Cindy Lee
1041791
Synthesis of Azulene
March 9, 2006-April 6, 2006
Introduction & Background
Azulene is a simple, beautiful, blue compound with many unusual properties (Lemal et. al.,1999). It is also quite expensive (Alrich 2006: $194 /g, 99% pure). This aromatic hydrocarbon is an isomer of naphthalene. However, it is less stable than naphthalene because it has less resonance structures.
The fundamental difference between the two is that naphthalene is an alternant hydrocarbon, while azulene is a non-alternant. This results in azulene not having “mirror related” molecular orbitals and a dipole moment, from non-uniform charge distribution.
The reason azulene is blue, is also due to the fact it is non-alternant. Though azulene’s HOMO and LUMO gap are close to that of anthracene, which is colourless, it isn’t colourless. Since azulene is non-alternant, the HOMO and LUMO are not mirror-related so the atomic orbital coefficients in these two orbitals differ greatly at many of the skeletal atoms. The gap between the HOMO and LUMO is smaller than anticipated because promotion of one of the pairs of electrons from the HOMO to the LUMO increases the average distance between the members of the pair, which reduces the mutual repulsion of that pair considerably and a lower transition energy results. This lower transition energy correlates to blue light.
In this experiment, we plan to synthesize azulene by an adapted synthesis of Copland, Leaver, and Menzies. This involves preparation of the intermediates 3,4-dibromotetrahydrothiophene and 6-dimethylaminofulvene. 3,4-dibromotetrahydrothiophene is then reacted with strong base to form thiophene-1,1-dioxide. This thiophene and the 6-dimethylaminofulvene are reacted together to form azulene. Each intermediate and the product were analyzed by physical properties, infrared, and 1H NMR spectroscopy. We were successful in synthesizing azulene, with an overall yield of 114% (end product contained some impurities).
References
Synethesis of Azulene, a Blue Hydrocarbon. David M. Lemal and Glenn D. Goldman, Journal of Chemical Education (1999) 65: 923
Chemistry 361/363 Laboratory Manual 2005-2006 Edition L.M. Browne pp 187-198
Organic Chemistry Experiments Chemistry 161/163 2002-2003 Edition L.M. Browne pp 317-322
Chemfinder
SDBS
NIST Chem Webbook
Balanced Equations
(1)
(2)
(3)
(4)
(5)
Overall Mechanism Scheme
Page 1 of 18
Cindy Lee
1041791
Table 1. Table of Reagents
Compound / MW(g/mol) / wt/vol
used / moles
mmol / density
g/mL / mp/bp
oC / Hazardous Properties
2,5-dihydrothiophene dioxide / 118.1502 / 5.0g / 42 / mp=64.65
alumina / 101.96128 / column / 3.97 / mp=2030
bromine / 159.82 / 6.8g / 43 / 3.102 / bp=59.5 / highly toxic, oxidizer
chloroform / 119.38 / 1.500 / bp=61-62 / highly toxic
cyclopentadiene / 66.1024 / 2.7g / 41
dimethylformamide diethyl acetal / 147.2168 / 4.88g, 5.45mL / 41 / 0.859 / bp=130-133 / moisture sensitive
dimethylformamide dimethyl acetal / 119.164 / 5.45mL / 41 / 0.89 / bp=104 / flammable
ethanol (95%) / 46.07 / 0.816 / bp=78 / flammable
ethyl acetate / 88.11 / 0.9 / bp=76-77 / flammable, irritant
hexane / 86.18 / 0.659 / bp=69 / flammable, irritant
iodine / 253.81 / mp=133 / corrosive, highly toxic
nitrogen / 28.0134 / mp=-209.95
bp=-195.86
pentane / 72.1498 / 0.626 / mp=-129.7
bp=36.1 / flammable
petroleum ether / 0.640 / bp =35-60 / flammable, toxic
potassium hydroxide / 56.11 / corrosive, toxic
anhydrous tetrahydrofuran / 72.11 / 80mL / 0.868 / bp=67 / flammable, irritant
Page 1 of 18
Cindy Lee
1041791
Part 1: Preparation of 3,4-Dibromotetrahydrothiophene
Objective:
- React bromine and 2,5-dihydrothiophone dioxide to produce 3,4-dibromotetrahydrothiophene
- Recover the product and wash with chloroform.
Mechanism:
Procedure and Observations
Procedure / Observations-Fill balloon with N2 to ~20cm in diameter, store on top of a small flask
-Dry a 50 mL 3-neck flask, stir bar, dropping funnel, condenser
-Take apparatus to fumehood where the reaction will be carried out
-Charge an addition funnel with 6mL CHCl3 and 6.8g Br2 (0.043mol)
-Introduce 8mL CHCl3 into the 3-neck flask and 5.0g (0.042mol) 2,5-dihydrothiophene dioxide
heat and stir
add Br2 over 30-45 minutes
reflux for 2 hours
cool to room temperature then on ice
-Filter bright red mixture with sintered glass funnel
wash with chloroform until crystals are colourless
(if necessary, concentrate on rotovap and recrystallize the product from CHCl3)
-combine crystals and dry with suction in the Buchner funnel
(more dibromide can be recovered from mother liquor if desired)
Characterization
-physical properties
-IR
-1H NMR
-Store product in foil-wrapped labeled vial in the fridge in W1-03 / March 9, 2006
-filled balloon with a line in the fumehood
-flame-dried glassware
-greased joints
-added 8mL of CHCl3 in 3-neck flask
-added 4.952g of butadiene sulphone to flask
-stirred to dissolve (heated with rheostat at 20)
-added 6mL of CHCl3 to addition funnel
added 2.2mL of Br2 (solution was an orange colour)
-slowly added ~1 drop/second over 40 minutes
-(red) crystal crashed out after addition was completed
-crystals were transferred to a sintered glass funnel (added 1mL of CHCl3 to dissolve)
mixed to a suspension
turned on vacuum
washed with CHCl3 until crystals were white (small yellow crystals in the white crystals were washed but didn’t turn white)
-white solid cystals
- yield: 29.192g- 21.931g=7.261g
-dissolved in CHCl3 and did a film cast
-dissolved end of scoopula amount in ~0.5mL CDCl3
Product – Properties And Yield
Balanced Equations and Theoretical Yield Calculations
+
n = 42 mmol* / n = 43 mmol / n = 42 mmolm = 5.0 g / m = 6.8 g / m (theoretical) = 11.67g
M = 118.1502 g/mol / M = 159.82 g/mol / M = 277.958 g/mol
* 2,5-dihydrothiophene-1,1-dioxide is the limiting reagent
Table 2. Table of Products
Product / MW(g/mol) / Properties Found / Yield
Theoretical / Actual / %
3,4-dibromotetrahydrothiophene / 277.958 / white crystals / 11.67g
(42 mmol) / 7.261g
(26.12mmol) / 62.2
The product 3,4-dibromotetrahydrothiophene was obtained as white crystals after washing with chloroform. The 1H NMR showed that the product was fairly pure with a couple small solvent peaks. The % yield for this reaction was 62.2%.
Characterization
The infrared spectrum of the compound indicates a C-H stretch at about 3015.9 cm-1. There is a peak at 1313.7cm-1, which is part of the sulfone group, (S=O stretch). There are also peaks at 905.4 and 836cm-1which could be the C-S and C-Br stretches.
Table 3 lists and explained the characteristic peaks.
Table 3. IR Data for 3,4-dibromotetrahydrothiophene
Frequency (cm-1) / Intensity / Shape / Assignment / Structure3015.9 / weak / sharp / C-H (sp3)
1313.7 / medium / sharp / S=O
905.4/836.1 / medium / sharp / C-Br or C-SO2-R
The 1H NMR spectrum is fairly clean, with a couple of small solvent peaks, and shows the 3 different hydrogen peaks. The products that are formed are enantiomers, complicating the spectrum. There are each pairs of hydrogen (A, B, and C) are chemically equivalent but not magnetically equivalent. This creates second order coupling, and the multiplicity is too complicated to determined for peak A. Peaks B and C are doublets of doublets. Both have one J value that is large (~14Hz) which correlates to geminal coupling (to proton B or C) and one J value that is smaller (~5Hz) that correlates to vicinal coupling to proton A. The three peaks are shifted downfield (3-5ppm) indicating they are connected to carbons attached to electron withdrawing groups (bromine and sulfone). Table 4 lists the 1H NMR data.
Table 4.1H NMR Data for 3,4-dibromotetrahydrothiophene
Label / (ppm) / Area / Splitting / J (Hz) / Structure and Signal AssignmentA / 4.79 / 2 / multiplet
B / 4.026 / 2 / doublet of doublets / JB,A=5.56 (vicinal)
JB,C=14.52 (geminal)
C / 3.548 / 2 / doublet of doublets / JC,A=5.46 (vicinal)
JC,B=13.84 (geminal)
The 13C NMR only contains two peaks, which shows that the molecule is symmetrical. The two peaks are in the 40-60ppm region indicating the carbons are next to electron withdrawing groups. The sulfone group is more electron withdrawing than the bromine so the more downfield peak would be the C-S carbon. Table 5 lists the 13C NMR data.
Table 5.13C NMR Data for 3,4-dibromotetrahydrothiophene
Label / (ppm) / Type of Carbon / Structure and Signal Assignment1 / 60 / C-S (sulfone)
2 / 46 / C-Br
Discussion and Conclusion
The 1H NMR and infrared spectra showed that 3,4-dibromotetrahydrothiophene was successfully produced. The hydrogens in the 1H NMR spectrum were shifted downfield indicating they were attached to electron withdrawing groups, the bromine and sulfone. The spectrum was not simple to analyze because enantiomer products were formed and there was second order splitting. 1H NMR spectrum was very clean indicating the product was fairly pure. The reaction ran very smoothly and we did not have to reflux the reaction for very long before crystals crashed out. The % yield was 62.2%.
Part 2: Preparation of 6-dimethylaminofulvene
Objective:
- Prepare cyclopentadiene for the reaction. (Carried out by TA)
- React cyclopentadiene with dimethylformamide diethyl acetal to produce 6-dimethylaminofulvene
- Purify 6-dimethylaminofulvene by recrystallization from petroleum ether.
Mechanism:
Procedure and Observations
Procedure / ObservationsCarried out by TA: Preparation of cyclopentadiene
-50mL round-bottom flask, place 10mL dicyclopentadiene and boiling chips
-fit flask with Vigreux column with distillation adapter and thermometer, attach to condenser with vacuum adapter
-cool receiver in ice-salt bath
-protect from atmospheric moisture with drying tube connected to vacuum outlet
-distill very slowly
-store in tightly stoppered flask in freezer
Preparation of 6-dimethylaminofulvene
-dry 25mL round bottom flask, water-cooled condensor
-use nitrogen balloon to flush system with nitrogen
-add 41 mmol of dimethylformamide diethyl acetal (4.88g, 5.45mL)
-quickly add cyclopentadiene (41mmol, 2.7g)
-flush with N2
-heat at a moderate reflux for 3 hours (should turn orange-red)
-TA will put stuff away and store in fridge
Purification
-Rotavap to remove volatiles
-recrystallize from petroleum ether using a steam bath (large volume of petroleum ether may be required)
-yield of yellow crystals is ~1.5g (30%)
Characterization
-physical properties
-IR
-1H NMR
-store in the fridge, in the dark (light sensitive) / March 16, 2006
-assembled 25mL round bottom flask and Vigreux column in the fumehood
-dried with a heat gun
-used nitrogen line in fumehood to flush system
-added 5.45mL of dimethylformamide dimethyl acetal (instead of diethyl acetal)
-added (cold) 3.4mL cyclopentadiene
-heat at ~35 on Variac
-when reluxing, switched from nitrogen line to CaCl2 drying tube
-the reaction was supervised by Leah and everything was taken down by her after ~3 hours and stored in the fridge (in foil)
March 23, 2006
-combined Jason and my reacted solutions (brown-yellow colour)
-rotovap to remove volatiles
-transferred to Erylenmeyer flask (crystals crashed out)
-heated ~300mL of petroleum ether and added to crystals to dissolve (with crushing to break up the crystals)
-black particles didn’t dissolve
-hot gravity filter to remove black particles
-yellow solution as filtrate
-heated on steam bath to reduce volume to ~100mL
cooled to room temp and then ice to induce crystallization (yellow flaky crystals formed)
filtered with a Buchner funnel
-took the filtrate and reduced the volume further (repeated above steps twice)
-yellow flaky crystals
-yield= 10.980g - 9.782g=1.198g
-dissolved in CDCl3 and did a film cast
-dissolved crystals in ~1mL CDCl3 (0.5mL for Jason, 0.5mL for myself)
-wrapped in foil before next step
Product – Properties And Yield
Balanced Equations and Theoretical Yield Calculations
+
n = 41 mmol / n = 41 mmol / n = 41 mmolm = 2.7 g / m = 6.8 g / m (theoretical) = 4.97 g
M = 66.1024 g/mol / M = 147.2168 g/mol / M = 121.2 g/mol
(with partner
4.97 g * 2 = 9.9 g)
*both reactants were the same moles, so they were both limiting.
.
Table 6. Table of Products
Product / MW(g/mol) / Properties Found / Yield
Theoretical / Actual / %
6-dimethylaminofulvene / 121.2 / gold flaky crystals / 9.9g
(41 mmol) / 1.198g
(9.884 mmol) / 12.1
The product 6-dimethylaminofulvene was obtained as gold flaky crystals. The crude product was combine with Jason’s and recrystallized together because the yield for this reaction is normally low, ~30%. Our yield was very low, 12.1%. Unfortunately, as shown by the 1H NMR, the sample was not free of the petroleum ether that was used for recrystallization. (This may have been due to the weak vacuum during recovery of the crystals.)
Characterization
The infrared spectrum showed two characteristic stretches of alkenes, the peak at 3068.1cm-1 is the C-H (sp2) stretch and the peak at 1619.0 cm-1 (and possibly those at 1300 cm-1)is the C=C stretch. There are also unlabeled peaks at about 2900cm-1. 1170 cm-1 is a typical frequency for a C-N stretch of a tertiary amine. Table 7 lists and explains the characteristic peaks.
Table 7. IR Data for 3,4-dimethylaminofulvene
Frequency (cm-1) / Intensity / Shape / Assignment / Structure3068.1 / weak / sharp / C-H (sp2)
~2900 / weak / sharp / C-H (sp3)
1619.0
(1373.3 / 1353.6) / strong / sharp / C=C
1170 / medium / sharp / C-N
Unfortunately, there was no enough sample in the NMR tube so the signal to noise ratio of the 1H NMR spectrum is not very good. There is also some petroleum ether is clearly present. The signal peaks are still visible, but I used Natalie’s spectrum for ease of analysis.
The protons in the 5 membered ring are not chemically equivalent due to the double bond being asymmetrical, so each proton has their own distinct chemical shifts. There are 5 peaks from 6.3-7.2ppm that are a little higher than characteristic chemical shifts of vinylic protons. The compound is not aromatic but the electrons are delocalized around the ring, which may the reason for the higher shift. The farthest downfield peak is a singlet, which is the vinylic proton of the alkene with the amine group attached (only vinylic proton with no neighbours). The other 4 peaks are doublets of doublets of doublets. They couple to their neighbouring protons (ortho J~4Hz, meta J~2Hz). The most upfield peak is a singlet with an integration of 6, which are the protons on the methyl groups of the amine. The chemical shift of this peak is shift downfield slightly, indicating it is close to an electron-withdrawing group (nitrogen). Table 8 lists the 1H NMR peaks.
Table 8.1H NMR Data for 3,4-dimethylaminofulvene
Label / (ppm) / Area / Splitting / J (Hz) / Structure and Signal AssignmentA / 7.2 / 1 / s
B / 6.624 / 1 / ddd / 1.65
2.01
4.76
C / 6.591 / 1 / ddd / 1.83
1.83
4.39
D / 6.448 / 1 / ddd / 2.15
2.15
4.3
E / 6.37 / 1 / ddd / 1.60
2.61
4.21
F / 3.3 / 6 / s
The 13C NMR has 8 peaks indicating the molecule is asymmetrical (there are 8 carbons in the compound). The 6 most downfield peaks are those of the alkenes. The 2 most upfield peaks belong to the methyl groups of the amine; because the molecule is asymmetric, the methyl groups are not chemically equivalent. Table 9 lists the 13C NMR peaks.
Table 9.13C NMR Data for 3,4-dimethylaminofulvene
Label / (ppm) / Type of Carbon / Structure and Signal Assignment1 / 149 / C=C
2 / 126 / C=C
3 / 125 / C=C
4 / 120 / C=C
5 / 117 / C=C
6 / 114 / C=C
7 / 23 / -CH3
8 / 15 / -CH3
Discussion and Conclusion
Though the 1H NMR looked messy due to the signal to noise ratio, the peaks characteristic of 6-dimethylaminofulvene are still present. The spectrum had a lot of other peaks, indicating impurities. These impurities are likely solvents (petroleum ether) and because the compound is light sensitive, there may also be some decomposed product because the sample was exposed to light during the preparation of the NMR sample. The infrared spectrum confirmed the presence of alkene groups and the methyl groups of the tertiary amine.
Hence, we were successful in producing 6-dimethylaminofulvene, which was in the form of gold flaky crystals. My crude product was combined with Jason and purified together by recrystallization to obtain a % yield of 12.1%. This is a low yield, but is typical of the reaction.
Part 3: Preparation of Azulene
Objective:
- Prepare thiophene-1,1-dioxide by reacting 3,4-dibromotetrahydrothiophene (from Part 1) with powdered potassium hydroxide
- React thiophene-1,1-dioxide with 6-dimethylaminofulvene (from Part 2) to produce azulene
- Purify azulene with an alumina column
- Recrystallize azulene.
Mechanism:
Procedure and Observations
Procedure / ObservationsPreparation of Thiophene-1,1-dioxide
-place 2.22g (8.00 mmol) 3,4-dibromotetrahydrothiophene in 3 neck, 100mL round-bottom flask, with stir bar, condenser, drying tube, nitrogen balloon with 3-way adaptor, and glass stopper
-flush system with nitrogen
-add 80mL anhydrous THF
-cool mixture in ice-bath, with stirring
-quickly add 4g (0.1mol) of finely powdered potassium hydroxide
stir vigorously under nitrogen
-monitor reaction by TLC (1:1 hexane: ethyl acetate eluent) visualize with UV lamp and iodine
-when reaction is complete, filter the cold mixture through a filter-aid pad
-use clear, colorless filtrate right away
-250mL round-bottom flask with condenser with nitrogen inlet
-add stir bar and 6-dimethylaminofulvene
-flush system with nitrogen
-add cold thiophene-1,1-dioxide
-stir to dissolve the fulvene, producing a red solution
-note colour change
-reflux for 4 hours
-TA will take down and put away flasks.
Purification
-remove tetrahydrofuran at room temperature with rotavap
-triturate residue with 2mL pentane and place the blue soluntion on top of column
-allow sample to be adsorbed and repeat the procedure with additional very small portions of pentane until solvent is no longer strongly coloured
-elute with pentane, collect only the blue band
-evaporate solvent, weigh the blue crystalline
-recrystallize with very small amount of 95% ethanol
-after cooling on ice, remove mother liquor with pipet, quickly wash crystals with small amount of ice-cold ethanol
-suction to dry
Characterization
-physical properties
-IR
-1H NMR / March 30 , 2006
-filled nitrogen balloon
-added 2.22g of 3,4-dibromotetrahydrothiophene
-added ~4g KOH
-added 80mL THF
-solution turned purple almost immediately after addition of THF
-flush with nitrogen
-stirred vigorously
-monitor reaction by TLC (1:1 hexane: ethyl acetate)
-visualized with UV light
-filtered with Celite-pad, used vacuum to full filtrate through
-the residue was black, the filtrate was a clear yellow solution
-kept cold
-setup flask, stir bar, and condenser with N2 inlet in fumehood
-added the 6-dimethylaminofulvene
-added cold thiophene-1,1-dioxide
-upon addition the solution became red-orange
-after 10 minutes, it was yellow-orange
-Leah supervised the reaction and took everything down and stoppered and placed in the fridge.
-removed THF by rotavap
-dry packing for alumina column:
1)cotton plug
2)alumina
3)pack with pentane
4)sand
-added 2 pipettes of pentane to residue from rotavap: 1 to Jason, 1 to me
-added 4 pipettes of pentane, 2 to Jason, the rest to me, but not all was used for the column
-collected 5 flasks (pentane as eluent):
1)before the blue band (clear)
2)beginning of blue band (light blue)
3)majority of blue band (dark blue)
4)end of blue band (light blue)
5)after blue band (clear)
-checked purity with TLC (pentane as eluent); visualized with UV light
-pooled fractions 2, 3, and 4
-evaporated on rotavap
-blue crystals remained
-did not do recrystallization
-dark blue crystals
-yield = 87.766g – 87.353g = 0.413g
(Jason obtained 0.757g)
-dissolved in CDCl3 and did a film cast for IR
-dissolved in CDCl3 for 1H NMR
Product – Properties And Yield
Balanced Equations and Theoretical Yield Calculations
+
n = 9.884 mmol / n = 7.987 mmol* / n = 7.987 mmolm = 1.198 g / m = 2.22 g / m (theoretical) = 1.024 g
M = 121.2 g/mol / M3,4-dibromo = 277.958 g/mol / M = 128.17 g/mol
*thiophene-1,1-dioxide (assuming reaction from 3,4-dibromotetrahydrothiophene was 100% complete) is the limiting reagent.