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4th January 2017 @ 12:34

Buchwald-Hartwig Coupling reaction between 2-Phenyl-1,3-dioxolane and Piperidine to form 1-(3-(1,3-dioxolan-2-yl)phenyl)piperidine.


This reaction was executed on the 7/11/16 and finished on 14/11/16. This reaction's method is nearly identical to our first attempt at the Buchwald-Hartwig coupling reaction, the mere difference is the change in reagent from 3-bromobenzaldehyde.


 

Reaction Scheme:


scheme for protected with piperidine



Moles and weighings:

Compound

Weight (g)

Mw

Moles (mmol

2-Phenyl-1,3-dioxolane

0.0957

150.17

0.64

Toluene

4.2mL

92.14

 

Na-t-Bu

0.0517

96.10

0.54

BINAP

0.0027

622.67

4.34x10-4

Pd(dba)2

1.9x10­-3

575.00

0.003

Piperidine

4.87

85.15

57.2

 

 

Method:


This method was inspired by the Sigma Aldrich Cross Coupling reaction manual. All moles, weights and equivalents were based on the manual.

2-Phenyl-1,3-dioxolane (0.09570g), Piperidine (4.2mL), BINAP (0.00217g), Na-t-Bu (0.0517g) and Toluene (4.2 mL) were mixed altogether and degassed for 20 minutes. An N2 atmosphere was introduced while Pd(dba)2 (1.9mg) was added to the mixture. The reaction was left for 24 h under N2 and 70oC.

TLC analysis was performed on the crude product using 90:10 ratio of EtOac/Pet.ether…..

tlc protected group png.png

 

The Reaction was left for a further week.

TLC was done again with the same ratio, the crude product was then purified via rot.vap which gave 0.1403g of product. When compared to the theoretical mass of product (0.1474g), a yield of 95.2% was calculated. 

protected coupling tlc 2 png.png

 

NMR's were taken of the sample however no sign of the desired product was found. 

 

protected nmr 1 png.png

protected nmr 2 png.png

 

References:

  1. Betti, Matteo; Genesio, Eva; Marconi, Guido; Sanna Coccone, Salvatore; Wiedenau, Paul
    Organic Process Research and Development, 2014 ,  vol. 18,  # 6  p. 699 – 708
  2. Cross-Coupling Reaction Manual: Desk Reference, Dr Nick Bruno, Add Adlrich, http://www.sigmaaldrich.com/chemistry/chemical-synthesis/learning-center/cross-coupling-guide.html, accessed on 10/11/16

 

Attached Files
3rd January 2017 @ 13:28

Buchwald Hartwig coupling between 2-(3-Bromophenyl)-1,3-dioxolane and Piperidine using Pd(OAc)2 as a catalyst.

This expeiriment was performed on 14/11/16 - 15/11/16 

the Sigma Aldrich cross coupling guide was used to determine a method for this experiment, all theoretical values including moles, weights and equivelants were used as a template from this guide and applied to our own experiments.

 

Reaction Scheme:

 

 reaction scheme           

 

 

Moles and Weighings:

Compound

Mw

Weight (mg)

   Moles (mmol)

2-(3-bromophenyl)-1,3-dioxolane

229.07

300

1.31

Toluene

92.14

15mL

 

Piperidine

85.15

135

1.59

Pd(OAc)

224.51

5.84

0.026

BINAP

622.67

21

0.034

Na-t-Bu

96.10

190

1.98

 

 

Method:

2-(3-bromophenyl)-1,3-dioxolane (300mg), toluene (15ml), piperidine (135mg), BINAP (21mg) and Na-t-Bu (190mg) were all added and mixed together. This mixture was then degassed for 15 minutes before Pd(OAc)2 (5.84 mg) was added under inert (N) conditions. The reaction was left under 70oC for 16 h.TLC analysis was performed using a mobile phase of 90:10 EtOAc/Pet.Ether.

acetate catalyst TLC png.png

 

NMR analysis was performed where it showed no desired product being present. This may be due to the air sensitivity of the catalyst as the colour of the curde product has a correlation to the catalyst being made redundant during the experiment.

 

Nmr acetate experiment.png

References:

  1. Cross-Coupling Reaction Manual: Desk Reference, Dr Nick Bruno, Add Adlrich, http://www.sigmaaldrich.com/chemistry/chemical-synthesis/learning-center/cross-coupling-guide.html, accessed on 08/11/2016
  2. Betti, Matteo; Genesio, Eva; Marconi, Guido; Sanna Coccone, Salvatore; Wiedenau, Paul

            Organic Process Research and Development, 2014 ,  vol. 18,  # 6  p. 699 - 708

Attached Files
3rd January 2017 @ 12:35

3-Bromobenzaldehyde to 3-Piperidinylbenzaldehyde using the Buchwald-Hartwig coupling reaction.

 

Reaction scheme:

 

 

 

 

 

 

 

 

Chemical

Quantity (g/ml)

Mw

mmol

3-Bromobenzaldehyde

0.8ml

185.00

 6.86

3-Piperidinylbenzaldehyde

N/A

189.00

BINAP

0.0268g

622.67

0.04

PhMe

3ml

92.14

28.22 

Pd(dba)2

0.026g

575.00

0.05

Na-t-Bu

0.156g

96.10

1.62

Piperidine

0.076g

85.15

0.89 

 

 

Method:

3-Bromobenzaldehyde (0.8ml) was added to a round bottom flask along with Toluene (3ml), Piperidine (0.1ml), Na-t-Bu (0.15g) and BINAP (0.021g), this mixture was degassed for 20 minutes. Pd(dba)2 (0.026g) was added to the reaction mixture and was put under Inert (Nitrogen) conditions.

 

IMG_1431.png

 

 

The reaction monitored by TLC (70% EtOAc/Pet.Ether), the reaction was left overnight under heat and under a Nitrogen atmosphere.

 

 
 
IMG_1482.png

Rotary evaporation was performed to give an oily liquid left in the round bottomed flask however when an 1H NMR spectrum of the reaction mixture was analysed, there was no desired product present in the spectrum. The method was then altered and changed from here for the next experiment.

From here we decided to use a protecting group on our next experiment along with using Benzaldehyde 

 This reaction was executed on the 10/10/16 and finished on the 11/10/16

References: 

1. C. Fattorusso, G. Campiani, G. Kukreja, M. Persico, S. Butini, M. Romano, M. Altarelli, S. Ros, M. Brindisi, L. Savini, E. Novellino, V. Nacci, E. Fattorusso, S. Parapini, N. Basilico, D. Taramelli, V. Yardley, S. Croft, M. Borriello and S. Gemma, J. Med. Chem., 2008, 51, 1333-1343.

Attached Files
26th October 2016 @ 13:32

Protecting Benzaldehyde to give 2-Phenyl-1,3 dioxolane

 

Reaction Scheme

 

 

 Dioxane pt 1

    

 

 

Weighings, Moles and Molecular weights:

 

Chemical

Quantity (g/ml)

Mw

mmol

Benzaldehyde

8ml

106.12

78.7

Ethylene Glycol

6ml

62.07

107.6

Toluene-4-sulphonic acid monohydrate (Tosylic acid)

0.186g

172.20

1.08

PhMe

40ml

92.14

375.5

Saturated Sodium Bicarbonate

35g

84.07

416.6

Ethyl acetate

(analysis)

88.11

 -

2-phenyl-1,3 dioxane (product)

 -

150.17

 - 

 

 

Method:

Benzaldehyde (8mL, 78.7mmol), ethylene glycol (6mL, 107.6 mmol), tosic acid (0.186g, 1.08 mmol) and toluene (80mL) were at reflux overnight.

 

The reaction was monitored by TLC (90% EtOAc/Pet.Ether). After 12 hours the reaction was quenched with sat. aq. NaHCO3 and the ogranic phase separated. The solvent was removed in vacuo and crude 1H NMR obtained (CDCl3). The NMR data showed the reaction contained a mixture of starting material and desired product.

 

IMG_1483.png
IMG_1464.JPG

Separation was attempted by flash column chromatography (2-10% EtOAc/Pet.Ether) and product was isolated however 1H NMR showed that the material was not clean. 

IMG_1453 (1).png
IMG_1444.png

 

 

  1. 1.     Kamitori, Yasuhiro; Hojo, Masaru; Masuda, Ryoichi; Yoshida, Tatsushi, Tetrahedron Letters, 1985 ,  vol. 26,  # 39  p. 4767 – 4770
Attached Files