Tatiana Pachova BSc‐2, chemistry Assistant : Chandan Dey Sciences II – lab. A 7/12/11
The Reformatsky reaction (n°27)
1. INTRODUCTION
1.1) Purpose
The objective of this experiment is to synthesize the ethyl‐3‐hydroxy‐3‐ phenylpropanoate by a Reformatsky mechanism.
1.2) Scheme
OH
OEt CHO CO2Et Br 1. Zn + + O 2. H / H2O Ethyl-2-bromoacetate Chemical Formula: C H BrO Benzaldehyde 4 7 2 Ethyl-3-hydroxy-3-phenylpropanoate Chemical Formula: C7H6O Chemical Formula: C11H14O3 Molecular Weight: 194.23
1.3) Mechanism
OEt OEt OZnBr Br Zn(0) BrZn
O 1 O OEt
O
2 H
Zn2+Br
OH O O O
OEt H2O OEt 3
1. The zinc and the ethyl bromoacetate form a reformatsky enolate (an organozinc compound). This step is the oxidative addition 2. The enolate does a nucleophile substitution on the benzaldehyde and forms a chelate. 3. The addition of water allows forming the group hydroxyl and therefore the product.
The advantage of the Reformatsky reaction over an aldol condensation is that in the latter one, the product would have a double bond between the alpha and beta carbons. The aldol product undergoes elimination under acidic/basic conditions to afford an α, β unsaturated ester. O
OEt
Ethyl cinnamate
2. PROCEDURE
2.1) Preparation of the solvents
30mL of toluene are dried under a N2 atmosphere; on Na. Small pieces of the metal are slowly added in the flask containing the solvent. A balloon filled with N2 is fixed to the condenser. A spoon of benzophenone is added to the solution to show the change of color when the water and the O2 are no longer in the solvent. When it was dried, the solvent was distilled (under the N2 atmosphere) at about 112°C.
The same is done to 25mL of ether, distilled at about 37°C.
2.2) Reaction
Reagents molar mass [g/mol] wt/vol taken n [mmol] equivalence ethyl‐2‐bromoacetate 167.01 (d=1.506) 11.1mL 100 1 zinc (powder) 65.41 8g 120 1.2 benzaldehyde 106.12 (d=1.045) 12.4mL 120 1.2
All the equipment was dried before use. In a twin‐neck bottom flask of 250mL, dried zinc 8g was placed with a magnetic agitator. The addition funnel was filled with 11.1mL of ethyl‐2‐bromoacetate, 12.4mL of freshly distilled benzaldehyde, 16mL of toluene (distilled on Na under N2) and 5mL of ether (distilled on Na under N2). The solution was slowly (1h) poured into the flask, after the reaction began (after 2mL of solution + heating). Then, the solution was refluxed for 30min, cooled down with an ice/water bath and sulfuric acid 50mL 10% was added. In a separatory funnel the aqueous phase was separated and the organic phase was washed successively with H2SO4 10% (2x50mL), H2O (50mL), saturated NaHCO3 (2x30mL), H2O (2x20mL) and saturated NaCl (20mL). Then, the organic phase was dried on MgSO4, the solvent was separated on the rotary evaporator.
2.3) Isolation
After the solvent was evaporated, the product was distilled under vacuum (≈10mm) at about 160°C.
3. DISCUSSION & RESULTS
3.1) Observations
The reaction was very exothermic, but it wasn’t very easy to initiate: the reactive mixture needed to be warmed up with a hot fan for several minutes. Maybe with a preparation of zinc, it would have been easier (at the end, there was some zinc staying at the bottom of the flask). The refluxed solution was orange.
When distilling the reagents, the added benzophenone made the solution’s color to turn dark blue, when the water was “gone” and then it became violet when all the O2 was out of the solution (reacted with Na).
3.2) Yield
n th [mmol] n exp [mmol] yield [%] 100 52.14 52%
The limiting reagent is the ethyl‐2‐bromoacetate (100mmol). So nmax=100mmol. 10.1277g=52.14mmol of pure product were obtained at the end of the reaction, which gives a yield of 52%.
The loss of the product could be due to fact that the zinc wasn’t activated and that therefore the benzaldehyde may not have reacted completely. Otherwise, there were some problems with the vacuum, so maybe not the totality of the product was collected in the distillation at the end. 4. SPECTROMETRY DATA
1 4.1) NMR H (CDCl3, 400MHz) The multiplicity is given by 2nI+1 with I the spin number and n the number of neighboring equally coupled protons. For the 1H, I=1/2 and therefore the multiplicity is n+1.
H1 OH O
H6 H8
H2 O
H9
H7
H3 H5 H10
H11 H13 H4 H12
The specter obtained by MNR corresponds well to the values given by the protocol. It means that the product is clean.
δ 7.4‐7.27 (m, 5H) ; δ 5.15 (t, 1H) ; δ 4.18 (d, 2H, J=7.17Hz) ; δ 3.4 (s, 1H) ; δ 2.73 (q, 2H, J=8.84) ; δ 1.27 (t, 3H, J=7.09Hz)
bond shift ∂ th. [ppm] multiplicity hydrogen
C‐H 7.40‐7.34 doublet benzene H1, H5
C‐H 7.40‐7.34 doublet of doublets benzene H2, H4
C‐H 7.31‐7.27 triplet benzene H3
C‐H 5.15 triplet H6
C‐H 4.18 doublet H7, H8 O‐H 3.4 singlet alcool
C‐H 2.73 quartet H9, H10
C‐H 1.27 triplet methyl H11, H12, H13
In the benzene, there are 5 carbons: H1 and H5 are ortho, H2 and H4 are meta and H3 is para. So we expect 1 doublet, 1 doublet of doublets and 1 triplet, with different values. But, since the values are too close, we get a multiplet.
The hydrogen n°6 has 2 neighboring protons (H8 and H7), therefore the peak is a triplet. So, inversely H8 and H7 have one neighboring proton and therefore their peak is a doublet.
The H from the hydroxyl group is “by itself”, so its peak is a singlet.
The protons H9 and H10 have 3 neighboring protons from the methyl group and therefore the peak is a quartet. Inversely the hydrogens from the methyl group form a triplet peak.
4.2) IR (neat, cm‐1) 3443‐3490; 1958; 1730; 1504; 1466; 1379; 1274; 1183; 1163; 1041; 760; 702.
The specter obtained by IR shows that the substance, which is analyzed, is the product. In fact the specific groups correspond to the product, for example the OH: 3443‐3490.
Also there is a carbonyl group, which has theoretically a stretch at 1730cm‐1 and we find a long peak at 1728.
5. REFERENCES
[1] Travaux Pratiques de Chimie Organique 3ème Semestre, 21 Novembre 2011 – 16 Mars 2012, 27 [2] Silverstein, Bassler, Morrill, Spectrometric identification of organic compounds [3] Jie Jack Li, Name Reactions: A collection of Detailed Reaction Mechanisms, 2006, 487