Applications of Cursed Chemistry in the Total Synthesis of  Impracticatechol

Frederick Washing: The Reddit Academic Group, Jonathan Mhama: Twisted Street Pub, Ben Dover: The Reddit Academic Group

Abstract: Burnie Urethra’s group have set themselves a Herculean task: the total synthesis of Impracticatechol (1). The highly complicated  structure features a dozen stereocenters and a raft of functional groups including a pentavalent carbon. This malevolent moiety constitutes a significant challenge to the synthetic chemist, as until now, no methodology has been reported pertaining to their  preparation. Herein, we describe an easy and promiscuous protocol for generating pentavalent carbon centers via a one-pot curse-transfer  cyclisation reaction, inspired by r/cursed_chemistry. 

Specific: We may or may not have destroyed a few flasks during the research process. 

Following the amazing discovery of Impracticatechol1(figure 1) by  Urethra et al, we found the challenge of total synthesis to be very  relatable to us and our nightmares, so we decided to take part in the  research process. The first step of the total synthesis has been  explored already, leaving the remaining 41 reactions incomplete. 

Considering the horrid nature of this structure, we consulted r/cursed_chemistry, a highly reliable source of unconventional  reactions and compounds disregarded by chemists of sound mind.

Figure 1: This abomination called Impracticatechol
Figure 1: This abomination called Impracticatechol

Pentavalent carbons (also known as Texas carbons) have been  thoroughly explored by this community, as have highly nitrogenated  structures and many other marvellous examples (figure 2).

Figure 2: Some structures reported by the Reddit group
Figure 2: Some structures reported by the Reddit group

Our research suggested that a heptaazacubane (2) could act as a  sufficiently cursed reactive intermediate which should theoretically be able to perform an intramolecular curse-transfer to generate a pentavalent carbon.

Proposal and optimisation of the reaction conditions In order to make the heptaazacubane intermediate, we proposed to  use the trinitromethyl group as a CN3 fragment that can be installed  via nucleophilic substitution to an alkyl halide (figure 3). The four other nitrogen atoms could be added by a combination of liquid air  (80:20 N2/O2) and hydrazine. We hope that using two nitrogen  sources and the cooling effect of liquid air would stabilise the  heptaazacubane intermediate.

Figure 3: Proposed mechanism for generating pentavalent carbons
Figure 3: Proposed mechanism for generating pentavalent carbons

As such, we have attempted the synthesis of the benzyl  derivative (2) by combining benzyl chloride, hydrazine sulphate and  trinitromethyl-sodium in a flask, the experiment being performed in  the parking lot of our building for safety reasons (scheme 1). By  slowly adding liquid air, nothing really happened. After five minutes,  the flask detonated, and, by asking lab staff to rate the explosion  from 1 to 10, we guess the yield of heptaazacubane was roughly 69%.

Scheme 1: Standard conditions for curse-transfer cyclisation
Scheme 1: Standard conditions for curse-transfer cyclisation

With evidence for a heptaazacubane intermediate in hand, we tested  the intramolecular curse-transfer cyclisation of alkene-chlorides 3– 11 (figure 4), and on intermediate 13 from the Impracticatechol  synthesis. 

Figure 4: The scope of the Curse-Transfer Function
Figure 4: The scope of the Curse-Transfer Function

Results and discussion 

As shown in figure 3, the reaction can work on both end of the double  bond, unless the position is sterically hindered. In the case of small  rings, the presence of an alkyl group gives the possibility of alkyl  hydrogen abstraction which becomes favoured over the pentavalent product. Without it, the reaction doesn’t work for very small rings, as  shown by the low yield of 9

While conducting this research, we have dealt with a number of accidents including detonation, losing a reagent sample and possibly killing a stray cat. One useful piece of information we have discovered is that we now know 1-(2-chloroethyl)-8-methyl-1,2,3,4-tetrahydronaphthalene (12) is not very toxic to humans.

Seeing the great success of our previous reactions, we attempted the cyclisation of precursor 13 by using our standard conditions.

Figure 5: Synthesis of an Impracticatechol precursor
Figure 5: Synthesis of an Impracticatechol precursor

We obtained 14 with a yield of roughly 5%, but the product exhibited hydrolysis and hydrazine-ketone condensation. In order to optimize the conditions, we switched to the less acidic hydrazine HCl in a smaller amount, while also adding more trinitromethane salt. We added 20 mol% of hydroquinol as a mild reductive agent in order to compensate for the missing hydrazine, and a stone we found on the road because we read that some people use clay to catalyse reactions so it might work for us too.2 We were pleasantly surprised to find that the yield of 14 after extraction is 179%, but the other lab team in our building criticised it (they are probably just jealous).

Experimental procedures

The solvents and glassware were provided by our laboratory, the hydrazine salts and hydroquinol were purchased from Ligma-Eldritch, and the chloro-alkenes and trinitromethane salt were obtained from old mate Garry from around the back of the pub. We do not know where 13 came from, but we confirmed its structure by 1H-NMR analysis and a taste test. All of the experiments were performed in our parking lot, hiding behind an improvised plexiglass shield at a 5-meter distance from the flasks.

The first experiment: A 500 mL three-neck flask is filled with 0.02 mol (2.3 mL) of benzyl chloride, 0.04 mol of trinitromethyl sodium (6.92 g), 0.02 mol of hydrazine bisulfate (2.6 g) and 10 mL of benzene. We add a stir bar, an addition funnel and then cover the flask in aluminium foil to prevent photochemical decomposition. The addition funnel is filled with 50 mL of liquid air which is then added dropwise under strong stirring, starting a chronometer and phone camera at this point. After 5 minutes 36 seconds, the flask detonates. The video is present in the supplementary material.

General procedure for the cyclization reaction: 0.02 mol of the chosen reagent is added in a three-neck flask together with 0.03 mol of trinitromethyl sodium (5.19 g), 0.02 mol of hydrazine bisulphate (1.3 g) and 10 mL of toluene. 50 mL of liquid strong stirring and left for one hour. We let the mixture return to room temperature and then we separate the components by column chromatography with hexane/ethyl acetate (5:1). Some of the products were mixtures and were differentiated via 1H-NMR.

Improved synthesis for Impracticatechol: 0.02 mol of 13, 0.04 mol of trinitromethyl sodium (6.92 g), 6 mmol of hydrazine hydrochloride (0.41 g), 4 mmol of hydroquinol (0.44 g), 10 mL of toluene and one rock (autoclaved for 3h) are added to a three-neck flask. The rest of the procedure is identical with the one above.


We have created an abomination and we do not regret it. We  developed a procedure for the creation of pentavalent carbon  centers with the help of substituted heptaazacubanes made by in situ assembly. Jonathan ate the manuscript of the supplementary data so  it is now unavailable. 

About the Authors  

Frederick Washing and Ben Dover have recently graduated and are  currently trying to find a job. Jonathan Mhama randomly came into  the building so now he is part of the lab staff. 

Author Contributions 

Frederick Washing made all of the illustrations and planned the  synthesis procedures with Ben Dover. All of the experiments and  purification procedures were performed by Ben Dover. Jonathan  Mhama helped with obtaining the compounds and left empty milk  cartons in the fridge. 

Conflicts of Interest 

We apologise for violating the chemistry laws. 

Notes and references 

  1. M. Mould, H. Ether, B. Urethra, A Partial Total Syntheis of  Impracticatechol, 2021, J. Immat. Sci, 1, 6.  
  2. A.M.Elfadly, I.F. Zeid, F.Z. Yehia, M.M. Abouelela, A.M. Rabie,  Production of aromatic hydrocarbons from catalytic pyrolysis of lignin  over acid-activated bentonite clay, Fuel Processing Technology Vol. 163,  2017

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