Synthesis Proposal

Multistep synthesis of 2, 6-bis (benzylidene) cyclohexanone
Chemistry 145
Omorade Payne
24th
March 2015
1. Background
Many studies conducted on α, α’-bis (substituted-benzylidene) cycloalkanones, have
shown there importance as precursors in numerous areas as well as their ability to serve as
intermediates for the synthesis of other organic compounds.
Firstly, some biological activities that α, α’-bis (substituted-benzylidene) cycloalkanones
are used for include: as antiangiogenics (anti-cancer therapies), as quinine reductase inducers
(cancer chemoprevention), as bis-spiropyrrolidines (enzyme inhibitors) and as arginine
methyltransferase inhibitors (protein modifiers). 1 Furthermore, these compounds are cytotoxic
(can control cell death) and have cholesterol-lowering properties. 2
Secondly, these compounds are also used as agrochemical, pharmaceutical and perfume
intermediates and in polymer synthesis. 3 In addition, they are known to possess drug resistance
reversal properties. 4
Thirdly, these carbonyl compounds are useful synthetic tools in natural products
chemistry. For example, α, α’-bis (benzylidene) cyclohexanone is an intermediate for the
synthesis of pyrimidine derivatives. 5 Moreover, they also serve as the intermediates for the
synthesis of 2, 7-disubstituted tropones which in turn are the synthetic intermediates for natural
products such as the cystodytins. 6

2. Synthetic Strategy
The general synthesis procedure for preparing α, α’-bis (substituted-benzylidene)
cycloalkanones is via the Aldol reaction. The two necessary precursors for this procedure are a
substituted benzaldehyde and cycloalkanones. 7 Thus, in order to prepare the product 2, 6-bis
(benzylidene) cyclohexanone, we first have to synthesize benzaldehyde and cyclohexanone.
a. Cyclohexene to Cyclohexanone 8, 9, 10
b. Benzene to Benzaldehyde 11, 12 13, 14, 15, 16, 17, 18, 19, 20, 21

Secondly, after having synthesize these two precursors, we can carry out the base
catalyzed Aldol condensation reaction (with loss of water) of benzaldehyde with cyclohexanone
to obtain the product 2, 6-bis (benzylidene) cyclohexanone.
c. Aldol ReactionSynthesis of 2, 6-bis (benzylidene) cyclohexanone
22, 23, 24, 25, 26
3. Experimental Section
a. Cyclohexene to Cyclohexanone
i. Cyclohexanolfrom Cyclohexene 27, 28
Scale: 0.12 mole (12.3 mL; 10g) of cyclohexene.
Procedure:
Collect 9 mL of concentrated sulfuric acid and 4 mL of distilled water in separate
graduated cylinders and cool in an ice bath. Slowly and carefully, add the cool acid and distilled
water to a stoppered 125 mL Erlenmeyer flask. Allow the solution to cool to room temperature.

Add 12.3 mL of cyclohexene, stopper the flask and shake. If heat evolves, cool the reaction
mixture in an ice bath. Keep shaking until a clear, homogenous solution is formed.
Pour the reaction mixture into a 250 mL round-bottomed flask and rinse the Erlenmeyer
flask with 62 mL of distilled water and add this rinse carefully to the round-bottom flask. Plug
the side-arm of the flask with a cork, add boiling chips, and set up the steam distillation
apparatus. Steam-distill the mixture until no more oily drops come over with the distillate (60-75
mL of distillate).
Saturate the distillate with 18.5g of sodium chloride in a separatory funnel and extract the
oil from the salt solution. Add 12.3 mL of ether to the salt solution and extract the latter before
adding this extraction to the oil. Dry the combined solutions over anhydrous sodium sulfate.
Filter the solution through filter paper in a glass funnel into a 125 mL Erlenmeyer flask. Rinse
the remaining solid on the filter paper with 6-12 mL of ether.
Remove the ether layer by distilling the solution in a steam bath. Set up the simple
distillation apparatus and collect the fraction that starts boiling at 1550C. Analyze the product via
infrared spectroscopy to check for functional groups (e.g. hydroxyl group) and thus determine if
the product was successfully produced.
Compound MW Density Amt. Used # Moles MP/BP (oC)
Cyclohexene 82.14g 0.81 g/ml 12.3 mL 0.12 -103.7/83.3
Cyclohexanol 100.16g 0.96 g/ml 12g 0.12 25/161
Calculation of the limiting reagent
This reaction would not have a limiting reagent.
Calculation of the theoretical yield
One mole of cyclohexene reacts to form one mole of cyclohexanol.

1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻10 → 1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻12 𝑂
0.12 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻10 →
0.12
1
× 1 = 0.12 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻12 𝑂
1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻12 𝑂 → 100.16𝑔 𝑜𝑓 𝐶6 𝐻12 𝑂
0.12 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻12 𝑂 →
0.12
1
× 100.16 = 12𝑔 𝑜𝑓 𝐶6 𝐻12 𝑂
ii. Cyclohexanone from Cyclohexanol 29
Scale: 0.12 mole (12.5 mL; 12g) of cyclohexanol.
Procedure:
Add 12.5 mL of cyclohexanol to a 250 mL Erlenmeyer flask that contains 40 mL of
distilled water. Then, add 100 mL of sodium dichromate solution to the flask containing the
cyclohexanol, stir the solution whilst keeping the temperature between 55 and 600C for 15
minutes and watch for the color change from orange-brown to dark blue-green.
Wait another 15 minutes to allow for additional reaction to take place before transferring
the reaction mixture to a 500 mL round-bottomed flask using a glass funnel. Rinse the
Erlenmeyer flask with 150 mL of distilled water and add this rinse to the round-bottomed flask.
Add boiling chips to the flask before distilling the mixture via steam distillation and collect 100
mL of distillate in a graduated cylinder.
Transfer the distillate to a 250 mL Erlenmeyer flask, add 20g of solid sodium chloride
and swirl the mixture to dissolve the salt. Pour the mixture into a separatory funnel, shake and

vent, and separate the layers (organic-upper/aqueous-lower) into two flasks. Return the aqueous
layer to the separatory funnel and add 40 mL of dichloromethane. Shake and vent the separatory
funnel before draining the dichloromethane layer into the organic flask. Add the aqueous layer to
the aqueous flask. Return the organic layer to the separatory funnel and add an equal volume of
saturated aqueous sodium chloride solution. Shake and vent the funnel again before draining the
dichloromethane layer into a clean, dry flask. Add 8g of anhydrous sodium sulfate to the flask
containing the organic layer and swirl for 5 minutes.
Weigh a 125 mL Erlenmeyer flask and record its mass. Then, decant the liquid into a dry
100 mL round-bottom flask and add boiling chips before distilling via simple distillation. Collect
the first fraction and second fractions (bp 40-600C/bp 60-1400C) in graduated cylinders. Then,
collect the final fraction (bp 150-1550C) in the pre-weighed Erlenmeyer flask.
Save a few drops for infrared spectroscopy. The IR spectrum of the product can be
compared to that of cyclohexanol (e.g. ketone group). Determine the weight of the product and
calculate the percentage yield.
Cyclohexanol 100.16g 0.96 g/ml 12.5 mL 0.12 25/161
Cyclohexanone 98.14g 0.95 g/ml 11.8g 0.12 -31.2/156
One mole of cyclohexanol reacts to form one mole of cyclohexanone.
1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻12 𝑂 → 1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻10 𝑂
0.12 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻12 𝑂 →
0.12
1
× 1 = 0.12 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻10 𝑂

1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻10 𝑂 → 98.14𝑔 𝑜𝑓 𝐶6 𝐻10 𝑂
0.12 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻10 𝑂 →
0.12
1
× 98.14 = 11.8𝑔 𝑜𝑓 𝐶6 𝐻10 𝑂
b. Benzene to Benzaldehyde
i. Synthesis of Bromobenzene 30, 31
Scale: 0.13 mole (11.5 mL; 10g) of benzene.
Procedure:
Add 0.15 mL of pyridine and 11.5 mL of benzene to a 100 mL round-bottomed flask.
Place the round-bottom flask-fitted with a reflux water condenser-in an ice-water bath. At the top
of the condenser, place a glass delivery-tube that leads through a piece of rubber tubing to an
inverted glass funnel, the rim of which dips just below the surface of water in a beaker. This
prevents the bromobenzene from getting "sucked back". The apparatus should not be in sunlight.
Slowly, pour 7.2 mL of bromine down the condenser, and afterwards immediately
replace the delivery-tube. After the initial evolution of bromobenzene, heat the water bath to 25-
30°C for one hour, whilst intermittently shaking the contents of the flask. Finally raise the
temperature of the water bath to 65-70°C for another 45 minutes.
Transfer the dark-colored liquid to a separatory funnel, shake and vent the liquid with an
excess of 10% aqueous sodium hydroxide solution. The heavy lower layer of crude
bromobenzene should become almost colorless. Separate the bromobenzene into a flask. Shake
and vent the bromobenzene with distilled water before extracting it to ensure absence of alkali.

Dry the recovered bromobenze with anhydrous sodium sulfate for 20-30 minutes. Filter the salt
solution directly into a 125 mL distilling-flask via vacuum filtration. Distill the crude
bromobenzene slowly and collect the fraction that starts boiling at 150°C.
Carefully refractionate the distilled liquid of boiling point 150-160°C, by fractional
distillation to obtain pure bromobenzene of boiling point 155-156°C. Save a few drops for
analysis by infrared spectroscopy. In addition, prepare a sample of the product for NMR analysis
to check for functional groups.
Benzene 78.11g 0.87 g/ml 11.5 mL 0.13 5.5/80.1
Bromobenzene 157.01g 1.49 g/ml 20.4g 0.13 -30.8/156
One mole of benzene reacts to form one mole of bromobenzene.
1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻6 → 1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟
0.13 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻6 →
0.13
1
× 1 = 0.13 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟
1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟 → 157.01𝑔 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟
0.13 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟 →
0.13
1
× 157.01 = 20.4𝑔 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟
ii. Preparationof Phenylmagnesium bromide 32, 33, 34, 35

Scale: 0.13 mole (13.4 mL; 20.4g) of bromobenzene.
Procedure:
Weigh out 2.7g of magnesium turnings, mash them in a mortar and place the magnesium
in a 500 mL round-bottomed flask. Clamp the flask securely, with enough space for an ice bath.
Cork the side arm of the flask, and attach the Claisen adapter to the flask. Attach the 250 mL
separatory funnel (addition funnel) to the Claisen adapter directly above the flask, and a reflux
condenser to the other joint of the Claisen adapter. Stopper the addition funnel. To the top of the
West condenser, attach a vacuum adapter packed with anhydrous calcium chloride with a rubber
bulb over its sidearm. See lab textbook for a picture of the assembled apparatus for the Grignard
reaction. 36
Add 13.6 mL of bromobenzene and 54 mL of anhydrous diethyl ether to the separatory
funnel. Run the bromobenzene-diethyl ether solution into the flask. After the mixture is added,
place 81 mL of anhydrous diethyl ether in the separatory funnel.
Mixture will get warm and cloudy and bubbles may form on the magnesium after the
reaction has begun. If no change is observed after a few minutes, try the suggested steps in the
lab textbook. 37 When the mixture turns dark brown and the ether starts to boil, start the water
flowing slowly in the reflux condenser, and add the 81 mL of ether from the separatory funnel. If
the boiling becomes too vigorous, cool briefly in an ice bath until a gentle reflux is obtained.
The reaction is over when refluxing stops and only a few bits of magnesium remain in the
reaction flask. Check the volume of the reaction mixture; if most of the ether has boiled away,
add more anhydrous diethyl ether. Allow the mixture to stand for a few minutes and cool to room
temperature. The Grignard reagent has to be used immediately and therefore cannot be checked
for analyzed for product purification and characterization.

iii. Carbonationof Phenylmagnesium Bromide; Hydrolysis of
ReactionMixture 38, 39, 40
Procedure:
Place an excess of dry ice into a clean, dry 250 mL beaker. Carefully pour the Grignard
reagent onto the dry ice. Rinse the reaction flask with about 10 mL of anhydrous ether and add to
the beaker.
Slowly add 12 mL of 6 M HCl to the beaker and swirl to remove the remnants of dry ice.
Warm the beaker back to room temperature to dissolve any unreacted dry ice. Add an additional
17-19 mL of ether to the beaker, and stir the reaction mixture. You should have two clear,
distinct layers. If any solid is present, add an additional 11 mL of 6 M HCl and stir again. Pour
the contents of the beaker into a clean, 250 mL Erlenmeyer flask. Rinse the beaker with 10–11
mL of ether and add this rinse to the beaker, swirl, and transfer to the flask.
Transfer the reaction mixture in the Erlenmeyer flask to a 250 mL separatory funnel.
Shake and vent several times to mix the layers. Remove the lower aqueous layer, and leave the
upper ether layer in the separatory funnel. Put the aqueous layer in a 125 mL Erlenmeyer flask
(acid layer).
Add 13 mL of 5% NaOH solution to the ether layer in the separatory funnel; shake and
vent several times. Allow the layers to separate, before removing the lower aqueous layer. Save

this layer in a different 125 mL Erlenmeyer flask (basic layer). Perform two more washings with
13 mL portions of 5% NaOH and combine all the NaOH extracts in the same flask. Save the
upper ether layer remaining in the separatory funnel (ether layer).
Add a small amount of decolorizing charcoal to the flask containing the NaOH layers and
heat it gently on a hot plate, whilst stirring, for about 2 minutes to remove traces of ether
dissolved in the aqueous layer.
Using a glass funnel and filter paper, filter the contents of the flask into a clean, 50 mL
beaker. Add 13 mL of water to the flask that contains the NaOH layers and pour this rinse
through the filter paper as well.
Allow the beaker containing the filtrate to cool to room temperature. Add 26 mL of 6 M
HCl to the beaker, whilst stirring. You should observe the formation of the white precipitate of
benzoic acid. Use litmus paper to determine that the solution is acidic. Check the pH by adding a
drop of the solution from the tip of a stirring rod to a piece of blue litmus paper. If the solution is
not acidic, add HCl drop wise whilst stirring until the solution becomes acidic.
Cool the beaker in an ice water bath. Collect the benzoic acid by vacuum filtration on a
Buchner funnel. Add 10 mL of distilled ice water to the beaker, swirl to rinse, and pour over the
solid on the funnel. Repeat with a second 10 mL portion of distilled ice water. Allow the funnel
in a beaker to dry until the next lab period.
Transfer the dry benzoic acid to a dry, pre-weighed weigh boat, and determine the weight
and percent yield of the product. Determine the melting point range and analyze the product via
infrared spectroscopy (e.g. hydroxyl group & ketone group) and 1H NMR to verify that the
product was successfully produced.

Bromobenzene 157.01g 1.49 g/ml 13.4 mL 0.13 -30.8/156
Magnesium 24.31g ------------- 2.7g 0.11 N/A
Phenylmagnesium
bromide
181.31g 1.14 g/mL 20g 0.11 N/A
Benzoic acid 122.12g 1.27 g/mL 13.4g 0.11 122.41/249.2
Calculation of the limiting reagent (1st Reaction)
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑏𝑟𝑜𝑚𝑜𝑏𝑒𝑛𝑧𝑒𝑛𝑒 = 0.13 𝑚𝑜𝑙
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑚𝑎𝑔𝑛𝑒𝑠𝑖𝑢𝑚 = 0.11 𝑚𝑜𝑙
Therefore, magnesium is the limiting reagent. (Least number of moles)
Calculation of the theoretical yield (1st Reaction)
One mole of bromobenzene reacts to form one mole of phenylmagnesium bromide.
1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟 → 1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝐵𝑟 →
0.11
1
× 1 = 0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟
1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟 → 181.31𝑔 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟 →
0.11
1
× 181.31 = 20𝑔 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟
Calculation of the limiting reagent (2nd Reaction)
Calculation of the theoretical yield (2nd Reaction)
One mole of phenylmagnesium bromide reacts to form one mole of benzoic acid.
1 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟 → 1 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂2
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻5 𝑀𝑔𝐵𝑟 →
0.11
1
× 1 = 0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂2
1 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂2 → 122.12𝑔 𝑜𝑓 𝐶7 𝐻6 𝑂2
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂2 →
0.11
1
× 122.12 = 13.4𝑔 𝑜𝑓 𝐶7 𝐻6 𝑂2

iv. Reduction of Benzoic acid to Phenyl methanol 41
Scale: 0.11 mole (10.6 mL; 13.4g) of benzoic acid.
Procedure:
Add 15 mL of BF3·Et2O/THF, 13.4g of benzoic acid and 25 mL of NaBH4/THF to a 250
mL Erlenmeyer flask. Set up the refluxing apparatus and reflux the mixture until TLC
monitoring shows complete consumption of the substrate. Cool the reaction mixture to 0 ºC
using an ice bath and quench with 10 mL of distilled water, whilst keeping the temperature at 10
ºC. After 10 minutes, cool the mixture in an ice bath to reduce the pressure before removing the
THF via distillation in a steam bath. Add 15 mL of anhydrous diethyl ether, and stir the mixture
for an hour.
Add this mixture to a separatory funnel, shake, and vent and separate the layers. Decant
the organic layer back into the separatory funnel and wash with brine (aqueous NaCl) before
extracting the organic layer again. Dry the organic layer over anhydrous magnesium sulfate, then
cool within an ice bath to reduce the pressure before removing the solvent via vacuum filtration.
The residue can be purified by SiO2 chromatography to give pure benzyl alcohol
(colorless liquid). The product can then be analyzed via infrared spectroscopy (e.g. hydroxyl
group), 1H NMR or 13C NMR to verify that is has been successfully produced.

Benzoic acid 122.12g 1.27 g/mL 13.4g 0.11 122.41/249.2
Benzyl alcohol 108.14 1.04 g/mL 12g 0.11 -15.2/205.3
One mole of benzoic acid reacts to form one mole of benzyl alcohol.
1 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂2 → 1 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻8 𝑂
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂2 →
0.11
1
× 1 = 0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻8 𝑂
1 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻8 𝑂 → 108.14𝑔 𝑜𝑓 𝐶7 𝐻8 𝑂
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻8 𝑂 →
0.11
1
× 108.14 = 12𝑔 𝑜𝑓 𝐶7 𝐻8 𝑂
v. SJR Oxidation of Phenyl methanol 42
Scale: 0.11 mole (11.5 mL; 12g) of phenyl methanol.
Procedure:
Transfer 12g of dry silica gel to a 250-mL round-bottomed flask containing a magnetic
stirring bar and fitted with a rubber septum. Add 3.6 mL of Jones reagent (CrO3/aq. H2SO4)
slowly to the vigorously stirred silica gel and keep stirring until an orange powder is obtained.
Add 50 mL of anhydrous diethyl ether to the round-bottom flask.

Add 12g of benzyl alcohol and 12 mL of ether to a 125 mL Erlenmeyer flask and transfer
the solution slowly through the rubber septum to the stirred heterogeneous mixture. The orange
SJR should turn dark green/brown immediately. TLC monitoring should indicate complete
disappearance of the starting benzyl alcohol after 10 minutes. Filter the reaction mixture through
a glass funnel with filter paper and wash the residue with 100 mL of ether, adding the rinse to the
filtrate.
Remove the solvent from the solution via vacuum filtration to collect a colorless oil of
pure benzaldehyde. The product can be verified for its purity by NMR and IR analysis.
Phenyl methanol 108.14 1.04 g/mL 12g 0.11 -15.2/205.3
Benzaldehyde 106.1g 1.04 g/mL 11.7g 0.11 -26/178.1
One mole of phenyl methanol reacts to form one mole of benzaldehyde.
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻8 𝑂 →
0.11
1
× 1 = 0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂
1 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂 → 106.1𝑔 𝑜𝑓 𝐶7 𝐻6 𝑂
0.11 𝑚𝑜𝑙 𝑜𝑓 𝐶7 𝐻6 𝑂 →
0.11
1
× 106.1 = 11.7𝑔 𝑜𝑓 𝐶7 𝐻6 𝑂
c. Aldol ReactionSynthesis of 2, 6-Bis (benzylidene) cyclohexanone
43, 44, 45, 46, 47
The Aldol reaction is a condensation reaction between two carbonyl compounds, one of
which has to contain a hydrogen atom α to its carbonyl group. One of the carbonyl compounds is

converted into the corresponding enol/enolate anion which is catalyzed by acid/base. Acidic
aldol reactions occur through an enol and basic aldol reactions through an enolate. The
enol/enolate anion undergoes nucleophilic addition to the electrophilic carbonyl group of the
second carbonyl compound. In this laboratory experiment, the base catalyzed aldol condensation
(with loss of water) of benzaldehyde with cyclohexanone is being performed via the enolate
anion.
Scale: 0.0051 mole (1 mL; 0.5g) of cyclohexanone and 0.0094 mole (1 mL; 1g) of benzaldehyde.
Procedure:
Transfer 1g of benzaldehyde and 0.5g of cyclohexanone to a small test tube and stir to
mix the liquids together. Add 0.2g of solid NaOH to the test tube and continue stirring until the
mixture becomes solid and afterwards allow the mixture to stand for 15 minutes at room
temperature. Add 8 mL of 10% aqueous HCl solution and use a stirring rod to suspend the solid
in the HCl solution. Make sure the solution is acidic by placing a drop of the solution onto blue
litmus paper using a stirring rod. If the solution is not acidic add another 8 mL of 10 % aqueous
HCl solution.
Isolate the crude product by vacuum filtration. Use the stirring rod (if necessary) to
transfer the pasty solid to the filter paper in the Buchner funnel. Wash the solid with 5-10 mL of
cold distilled water, air dry the crude product for 10 minutes, and weigh it in a weigh boat.

Recrystallize the crude 2, 6-bis (benzylidene) cyclohexanone in a 6" test tube using 15-20
mL of a hot 90% ethanol/10% water mixture. Isolate the recrystallized 2, 6-bis (benzylidene)
cyclohexanone by vacuum filtration, wash the residue with 10 mL of cold 90% ethanol/10%
water solution, and air dry it. Determine the mass and melting point of the recrystallized 2, 6-bis
(benzylidene) cyclohexanone and also analyze it by IR and NMR to determine product purity
and to check for functional groups.
Cyclohexanone 98.14g 0.95 g/mL 0.5g 0.0051 -31.2/156
Benzaldehyde 106g 1.04 g/mL 1g 0.0094 -26/178.1
2, 6-bis (benzylidene)
cyclohexanone
274g ------------- 1.4g 0.0051 118-119/N.A
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑐𝑦𝑐𝑙𝑜ℎ𝑒𝑥𝑎𝑛𝑜𝑛𝑒 = 0.045 𝑚𝑜𝑙
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑏𝑒𝑛𝑧𝑎𝑙𝑑𝑒ℎ𝑦𝑑𝑒 = 0.047 𝑚𝑜𝑙
Therefore, cyclohexanone is the limiting reagent. (Least number of moles)
One mole of cyclohexanone reacts to form 1 mole of 2, 6-bis (benzylidene)
cyclohexanone.
0.045 𝑚𝑜𝑙 𝑜𝑓 𝐶6 𝐻10 𝑂 →
0.045
1
× 1 = 0.045 𝑚𝑜𝑙 𝑜𝑓 𝐶20 𝐻18 𝑂
1 𝑚𝑜𝑙 𝑜𝑓 𝐶20 𝐻18 𝑂 → 274𝑔 𝑜𝑓 𝐶20 𝐻18 𝑂
0.045 𝑚𝑜𝑙 𝑜𝑓 𝐶20 𝐻18 𝑂 →
0.045
1
× 274 = 12𝑔 𝑜𝑓 𝐶20 𝐻18 𝑂

4. Budget
Compounds Cost($) Compounds Cost($)
Benzene (100 mL) 42.90 Mg (100g) 43.90
Cyclohexene (100 mL) 28.10 (CH2Br)2 (5g) 27.00
Sodium Chloride (25g) 31.40 Dry Ice (50 lbs.) 30.00
Sodium Chloride (1 L) 43.20 Charcoal (500g) 32.80
Anhydrous diethyl ether
(100 mL)
40.00
BF3 (100 mL) 45.60
Na2Cr2O7 (500 mL) 9.85 THF (100 mL) 54.60
Dichloromethane (100 mL) 41.50 NaBH4 (25g) 61.20
Sodium Sulfate (500 g) 49.50 Silica gel (250 g) 44.20
Sulfuric Acid (100 mL) 100.50
Jones reagent
(25 mL)
93.60
Pyridine (100 mL) 89.00 MgSO4 (500g) 70.00
Bromine (100g) 83.00 HCl (25 mL) 30.80
NaOH (500 mL) 22.50 Sand (1kg) 64.30
TotalCost:$1, 179.45 US

5. References
1. Rahman, A.; Ali, R.; Yurngdong, J.; Kadi, A. A Facile Solvent Free Aldol Reaction:
Synthesis of α, α’-bis-(Substituted-benzylidene) cycloalkanones and α, α’-bis-
(Substituted-alkylidene) cycloalkanones. Molecules. 2012, 17, 571-583.
2. Motiur Rahman, A.; Jeong, B.; Kim, D.; Park, J.; Lee, E.; Jahng, Y. A facile synthesis of
α,α′-bis(substituted-benzylidene)-cycloalkanones and substituted-benzylidene
heteroaromatics: utility of NaOAc as a catalyst for aldol-type reaction. Tetrahedron.
2007, 63, 2426-2431.
3. Amoozadeh, A.; Rahmani, S.; Dutkiewicz, G.; Salehi, M.; Nemati, F.; Kubicki, M. Novel
Synthesis and Crystal Structures of Two α, α′-bis-Substituted Benzylidene
Cyclohexanones: 2, 6-Bis-2-nitro (benzylidene) cyclohexanone and 2, 6-Bis-4-methyl
(benzylidene) cyclohexanone. Journal of Chemical Crystallography. 2011, 41, 1305-
1309.
4. Ref 1; pp 571-583.
5. Dou, J.; Wei, X.; Tang, X.; et al. Liquid Crystal and Rheological Behavior of 2, 6-Bis
(benzylidene) cyclohexanone. Journal of Dispersion Science & Technology. 2011, 32,
329-334.
6. Ref 1; pp 571-583.
7. Ref 1; pp 576.
8. Addison, A. Techniques and Experiments for Organic Chemistry, 6th edition.; University
Science Books: Virginia, 1998; pp 371-372.
9. Coleman, G. H. Laboratory manual of organic chemistry: experiments on a semimacro
scale.; Prentice-Hall: New York, 1891; pp 39.

10. Ayorinde, F. O.; Feldman, M.; Fortunak, J.; et al. Experimental Organic Chemistry,
2014-2015 edition.; Academx Publishing Services, Inc: Massachusetts; pp 150-151.
11. Mann, G. F.; Saunders, C. B. Practical Organic Chemistry, 3rd edition.; Longman:
London, 1952.
12. Rhodium Site Archive. Synthesis of Bromobenzene.
https://www.erowid.org/archive/rhodium/chemistry/bromobenzene.html (accessed March
29, 2015).
13. Portland Community College Department of Chemistry. Experiment 3 Preparation of
Benzoic Acid. http://spot.pcc.edu/~chandy/242/PreparationofBenzoicAcid.pdf (accessed
March 21, 2015). pp 1-9.
14. Towson University Department of Chemistry: Wells, J. D. The Grignard Reaction:
Preparation of Benzoic Acid.
http://pages.towson.edu/jdiscord/www/332_lab_info/332labsirpmr/expt3grignard.pdf
(accessed March 29, 2015). pp 1-7.
15. Ref 10; pp 178-180.
16. Bruice, P. Y.; Organic Chemistry, 6th edition. Chapter 11, section 11.8; Prentice Hall:
New York, 2010.
17. Ref 13; pp 1-9.
18. Ref 14; pp 1-7.
19. Ref 16.
20. Cho, S.; Park, Y.; Kim, J.; Falck, J. R.; Yoon, Y. Facile Reduction of Carboxylic Acids,
Esters, Acid Chlorides, Amides and Nitriles to Alcohols or Amines Using
NaBH4/BF3·Et2O. Bull. Korean Chem. Soc. 2004, 25, 407-409

21. Rhodium Site Archive. Silica Gel Supported Jones Reagent (SJR): A Simple And
Efficient Reagent For Oxidation Of Benzyl Alcohols To Benzaldehydes.
https://www.erowid.org/archive/rhodium/chemistry/alcohol2aldehyde.sjr.html (accessed
March 21, 2015).
22. Ref 10; pp 190-193.
23. Ref 1; 571-583.
24. Ref 2; 2426-2431.
25. Ref 3; pp 1305-1309.
26. Ref 5; 329-334.
27. Ref 8; pp 371-372.
28. Ref 9; pp 39.
29. Ref 10; pp 150-151.
30. Ref 11.
31. Ref 12.
32. Ref 10; pp 178-180
33. Ref 13; 4-5.
34. Ref 14; 4-6.
35. Ref 16.
36. Ref 10; pp 179.
37. Ref 10; pp 180.
38. Ref 13; pp 6-7.
39. Ref 14; pp 6-7.
40. Ref 16.

41. Ref 20; pp 407-408.
42. Ref 21.
43. Ref 10; pp 190-193.
44. Ref 1; 571-583.
45. Ref 2; 2426-2431.
46. Ref 3; pp 1305-1309.
47. Ref 5; 329-334.

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