic Applications of Fe(II)

Ring Opening Reactions

Kharasch Reaction

Cross-Coupling Reactions

Mukaiyama-aldol reaction

Cycloadditions[2+1]-Cycloadditions[2+2]-Cycloadditions

Acetalization

Diels-Alder Reaction

Sulfide Oxidations

Aminochlorination

Allylic Aminations

Baeyer-Villiger Reactions

Amidation Reaction

7

8

Amide Bond

R1 NR3

O

R2

Amide

R1P

NR3

O

R2

R

Phosphoramide

R1S

NR3

O

R2

O

Sulfonamide

C. A. G. N. Montalbetti, V. Falque Tetrahedron , 2005, 61, 10827–10852

+R H

OSO

ONI R N

OS

H

O

O

9

Application of Acyl Sulfonamides

HCV NS5B polymerase allosteric inhibitors

antitumor activity Navitoclax

S. Jana, F. Hof. J. Org. Chem. 2011, 76, 3733–3741

Hepatitis C Virus Non-structural protein 5B, NS5B

Acyl Sulfonamides

10

J. Chan,* K. D. Baucom, and J. A. Murry J. Am. Chem. Soc. 2007, , 129, 14106-14107

J. W. W. Chang and P. W. H. Chan*, et al. Angew. Chem. Int. Ed. 2008, 47, 1138-1140

J. W. W. Chang and P. W. H. Chan*,et.al. J. Org. Chem. 2011, 76, 4894-4904

SO O

R1 NH2+ H R2

O 2 mol% Rh2(esp)2

PHI(OC(O)tBu)0 to 50 oC, IPA, 24 h

SO O

R1 NH

R2

O

Me H

Me O+ PhI=NTs

5 mol% Ru(TTP)CO

CH2Cl2, RT, 1h Me NHTs

Me O

11

Motivation Well-defined structure Iron is environmentally friendly metal Iron is less expensive than other transition metals.

- Rh2(esp)2 $ 30172 USD/mol ReagentPlus® (Aldrich) - Ru(TTP)CO $ 20740 USD/mol reagent grade (Sigma-

Aldrich) - FeCl2

.4H2O $ 148 USD/mol reagent grade (Sigma-Aldrich) Using bipyridine ligand to replace phosphine ligand in

organomatallic catalysis. Microwave to replace thermal energy

HO NH

PO

NN

12

+Degas DMF

95 oC, 6 hourN3

[P(2-py)3]

NN

N

P1ml DI water

NH

PO

NN

Mix solvent MeOH:CH3CN= 1: 5, RT, 12 hour

Cat.

NH

PO

NN Fe

NH

PO

NN FeCl2.4H2O

HNP

O

NN

Cl

Cl

2

80 %

Br 1.NaN3 , DMF/H2O

2. 50 oC / 8 hour

N3

80 %

Synthesis of 4C-Ppy2 and (4C-Ppy2)2FeCl2

IR (KBr) : py CC NC,

Ring stretching = 1590(s), 1426(s) cm-1

80 %

IR Spectra of 4C-Ppy2 and (4C-Ppy2)2FeCl2

νC － C (Py ring)

νC － N (Py ring)

Wavenumber (cm-1)pyridine ring

vibration

ν(C = N) Δν

Ln- FeCl2a 1650 → 1668 18

PdCl2(2-pmOpe)2b 1594 → 1609 15

11C-Ppy2-Cu(OTf) 1570 → 1592 22

11C-Ppy2-NiBr2 1577 → 1592 15

11C-Ppy2-Pd(OAc)2 1574 → 1586 12

11C-Ppy2-MnCl2 1574 → 1586 12b.

b. a.

NH

PO

NN Fe

HNP

O

NN

Cl

Cl

Hahn, F. E.; Langehahn, V.; Lügger, T.; Pape, T.; Le Van, D. Angew. Chem. Int. Ed. 2005, 44, 3759-3763.

Zerong, L.; Zhongquan, L.; Ning, M. and Biao, W. Bull. Korean Chem. Soc. 2011, 32, 2537-3543

wavernumber

14

Iron Complexes –Catalyzed Amidation Reactions of Aldehyde with PhINTs

entry catalytic Yield(%)a

1 FeCl2 ． 4H2O 20 2 FeCl3 ． 6H2O 15 3 FeCl2 + 4C-Ppy2 90 4 FeCl3 + 4C-Ppy2 76

a Yields were determined by H-NMR. Reaction conditions: aldehyde (1 equiv.), PhINTs (1.5 equiv.), catalyst (0.05 equiv.), solvent = 0.67 mL, 50 oC, 3 hr

H

O

CHCl3, PhINTs, 40 oC, 3 h

O

NH

TsFe cat.5 mol %

15

AA Spectrum of [CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2

NH

PO

NN Fe

HNP

O

NN

Cl

Cl 1.46710-6 mol/mg Fe

2 4 6 8 10 12 14 160

0.1

0.2

0.3

0.4

0.5

0.6

f(x) = 0.0344666666666667 x + 0.0557999999999995R² = 0.996640441478057

Series1Linear (Series1)

ppm 吸收度3 0.153

6 0.267

9 0.365

12 0.483

15 0.562

mol/mg Fe

1 1.679 10-6

2 1.653 10-6

3 1.589 10-6

NH

PO

NN Fe

Cl

Cl2.48710-6 mol/mg Fe

Calculated base on chemical formula

experimental AA data

16

Colorimetry of [CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2

N N

1,10-Phenanthroline

Fe2+ + 3phen (phen)3Fe(II)

Visible spectrum of (phen)3Fe(II)

max = 510nm

(4C-Ppy2)2-FeCl2 (3)

mol/mg

FeCl2·4H2O

mol/mg

理論值 a 1.48 × 10-6 5.031 × 10-6

AA 實驗值 1.58 × 10-6 4.671 × 10-6

傳統比色分析 1.42× 10-6 3.783 × 10-6

二價鐵純度 b 80 % 81 %

a. Calculated base on chemical formula

b. ( 傳統比色分析 / AA 實驗值 ) × 100%Harvey, J.; Aubrey, E.; John, A. Smart, Analytical Chemistry 1955, 27, 26-29.

17

638.00 640.00 642.00 644.00 646.00 648.00 650.000.0

20.0

40.0

60.0

80.0

100.0

641.12

642.14

643.16

644.16639.16

641.14

643.16642.16

644.16

640.16

639.16

1020805_130705183651 #1236 RT: 2.52 AV:1 NL: 1.48E5T: ITMS + c ESI Full ms [150.00-2000.00]

350 400 450 500 550 600 650 700 750 800 850 900 950 1000m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

641.52

366.53

573.21435.35379.02 491.34 1000.32938.06550.28 613.35 722.47 889.44861.35752.26 824.49

ESI-MS Spectrum of [CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2

[CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2+

= 641 (m/z)

Simulated MS Data

Simulated MS Data

[CH3(CH2)3N(H)P(O)(2-py)2]FeCl2+

= 366 (m/z)

Experimental MS Data

NH

PO

NN H

NPO

NNFe

Cl



637 638 639 640 641 642 643 644 645 646 647m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

633.52

642.53

643.53

675.42

644.56

676.45 647.50

639.49645.61

646.55640.49

362.00 364.00 366.00 368.00 370.00 372.00 374.000.0

20.0

40.0

60.0

80.0

100.0

366.00

367.02

368.04

369.04364.04


359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

366.53

367.48

368.47

360.39

369.48

373.38 374.47361.42359.34 371.58

364.49

363.51 370.47362.49365.49

NH

PO

NN

FeCl

18

EPR Spectrum of [CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2

g = 2.199N

N N

NM

M = FeCl2

g = 2.04 (radical)

77 k, MeOH 300 k, MeOH

Li Zhong-Fang, et al. Chinese Journal of Inoranic chemistry 2003, 19.7, 691-698.

NH

PO

NN Fe

HNP

O

NN

Cl

Cl

19

+

Degas DMF

95 oC, 6 hourHO N3

[P(2-py)3]

NN

N

P 1ml DI water

Aminodipyridylphosphine Oxide Ligand

HO NH

PO

NN

80 %

HO Br1.NaN3 / DMF

2. RT / 6 hourHO N3

93 %

Synthesis of 11C-Ppy2

Lin, Y.-Y; Tsai, S.-C.; Yu, S. J. J. Org. Chem. 2008, 73, 4920-4928.

20

Synthesis of (11C-Ppy2)2-FeCl2

MeOH:CH3CN= 1: 5, RT, 12 hour

Cat.

HO NH

PO

NN Fe

HO NH

PO

NN FeCl2.4H2O

OHHNP

O

NN

Cl

Cl

IR (KBr) : py CC NC, Ring stretching = 1588(s), 1425 (s) cm-1

21

3000 2500 2000 1500 10000

20

40

60

80

100

120

140

160

180

B

A

L1 L1-FeCl2

IR Spectra of 11C-Ppy2 and (11C-Ppy2)2-FeCl2

1575cm-1

1424cm-1

1588cm-1

1426cm-1

Wavenumber

T( %

)

νC － C (Py ring)

νC － N (Py ring)

2

22

AA Spectrum of [HO(CH2)11N(H)P(O)(2-py)2]2FeCl2

HO NH

PO

NN Fe

Cl

Cl

HO NH

PO

NN Fe OH

HNP

O

NN

Cl

Cl

1.106 10-6 mol/mg Fe

1.937 10-6 mol/mg Fe

2 4 6 8 10 12 14 160

0.1

0.2

0.3

0.4

0.5

0.6f(x) = 0.0344666666666667 x + 0.0601999999999997R² = 0.993462133150962

mol/mg Fe

1 1.324 10-6

2 1.413 10-6

experimental AA data

Calculated base on chemical Formula

23

Colorimetry of [HO(CH2)11N(H)P(O)(2-py)2]2FeCl2

N N

1,10-Phenanthroline

Fe2+ + 3phen (phen)3Fe(II)

Visible spectrum of (phen)3Fe(II)

max = 510nm

(11C-Ppy2)2-FeCl2 (6)

mol/mg

FeCl2·4H2O

mol/mg

理論值 a 1.11 × 10-6 5.031 × 10-6

AA 實驗值 1.32 × 10-6 4.671 × 10-6

傳統比色分析 1.03× 10-6 3.783 × 10-6

二價鐵純度 b 78 % 81 %

a. Calculated base on chemical formula

b. ( 傳統比色分析 / AA 實驗值 ) × 100%Harvey, J.; Aubrey, E.; John, A. Smart, Analytical Chemistry 1955, 27, 26-29.

1020704_130705183651 #494-617 RT: 0.84-1.11 AV:93 NL: 6.98E6T: ITMS + c ESI Full ms [350.00-2000.00]

350 400 450 500 550 600 650 700 750 800 850 900 950 1000m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

390.36417.31

869.34

778.51 914.03444.27 965.38577.20480.28 833.38515.20372.41 630.10 664.33 700.38 942.37728.42547.56

ESI-MS Spectrum of [HO(CH2)11N(H)P(O)(2-py)2]2FeCl2

[HO3(CH2)11N(H)P(O)(2-py)2]2FeCl+ = 869 (m/z)

24

Simulated MS Data

HO NH

PO

NN Fe OH

HNP

O

NN

Cl


25

Optimization of Reaction Conditions

entry PhINTs(equiv.) temp. hour colvent conv.%1 2 rt 18 CH2Cl2 87%2 2 40 18 CH2Cl2 95%3 2 40 6 CH2Cl2 85%4 0.5 40 6 CH2Cl2 56%5 1.5 40 6 CH2Cl2 88%6 1.5 40 3 CH2Cl2 56%7 1.5 40 3 CHCl3 89%8 1.5 40 3 CH3CN 65%9b 1.5 40 18 CHCl3 30%10 1.5 rt 3 CHCl3 50%

[CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2

+5 mol %H

O

SO

ONI N

OS

H

O

O

5 mol %

b. no cat.

26

entry solvent time (hr)

Polarity (P ＊ ) yielda (%)

1 CHCl3 3 4.1 892 CH2Cl2 3 3.1 563 CH2Cl2 6 854 CH3CN 3 5.8 655 CH2Cl2 : Toluene = 1 : 1 3 0.5 × 3.1 + 0.5 × 2.4 246 CHCl3 : Toluene = 2 : 1 3 0.67 × 4.1 + 0.33 × 2.4 187 MeOH 3 5.1 208 DMSO 3 7.2 NA9 [Bmim]Br 3 13

a Yields were determined by H-NMR. Reaction conditions: aldehyde (1 equiv.), PhINTs (1.5 equiv.), catalyst (0.05 equiv.), solvent = 0.67 mL, 40 oC, 3 hr NA = not available

Reaction Conditions ScreeningCH3(CH2)3N(H)P(O)(2-py)2]2FeCl2

+5 mol %H

O

SO

ONI N

OS

H

O

O

P ＊AB=QAP ＊

A+QBP ＊B [Bmim]PF6 dipole moment 14.89 D

27

CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2

+5 mol %

CHCl3, 40oC, 3hR H

OSO

ONI R N

OS

H

O

O

(4C-Ppy2)2-Fe(II) Complex –Catalyzed Amidation Reactions of Aldehyde with PhINTs

General reaction conditions: Aldehyde (1 equiv.), PhINTs (1.5 equiv.), Catalyst (0.05 equiv.) Solvent = 0.67 mL, 40 oC, 3 h. a Yields were determined by 1H-NMR. b. PhINTs = 2 equiv. c 18 h

Summary of Fe(II) catalytic ActivityEntry Product (4C-Ppy2)2-

FeCl2

Yield(%)a

(11C-Ppy2)2-FeCl2

Yield(%)a

Entry Product (4C-Ppy2)2-FeCl2

Yield(%)a

(11C-Ppy2)2-FeCl2

Yield(%)a

1 90 86 7 90 85

2 92 87 8 85 77

3 82 80 9 85 86

4 90 85 10 78 75

5 5964b

57 11 6784b

65

6 92 83 12 87 80

NH

O

Ts NH

O

Ts

NH

O

TsNH

O

F

Ts

NH

O

nn = 6

Ts NH

O

Br

Ts

NH

O

TsNH

O

Ts

NH

O

Ts NH

O

MeO

Ts

NH

O

Ts NH

O

Ts

General reaction conditions: Aldehyde (1 equiv.), PhINTs (1.5 equiv.), Catalyst (0.05 equiv.) Solvent = 0.67 mL, 40 oC, 3 h. a Yields were determined by 1H-NMR. b. PhINTs = 2.0 equiv.

29

Proposed Mechanism of Amidation Reactions of Aldehyde with PhINTs

RNH

PO

NN

Fe N SO

O

4+

SN

IO O Ph

RNH

PO

NN

FeCl

Cl

2

NN Fe N Ts

R

OH

R H

O

Product

R NH

OTs

RNH

PO

NN

Fe

I

SN

IO O Ph

I

2+

H2O

SNH2

O O

2

2

J. W. W. Chang and P. W. H. Chan* J. Org. Chem. 2011, 76, 4894-4904

byproduct

30

Microwave Assisted Amidation Reactions of Aldehyde with PhINTs

entry M.W. power

time. ( s ) solvent Yield Dielectric loss

1 300W 5min CHCl3 29% 0.432 300W 5min CHCl3 + 3drop [Bmim]

[PF6]20%

3 300W 2min DMSO No product 37.124b 300W 5min CHCl3 5%5 300W 5min CHCl3 + 1 drop DMSO 11% 0.43+37.126 600w 7min CHCl3 53%,7 600w 7min CHCl3 + 1 drop MeOH 28% 0.43+21.48 600w 7min CHCl3 + 1 drop DI

water22%, 0.43+9.89

9c 600w 7min CHCl3 67%10d 600w 7min CHCl3 87%

a Yields were determined by H-NMR. Reaction conditions: aldehyde (1 equiv.), PhINTs (1.5 equiv.), catalyst (0.05 equiv.), solvent = 0.67 mL. b no cat. . c aldehyde = 0.4 mol PhINTs = 0.6 mol Fe cat. = 10 mol% solvent = 1 ml. d solvent = 0.4 mL

H

O

M.W.PhINTs

O

NH

Ts4C-Fe cat.

[Bmim][PF6] dipole moment 14.82 D

31

Optimization of Reaction Conditions under Focused Microwave

entry M.W. power

time. ( min )

aldehyde ( M) temp. (oC)

yield(%)

1 50 W 1 0.5 35 30%2 100w 1 0.5 43 40%3 150W 1 0.5 64 47%4 150W 2 0.5 63 52%5 150W 5 0.5 66 68%

150W 8 0.5 65 77%6 150W 10 0.5 70 75%7 150W 1 0.5M+1 drop BmimBr 69 76%8 150W 3 0.5M+1 drop BmimBr 83 88%9 150W 3 0.5M+2 drop BmimBr 124 67%

10 150W 5 0.5M+1 drop BmimBr 95 91%11 200W 1 0.5 66 57%

12 200W 1 0.5 M+1 drop BmimBr 110 54% 13 250W 1 0.5 62 63%

14 250W 2 0.5 68 51%a Yields were determined by H-NMR. Reaction conditions: aldehyde = 0.2 mol (1 equiv.), PhINTs (1.5 equiv.), catalyst (0.05 equiv.), solvent CHCl3 = 0.4 mL .

H

O

Focus M.W.

O

NH

Ts4C-Fe cat.+ S

O

ONI

32

(4C-Ppy2)2-Fe(II) Complex Catalyzed Amidation Reactions of Aldehyde with PhINTs

a Yields were determined by H-NMR. Reaction conditions: aldehyde = 0.2 mol (1 equiv.), PhINTs (1.5 equiv.), catalyst (0.05 equiv.), solvent CHCl3 = 0.4 mL. b PhINTs (2.0 equiv)

33

Summary of Fe(II) Catalytic Activity under Focused Microwave



Yield(%)a

(11C-Ppy2)2-FeCl2

Yield(%)a


Yield(%)a

(11C-Ppy2)2-FeCl2

Yield(%)a

1 90 80 7 82 73

2 93 83 8 86 72

3 76 64 9 71 63

4 86 78 10 75 75

5 54 50 11 80b 65b

6 90 80 12 84 68

NH

O

TsNH

O

Ts

NH

O

Ts NH

O

F

Ts

NH

O

nn = 6

Ts NH

O

Br

Ts

NH

O

Ts NH

O

Ts

NH

O

Ts NH

O

MeO

Ts

NH

O

Ts NH

O

Ts

SSS S S

SSS

HS(CH2)11NH

P(2-py)2

O

HAuCl4. 4H2O

2. CH3(CH2)7SH/CHCl33. NaBH4/H2O/12h

1. [CH3(CH2)7]4N+Br-/CHCl3/rt/1h

CHCl3, 65oC,16 h

N P(2-py)2

OH

S

S S S

S

N P(2-py)2O

H

NH

O(2-py)2P

SS S

N

S

S S S

SNPH

SS S

Au

Au Au

NH

O(2-py)2P

O

NPH

OCl2Fe(2-py)2

HPO

NH

PO

(2-py)2FeCl2

FeCl2.4H2O/ dry CHCl3:MeOH = 6 :1

rt / 16 hr

(2-py)2FeCl2

Cl2Fe(2-py)2

34

Synthesis of the RS-Au-L1-FeCl2

RS-Au-L1-FeCl2RS-Au-L1

Au-RSRS = CH3(CH2)7SH

35

3500 3000 2500 2000 1500 1000-20

0

20

40

60

80

100

120

140

160

B

A

Au-L1-FeCl2 Au-L1 L1

IR Spectra of L1 ,Au-L1 and Au-L1-FeCl2

1575cm-1

1585cm-1

1426cm-1

1428cm-1

1575cm-1

1422cm-1

Wavenumber

T (%

)

36

9

N P(2-py)2

OH

S

S S S

S

N P(2-py)2

O

HNH

O(2-py)2P

SS SAu

NH

O(2-py)2P

TEM Image of RS-Au-L1-FeCl2

Particle size distribution 7.32 ± 1.2 nm

N

S

S S S

SNPH

SS SAu

O

NPH

OCl2Fe(2-py)2

HPO

NH

PO

(2-py)2FeCl2

(2-py)2FeCl2

Cl2Fe(2-py)2


FeRS-Au-L1

Element Weight%

Atomic%

Fe 6.23 7.05Cu 70.60 70.21Au 19.67 6.31

37

H

O

CHCl3, PhINTs, 40 oC, 3 h

O

NH

TsRS-Au-L1-FeCl2

5 mol %

RS-Au-L1-FeCl2 Complex –Catalyzed Amidation Reactions of Aldehyde with PhINTs

30 %


38

Summary

1.We have successfully synthesized green catalysts [4C-Ppy2]2-FeCl2 、 [ 11C-Ppy2]2-FeCl2 .Their structures were studied by IR, ESI-MS, AA, EPR spectroscopies

2.We have successfully demonstrated the catalytic activity of the Fe(II) complexes for amidation reactions of aldehyde with PhINTs.

3. The Fe(II)-catalyzed amidation reactions of aldehyde with PhINTs can be further accelerated under microwave irradiation conditions.

40

4C-Ppy2-FeCl2 (3) 11C-Ppy2-FeCl2 (6) FeCl2.6H2O

AA 理論值 1.48 × 10-6 mol/mg 1.11 × 10-6 mol/mg 5.031 × 10-6 mol/mg

AA 實驗值 1.58 × 10-6 mol/mg 1.32 × 10-6 mol/mg 4.671 × 10-6 mol/mg

傳統比色分析 1.42× 10-6 mol/mg 1.03× 10-6 mol/mg 3.783 × 10-6 mol/mg

二價鐵純度 a 80 % 78 % 81 %

a. ( 傳統比色分析 / AA 實驗值 ) × 100%

41

瓦數時間焦耳600 W 7 min 252000 5.5 倍150 W 5 min 45000 31 倍130 W 180*60 1404000 傳統加熱

620 W 300 oC 6 格呈線性1.3 格 130W 40 oC

42

(11C-Ppy2)2-Fe(II) Complex Catalyzed Amidation Reactions of Aldehyde with PhINTs


44

表 3.12 用 [CH3(CH2)3N(H)P(O)(2-py)2]2FeCl2 (3) 鐵催化劑對於PhINTs 競爭反應進行 amidation 反應的催化結果

entry solvent yield (%)a byproductyield (%)a

1 thermal CHCl3 90 322 thermal CHCl3 + 1.1 mol DI water 26 823 microwave CHCl3 90 334 microwave CHCl3 + 1.1 mol DI water 10 765b thermal CHCl3 + 1.1 mol DI water NA 456c thermal CHCl3+ 1.1 mol DI water NA 80

H

O O

NH

Ts

SO

ONI

[CH3(CH2)3P(O)(2-py)2]2FeCl25 mol %

SO

OH2N+

a Yields were determined by H-NMR. Reaction conditions: aldehyde = 0.2 mol (1 equiv.), PhINTs (1.5 equiv.), catalyst (0.05 equiv.), solvent CHCl3 = 0.67 mL (thermal) 0.4 mL (MW).b no Fe cat. C no aldehyde

1

45

Reproposed Mechanism of Amidation Reactions of Aldehyde with PhINTs

J. W. W. Chang and P. W. H. Chan* J. Org. Chem. 2011, 76, 4894-4904

46

non classed Staudinger reaction mechanism

R N N N + Ppy

yp

ypR N N N

P pyyp

py

N

N N

P pypy

pyR

N N NP pypypy

R

N P pypypy

R

H2OOH

H+ N Ppypy

ROH

N

H O

Ppy

pyR N

H O

Ppy

pyR

py H+

47

Staudinger reaction mechanism

48

P P PPOO

O

P(Bu)3 P(OiPr)3 P(Me)3 P(o-tolyl)3

25 mL 211.5 USD

25 G 396 USD

100 mL 31.9 USD

10G 135.5USD

49

理論值 =0.0002 mol*0.05 = 0.00001mol

0.00001*55.845/15.584 × 10-4g (in 1ml )

CHCl3 (ml)Aldehyde (mol)

Temp./Time AA (mg/L)取 0.1 ml total Fe g

4C-0.2M 1 0.2 40oC/3h 4.614 4.614 × 10-4g

4C-0.3M 1 0.3 40oC/3h 6.786 6.786 × 10-4g

4C-0.2M 1 0.2 Rt. / 10 min 4.005 4.005 × 10-4g

4C-0.3M 1 0.3 Rt. / 10 min 3.779 3.779 × 10-4g

11C-0.2M 1 0.2 40oC/3h 3.560 3.560 × 10-4g

11C-0.3M 1 0.3 40oC/3h 3.615 3.615 × 10-4g

50

NaN3 / DMF

rt / 6hrBr OH N3 OH

PBr3 / ether

rt / 6hr

N3 Br

97 %

50 %

1. CS(NH2)2 / ethanol

2. reflux , 16 hr

3. NaOH / 5 min

4. HCl /20 min

HS N3

90 %

P(2-py)3

H2O / CH3CN

110 oC / 16 h

NHSH

PO

NN

47%

Synthesis of Spacer-Linker

Lin, Y.-Y; Tsai, S.-C.; Yu, S. J. J. Org. Chem. 2008, 73, 4920-4928.

L1

1H NMR Spectra of Au NPs L1 and L1-Metal

51

RS-Au-L1-FeCl2

RS-Au-L1

d4-MeOH ＊

9

N P(2-py)2

OH

S

S S S

S

N P(2-py)2

O

HNH

O(2-py)2P

SS SAu

NH

O(2-py)2P

Py

N-H

NHSH

PO

NN

N-H

52

物質動物 , 途徑 Lethal Dose, 50%

(LD50)

水大鼠 , 口服 >90,000mg/kg

甲醇大鼠 , 口服 5,628 mg/kg

氯化鈉大鼠 , 口服 3,000 mg/kg

維他命A 大鼠 , 口服 2,000 mg/kg

二氯化亞鐵大鼠 , 口服 1678mg /kg

三氯化鐵大鼠 , 口服 1872mg/ kg

釕鹽

http://zh.wikipedia.org/wiki/%E6%B0%B4

http://zh.wikipedia.org/wiki/%E7%94%B2%E9%86%87

http://zh.wikipedia.org/wiki/%E6%B0%AF%E5%8C%96%E9%88%89

http://zh.wikipedia.org/wiki/%E7%B6%AD%E4%BB%96%E5%91%BDA

http://zh.wikipedia.org/wiki/%E7%B6%AD%E4%BB%96%E5%91%BDA

53

[CH3(CH2)11N(H)P(O)(2-py)2]2FeCl2

+5 mol %

CHCl3, 40oC, 3hR H

OSO

ONI R N

OS

H

O

O

(11C-Ppy2)2 -FeCl2 Complex –Catalyzed Amidation Reactions of Aldehyde with PhINTs

General reaction conditions: Aldehyde (1 equiv.), PhINTs (1.5 equiv.), Catalyst (0.05 equiv.) Solvent = 0.67 mL, 40 oC, 3 h. a Yields were determined by 1H-NMR. b. PhINTs = 2.0 equiv.

指導教授 : 于淑君 博士 2013 / 07 /25

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指導教授 : 于淑君博士 2013 / 07 /25