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Exp’t 494: Preparation of fluorenol, and 9-chlorofluorene and difluorenylidene: A multi-step synthesis from fluorenone

R. D. Minard,, Bellamarie Bregar and other students from Spring ’01 Honors Organic Chemistry Rev 9/2/03

Introduction:In place of the standard TLC and column chromatography labs, you will do a 4-step synthesis of difluorenylidene.

difluorenylidene9-chlorofluorenefluorenolfluorenonefluorene

baseHClNaBH4

NaOH

O2 (air)H ClH OHO

1 2a 2b 3

sulfolanePhase

TransferCatalyst

Synthetic step 2a - The conversion of fluorenone to fluorenol requires a reduction of a ketone carbonyl to an alcohol. These aretypically done with hydride reducing agents such as lithium aluminum hydride (LiAlH4) or sodium borohydride (NaBH4). Theadvantage of the latter is that it is only slowly decomposed by water at neutral or basic pH. The fluorenol is isolated in crude wetform and used immediately in reaction 2b because of its tendency to air oxidize back to fluorenone.Synthetic step 2b.- The alcohol group in fluorenol is replaced by chlorine using an SN1 substitution reaction. The 9-chlorfluorene iseasily purified and is stable against air oxidation.As with reaction 1 TLC and GC can be used to follow the progress of these reactions or check the purity of the final product.

Synthetic steps 2a and 2b. Fluorenone will be converted to 9-chlorofluorene. The procedure for the sodium borohydride reduction isin Ref 6 of your difluorenylidene J. Chem article (Experimental Organic Chemistry, Durst and Gokel, 1980, pp 410-412. The crudealcohol should be examined by TLC (or GC) to ascertain that all the ketone has been reduced to the alcohol and if so, it will be usedwithout purification and converted to 9-chlorofluorene by reaction with conc. HCl.Let the 9-chlorofluorene dry thoroughly and weigh to calculate overall yield from fluorenone. Take a mp.

ExperimentalFluorenol2

The reduction of fluorenone via sodium borohydride

500 mg fluorenone50 mg NaBH45 mL methanol10 mL cold H20

In a 50-mL Erlenmeyer flask, dissolve the fluorenone in MeOH by stirring with a magnetic stir bar. You may need to warm thesolution on a heating mantle (no sand) to dissolve all the ketone. Allow the solution to come to room temperature. This step is veryimportant, because addition of sodium borohydride to warm methanol could lead to a fire or small explosion.

Weigh the sodium borohydride in a shorty vial. While stirring magnetically, add the reducing agent slowly in about 4 portions. Onceadded, swirl vigorously to dissolve all the sodium borohydride. This reaction should take around 20 minutes. The yellow color fromthe fluorenone should fade completely from the solution. If it does not add about 25% more NaBH4.

Once the reaction has finished, add the cold H20. Clamp the flask and heat the solution on a heating mantle (no sand) with stirringuntil it just begins to boil and maintain a gentle boil for 10 min to assure the destruction of all NaBH4. Move the flask up if boilingbecomes too vigorous.

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Allow the solution to cool to room temperature and break up any lumps with a spatula. Collect your crystals by vacuum filtration on aBuchner funnel and wash with a few mL of cold H2O, pressing liquid out of the solid with a spatula. Promptly move on to thesynthesis of 9-chlorofluorene. If you leave the fluorenol sitting for too long, air will re-oxidize it back to the ketone. Take about 30mg, dry in vacuum (bell jar), and obtain an NMR and mp as quickly as possible.

9-chlorofluorene3

Figure 14: The chloro substitution of fluorenol500 mg fluorenone starting in 2a6 mL 12M (concentrated!) HCl35 mL cold distilled H20

Wear gloves while measuring out the conc. HCl and when filtering the reaction product!

Transfer your fluorenol from the Buchner funnel into a 100-mL 19/22 round-bottom flask from your blue kit, add a 1” stir bar andclamp in a heating mantle above a mag. stirrer. Add the HCl to the 100-mL flask. Insert a condenser (don’t bother to connect upcooling water hoses) and bring the reaction to a gentle boil. While stirring, continue boiling gently for 15 minutes.

Remove the heating mantle and stir and cool the reaction back down to room temperature. You should see some sticky material on thewalls of the flask.

Once cooled, add the cold H20. Let the reaction stir for a period of five minutes. 9-chlorofluorene is yellowish in color and shouldappear in compact crystals in the flask. Filter over a Buchner or Hirsh funnel using your microspatula with the broad end bent toscrape the crystals from the wall. Allow to dry until the next lab period.

Spectral analysis: Team up with 3 other people and each one obtain one of the following spectra.

1. IR of fluorenone2. NMR of fluorenol3. GC-MS of 9-chlorofluorene4. UV/Vis of difluorenylidene (in ethanol)

Difluorenylidene3

Figure 15 : The dimerization of difluorenylidene

Weigh your 9-chlorofluorene and calculate a percent yield. To ascertain that you correctly synthesized the product, you may want totake a melting point or run GC-MS on the sample. If your sample looks good, proceed.

Scale up the JCE procedure using 200 mg of the starting 9-chlorofluorene.

You may need to warm up the sulfolane to get it into solution. Run the jar under warm water, and then measure out the quantity youneed. Add the sulfolane to the 9-chlorofluorene. Dissolve all the solid by slightly submerging your flask into a beaker full of warmwater.

The reaction mixture should turn very dark orangish in color. Let the reaction sit for 20 minutes. Add the scaled amount of distilledwater and mix it thoroughly by swirling the contents. A dark orange solid should appear in the flask. Fliter off the product carefullywith a Hirsh funnel. Wash it thoroughly with H20.

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Transfer the filtered compound to a beaker. Dissolve it in a very small amount of dichloromethane. Add the EtOH. Mix the reactioncarefully. Allow the EtOH and dichloromethane to evaporate off until your next lab period.

The reaction may give you a multitude of bizarre by products that may come out of solution before the difluorenylidene. The compundyou want is very red in color. Excess by products, as shown below, are orangish and yellow in color. See figure 2

Figure 16: Difluorenylidene and by-products

Results and Disscussion:

The overall experimental yield of oxidized fluorene was 90 percent. From this, a complete reduction of all the fluorenonewent very cleanly: all the yellowish fluorenone color was lost in the prepared fluorenol. Yields of 9-chlorofluorene were muchsmaller, only 45 percent from the original fluorenone amount. The amount of 9-chlorofluorene lost in by products was quite obviousdue to the small yield of difluorenylidene being only 14 percent.

Melting points of the compounds were fairly accurate. Fluorenone’s literature melting point is 82-85 C. The experimentalvalue was 70-72. In the GC-MS purity check of fluorenone, a large toluene peak was detected and the suspected melting pointdepressor. Although no melting point was recovered on the fluorenol, the fluorenol was very white in color and showed no yellowimpurities, suspects of incomplete reduction. The literature value for 9-chlorofluorene is 93-94 C. Experimentally, the value wasslighty depressed to 89-91. An inadequate drying period could have caused the compound to be “wet” which would also depress themelting point.

Through GC-MS runs, each compound’s identity was ascertained. Figures 10, 11 and 12 show the spectrums for each of themain synthetic steps. GC-MS was not run on the 9-chlorofluorene.. because I’m smart like that.

A number of by products came out of the final dimerization reaction. GC-MS was run on the outside wall of the beakershown in figure 10 to see what the orangish and yellow products could possibly be. Some interesting peaks were said to be suchcompounds as 2,7-dichloro-9-fluorenone, 10, 11,12,13, tetrahydro-benzotriphenylene, and 1,1-biphenyl-2-methanol.References:

1. Minard, Robert, Oriskovich, Tracy, “Column Chromatopgraphy” Lab Guide for Chem 36. 36B, 36H: Introductory OrganicLab, pg. 110-111

2. Durst, Gokel, Experimental Organic Chemistry, 2nd Ed. Pg 405-4083. Greenberg, Fred H, “Microscale Preparation of Difluorenylidene and trans-2,3-Dibenzoylspiro[cyclopropane-1-9’-fluorene]”

Journal of Chemical Education, Vol. 73, No. 11, November 1996, pg 1043-1045