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Synthesis of a tetracarbaldehyde; 5,5',5'',5'''-(benzene-1,2,4,5-tetrayl)tetrakis(thiophene-2-carbaldehyde)

SyntheticPage 870
DOI: 10.1039/SP870
Submitted Nov 28, 2018, published Dec 26, 2018
Kathryn Allen (, Liam Schroeder (
A contribution from Allen Group @ MU of PA

			Reaction Scheme: <img src="/images/empty.gif" alt="" /><img src="/images/empty.gif" alt="" /><img src="/images/empty.gif" alt="" />Synthesis of a tetracarbaldehyde<img src="/images/empty.gif" alt="" /><img src="/images/empty.gif" alt="" /><img src="/images/empty.gif" alt="" />

Chemicals Used

1,2,4,5-tetrakis(5-bromothiophen-2-yl)benzene, see ChemSpider Synthetic Pages 872
N-Butyl lithium (2.0 M in cyclohexane)
Dimethylformamide, anhydrous 99.8%
Tetrahydrofuran, anhydrous, contains 250 ppm BHT as inhibitor, used as is >99.9%


A three-necked round bottomed flask equipped with condenser and stir bar was dried in an oven at 130°C overnight, then quickly sealed with three septa and actively purged with nitrogen gas for 20 minutes. Anhydrous tetrahydrofuran (24 mL) and 1,2,4,5-tetrakis(5-bromothiophen-2-yl)benzene (0.206 g, 0.285 mmol, 1 eq.) were added to the flask under nitrogen and the flask was cooled to -78°C in a dewar of dry ice/acetone. N-butyllithium (0.599 mL, 1.2 mmol, 4.2 eq.) was added drop-wise and the reaction was stirred for 15 minutes before warming to 0°C. After monitoring the reaction by TLC (10% ethyl acetate/hexanes, starting material Rf = 0.64, lithiated intermediate Rf = 0.51) to ensure the lithiation was complete (~30 min.), the reaction was then cooled down to -78°C again and dimethylformamide (0.3 mL, 3.87 mmol, 14 eq.) was added to quench. The quench with DMF was monitored through TLC of the reaction mixture (10% ethyl acetate/hexanes; product does not move off baseline). When the DMF had reacted (~1 hr.), the reaction was quenched with water. The tetrahydrofuran was evaporated off and the residue was dissolved in methylene chloride and washed with water and brine. The organic layer was then dried with sodium sulfate and concentrated under reduced pressure. The suspension was taken up in hot methanol, cooled and vacuum filtered through a Buchner funnel to yield the product as a yellow-orange powder (0.090 g, 0.174 mmol, 61% yield).

Author's Comments

Care should be taken when working with n-butyllithium. Always ask your advisor before handling this material. n-BuLi was handled using a sure seal bottle under nitrogen after safety training and under a PI's direct supervision. Ensure that the syringe used to handle the n-BuLi is long enough to reach the bottom of the bottle when the bottle is clamped in the upright position. Be sure nitrogen is flowing freely into the bottle via needle and nitrogen line. This procedure is not meant to educate students on proper handling of n-BuLi; please consult your advisor for the correct protocol to handle organolithiates in your laboratory.
TLC of the reaction mixture at each stage was prepared by withdrawing a small aliquot by syringe and needle, quenching in wet ethyl acetate and spotting directly on a TLC plate. 
A large excess of DMF ensured the reaction quenched in minutes rather than hours. DMF was easily partitioned away with aqueous washes.
The authors thank Dr. Daniel Ralston for DART MS collection.

The authors thank the NSF REU program at James Madison University for funding (CHE 1757874).


1H NMR (400 MHz, CDCl3): δ 9.890 (s, 4H), 7.722 (s, 2H), 7.668 (d, 4H, J = 3.86 Hz), 7.072 (d, 4H, J = 3.86 Hz)
13C NMR (400 MHz, CDCl3): δ 182.871, 149.560, 145.067, 136.401, 133.794, 133.682, 129.325.
Mass Spec: Calculated: 518.6340 g/mol Observed: 517.6280 g/mol
IR: 1656 cm-1 (C=O)

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Keywords: lithiation

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