I would like to synthesize a di-N-substituted imidazole (compound 4) in its free base form or reduce it to generate an imidazoline (compound 5) to remove the bromide counterion to the imidazole ring. Imidazole to imidazoline reduction

I have tried the steps below resulting in the outcomes described below. Does anyone have any alternative suggestions on how to get compound 5 or somehow remove the bromide ion in compound 4? Thanks very much! Tested imidazole reduction steps

  • $\begingroup$ Could try NaBH4 in DMF or NaHB(OAc)3 in AcOH as described in this paper sciencedirect.com/science/article/abs/pii/S0040402017310906 but this does not look straightforward $\endgroup$
    – Waylander
    Nov 1, 2023 at 18:06
  • $\begingroup$ I found someone's thesis showing that they were able to add a sulfur at position 2 of di-N-substituted imidazoles. Would I be able to replace the alkyl i have on my position 2 with a sulfur using the reaction scheme they describe in Figure 35 page 40? Just trying to see if I can somehow salvage all the excess compound 4 I made and turn it into something marginally useful for my experiments jyx.jyu.fi/bitstream/handle/123456789/86607/1/… $\endgroup$
    – toodles
    Nov 2, 2023 at 0:18
  • $\begingroup$ You could try but I would not be optimisitic about it. $\endgroup$
    – Waylander
    Nov 2, 2023 at 7:46
  • $\begingroup$ Did you consider an anion exchange (the soft $\ce{Br^-}$ is substituted by say tetra fluoroborate $\ce{BF^-_4}$) subsequently followed by an electrochemical (i.e., regarding the potential adjustable) reduction? Do you have the relevant data at hand, i.e. a CV? For the former, see e.g. 2012Molecules4007, for the later see e.g., 2018JChemEduc197; both sources are open access. The scale could match well the Baran/Ika stirrer setup (see his lab page). $\endgroup$
    – Buttonwood
    Nov 2, 2023 at 15:47
  • $\begingroup$ Continuation: The company's advertising web site, a promotional video (small scale chemistry, this time without connecting Baran's Tesla to the reaction ...); Baran's talk Your Chemistry has Potential at ACS 2017 fall meeting, and a more recent tutorial like Simplifying synthesis with Electricity of the Kharkiv Chemical Seminar just in September, 2023. $\endgroup$
    – Buttonwood
    Nov 2, 2023 at 16:06

1 Answer 1


As Ref.1 pointed out, aromatic nitrogen heterocycles in which the nitrogen contributes only one electron to the $\pi$-system are electrophilic as compared to benzene, and show a reduction by lithium aluminum hydride, an active reducing agent. Thus, nitrogen heterocycles are more electrophilic than benzene and are susceptible to attack by the hydride ion from a complex metal hydride anion (e.g., $\ce{NaBH4}$). However, in protic solvents, the intermediate cyclic enamines can undergo further reduction such as heterocyclic ring opening. For example, when $\ce{NaBH4}$ (1n $1:5$ excess) was used in refluxing 95% ethanol as the solvent to reduce heterocyclic quaternary salts such as OP's imidazolinium ion $(\bf{4})$, the intermediate cyclic enamine (in OP's case, it is $\bf{5}$) can further undergoes reduction to give ring opening product, a diamine within one hour (Ref.2). It is also possible to quickly generate various functionalized heterocycles including macrocyclic ones in addition to these highly substituted diamino derivatives.

Nonetheless, Shvydenko, et al. (2017) have published their result that described a way to reduce imidazolium salts without ring opening (Ref.3):

enter image description here

Keep in mind that this reference was first mentioned here by Waylander in his comment to the question (many thanks). However, the authors have reported that all products having structure $\bf{5}$ (similar to OP's expected product) is unstable, specifically in even slight acetic condition (e.g., in NMR samples in $\ce{CDCl3}$). Bigger the fused ring, more the instability. This means open chain compounds without a fused ring such as OP's might be less stable, yet we don't know that for sure. Thus, it is tricky to use these conditions, but it is worth trying it to see the outcome.


  1. Robert E. Lyle and Paul S. Anderson, "The Reduction of Nitrogen Heterocycles with Complex Metal Hydrides," Advances in Heterocyclic Chemistry 1966, 6, Pages 45-93 (DOI: https://doi.org/10.1016/S0065-2725(08)60575-9).
  2. Erik F. Godefroi, "Reductive ring cleavage of 1,3-disubstituted imidazolium iodides by sodium borohydride," J. Org. Chem. 1968, 33(2), 860-862 (DOI: https://doi.org/10.1021/jo01266a089).
  3. Tetiana Shvydenko, Kostiantyn Nazarenko, Kostiantyn Shvydenko, Sergey Boron, Oleksii Gutov, Andrey Tolmachev, Aleksandr Kostyuk, "Reduction of imidazolium salts – An approach to diazocines and diazocanes," Tetrahedron 2017, 73(49), 6942-6953 (DOI: https://doi.org/10.1016/j.tet.2017.10.053).

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