1. Ibrahim Sultan Mashima Laboratory Osaka University 2019/07/24
4,4’-Bipyridyl-catalyzed Reduction of Nitroarenes by Bis(neopentylglycolato)diboron
Ibrahim Sultan
Mashima Laboratory
Osaka University
2019/07/24

2. Contents…. Introduction Previous Work Background Reaction Optimization
Catalyst Screening
Substrate Synthesis
Substrate Scope
Mechanistic Study
Imine Synthesis
Future Work

3. Introduction 4 Million Ton Aniline production/year
Global Synthetic and Bio-based Aniline Market in 2017, by Application
Market Research Future ( market-5981)
Methyl di-phenylene isocyanate (MDI)-primarily used in rigid polyurethane (PU) foams.

4. Previous Work Beller et. Al., Chem. Rev. 2019, 119, 2611
Chemoselectivity,
Special high pressure equipment,
Inflammable hydrogen gas,
Hazardous reagents,
Relatively expensive metal complexes.
Beller et. Al., Chem. Rev. 2019, 119, 2611
Corma et. Al., Science 2006,313, 332.

5. Catalyst
“catalysis” term was first introduced by
Jons Jacob Berzelius in 1835
“A catalyst is a substance which affects the rate of a chemical reaction without being part of its end products”
“catalyst” was firstly Defined by Wilhelm Ostwald in 1900 5
Ertl, G. Reactions at surfaces: from atoms to complexity (Nobel Lecture).
 Angew. Chem. Int. Ed.  , 3524–3535

6. Background Mashima et. al., Chem. Eur. J. 2018, 24, 11278.
Suginome et al., Am. Chem. Soc. 2015, 137, 2852

7. Reaction Optimization
(a) The reactions carried out in the J-young NMR tubes. (b)The yield was calculated by GC analysis using the dodecane as an internal reagent. (c)7.2 μL of H2O was added. (d)Degasification by Sonification was carried out for 3 minutes upon mixing all reagents and 1 h later after putting in oil bath, mixture was gently shaken.
Entry 1a
(mmole)
B2Nep2 (equiv.)
Bipyridyl (mol %)
CH3CN
(mL)
Time
(hr) 2a
( %)(b)
Conv
(%)(b) 1
0.1
3.3
2,2'-bipy 5 mol%
0.5 24 14 20 2
4,4'-bipy 5 mol% 78 81 3
3.6 86
>99 4
0.4
1.5 18 94 97 5 6 84
6(c)
0.75 82 75 7
4,4'-bipy 0.5 mol% 63 8
4,4'-bipy 0.25mol% 64
9(d)
4,4'-bipy 2 mol% 93 99

8. Reductant-Boron Screening
Entry
reductant
Conv. (%)b 2a
(%)b 1
B2nep2
>99 93 7d 89 2c 91 85 8e 49 39 3
B2hex2 9f 4
n.d.
B2pin2 2 10
HBpin 8 6 5
B2cat2 83 11
H3B·NMe3
B2(OH)4 99 86 12
Me2PhSiBpin
a Conditions: nitrobenzene (0.40 mmol), boron compound (1.44 mmol), 4,4-bipyridine (2 mol%, relative to nitrobenzene), CH3CN (1.5 mL), 100 °C, 6 h, under air in J-young NMR tube. b Determined by GC using dodecane as internal standard. c Reaction under Ar. d 1 mol% of 4,4’-bipyridyl. e Reaction at room temperature for 24 h. f No 4,4bipyridyl’-.

9. Catalyst Screening Entry Catalyst 2a ( %)(b) Conv (%) 1 2,2'-bipirdyl
(a)Conditions: In J-young tube nitrobenzene (0.4mmol), B2Nep2(1.4mmol), catalyst loading relative to the 1a (2mol%), CH3CN (1.5mL), 1000C, 6hr. Under air. (b) Determined by GC analysis and using the dodecane as an internal standard.
Entry
Catalyst
2a ( %)(b)
Conv (%) 1
2,2'-bipirdyl 2 9
3,3-bipyridyl 3 6
1,10-phenanthroline 42 52 4
Pyrazine 8 14 5
2,3-dimethylpyrazine
2,5-dimethylpyrazine 15 21 7
2,6-dimethylpyrazine 43 59
2,3,5,6-tetramethylpyrazine

10. Catalyst Screening Li at el.Angew.Chem. Int .Ed. 2016 , 55 ,5 985
Entry
Catalyst
2a ( %)(b)
Conv (%) 9
Quinoxaline 11 21 10
Phenazine 2 5
Pyridine 13 12
2,6-dimethypyridine
4-phenylpyridine 4 18 14
4-Cyanopyradine 17 24 15
Quinoline 16
Isoquinoline
Li at el.Angew.Chem. Int .Ed , 55 ,5 985

11. Substrate Synthesis Org. Lett. 2008, 10 (19), 4383-4386
Org. Lett. 2012, 14 (7), 
J. Heterocyclic Chem. 2018, 55, 1917

12. Substrate Scope 12

13. Substrate Scope

14. Substrate Scope

15. Substrate Scope 15

16. Substrate Scope 16 16

17. Mechanistic Study 17 17 17 17

18. Mechanistic Study 18 18 18 18 18

19. Mechanistic Study 19 19 19 19 19 19

20. Proposed Mechanism 20 20 20

21. Application-Ketimine Synthesis
1 2 equiv of acetophenone was used 21 21 21 21

22. Imine Synthesis

23. Continue…
In the absence of carbonyl compound the main product observed by 1H NMR is:
Future Work
Scope for aldimine formation from the reduction of azoarenes in the presence of aldehyde.

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