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Proceeding Paper

A New Synthesis of Polyheterocyclic Compounds Containing Nitrogen and Boron Atoms †

by
Victor Yu Kirsanov
and
Elena B. Rakhimova
*
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, 450075 Ufa, Russia
*
Author to whom correspondence should be addressed.
Presented at the 27th International Electronic Conference on Synthetic Organic Chemistry (ECSOC-27), 15–30 November 2023; Available online: https://ecsoc-27.sciforum.net/.
Chem. Proc. 2023, 14(1), 31; https://doi.org/10.3390/ecsoc-27-16103
Published: 15 November 2023

Abstract

:
Tetraazatricyclanes containing two boron atoms in the molecular framework were synthesized for the first time via the heterocyclization reaction of tetraamines with tetrakis(dimethylamino)diborane. Tetrakis(dimethylamino)diborane is a new starting reagent in the synthesis of polyheterocyclic compounds that may be of interest as cytotoxic agents.

1. Introduction

Organic nitrogen compounds occupy a special place among synthetic substances. The number of new heterocyclic compounds containing nitrogen atoms and possessing pharmacological properties [1] is constantly growing. Earlier, refs. [2,3] it was shown that the condensation of triethylenetetramine 1 with glyoxal under optimal conditions (H2O, 5 °C) in the presence of Ca(OH)2 (Scheme 1) leads to the preparation of different tetraazatricyclanes, namely cis/trans-octahydrotetraazanaphthalenes 2, 3 and cis/trans-decahydrodiimidazopyrazines 4, 5. Replacing the solvent and increasing the reaction temperature affect the ratio and yield of the resulting tricyclanes [4,5,6]. N,N′-bis(aminoethyl)propane-1,3-diamine 6 can be used as another linear tetramine [7]. As a result, the condensation of tetramine 6 with glyoxal (EtOH, 0 °C) allows one to obtain tetraazatricyclane 7. Non-trivial framework bis-aminals 8 were synthesized using the electrophilic agent cyclohexane-1,2-dione [8] (Scheme 1).
The inclusion of boron in the molecular framework of azapolycycles is of undoubted interest. Tetraamino-substituted diborane compounds are important in diborane chemistry. It is worth highlighting the tetrakis(dimethylamino)diborane B2(NMe2)4 9, which is used as the synthetic precursor to most other derivatives. It has been demonstrated [9,10] that that reaction of B2(NMe2)4 with 1,2-diamines yields different products 1012 depending on the diamine employed (Scheme 2).
As far as we know, there are no data about the involvement of polyamines in the heterocyclization reaction with (dimethylamino)diborane in the scientific literature. In this regard, the goal of this work was to study the possibility of using (dimethylamino)diborane as a key reagent in the synthesis of tetraazatricyclanes containing boron atoms in the molecular framework.

2. Results and Discussion

With preliminary experiments, we established that the interaction of triethylenetetraamine 1 with tetrakis(dimethylamino)diborane 9 in a molar ratio of 1:1 under reaction conditions (EtOH, 0 °C, 2 h) leads to the selective formation of hexahydro-3H,6H-2a,5,6,8a-tetraaza-5a,8b-diboraacenaphthylene 13 in 35% yield, the molecule of which is a 6/5/6 tricyclic system (Scheme 3).
The application of other linear polyamines, namely 1,2-bis(3-aminopropylamino)ethane 14 and N,N′-bis(3-aminopropyl)-1,3-propanediamine 16, in such a reaction under the optimal conditions gave previously unknown analogous products—decahydro-2a,6,7,10a-tetraaza-6a,10b-diboracyclopenta[ef]heptalene 15 and decahydro-1H-3a,7,8,11a-tetraaza-7a,11b-diborabenzo[ef]heptalene 17, respectively, in 39–42% yields (Scheme 4).

3. Conclusions

Thus, in the present study we have demonstrated that the intermolecular heterocyclization of polyamines with tetrakis(dimethylamino)diborane provides for the synthesis of novel diboron-containing tetraazatricyclanes. The obtained compounds may be of interest as precursors in the further synthesis of functionally-substituted tetracyclanes, which have potential cytotoxic and antitumor activity [11,12,13].

4. Experimental Part

The 1H and 13C NMR spectra, including two-dimensional homo- (COSY) and heteronuclear (HSQC, HMBC) spectra, were recorded using a Bruker Avance 500 spectrometer (500.17 MHz for 1H and 125.78 MHz for 13C) according to standard Bruker protocols, using DMSO-d6 as solvent and TMS as internal standard. Commercially available reagents used in this work were purchased from Sigma–Aldrich (St. Louis, MO, USA) and Acros Organics (Geel, Belgium).
  • Heterocyclization of polyamines with tetrakis(dimethylamino)diborane (general procedure). A round-bottom flask mounted on a magnetic stirrer was charged with a solution of corresponding polyamine (2.00 mmol) in 5 mL of ethanol and was cooled in an ice bath at 0 °C, then tetrakis(dimethylamino)diborane (2.00 mmol) in 5 mL of ethanol was added. The mixture was stirred at 0 °C for 2 h and was left in the cold for 12 h. The resulting precipitate was filtered off. Pure compounds 13, 15, 17 were thus isolated as white powders.
  • Hexahydro-3H,6H-2a,5,6,8a-tetraaza-5a,8b-diboraacenaphthylene (13): Yield 35%. 1H NMR: δ 2.53–2.59 (m, 8H), 2.62–2.65 (m, 4H). 13C NMR spectrum: δ 41.0, 49.0, 51.1. 11B{1H} NMR: δ 1.40 (br. s).
  • Decahydro-2a,6,7,10a-tetraaza-6a,10b-diboracyclopenta[ef]heptalene (15): Yield 39%. 1H NMR: δ 2.43–2.47 (m, 4H), 2.54–2.59 (m, 8H), 2.64–2.69 (m, 4H). 13C NMR spectrum: δ 35.7, 46.5, 46.9, 50.2.
  • Decahydro-1H-3a,7,8,11a-tetraaza-7a,11b-diborabenzo[ef]heptalene (17): Yield 42%. 1H NMR: δ 2.15–2.19 (m, 2H), 2.47–2.51 (m, 4H), 2.57–2.63 (m, 8H), 2.66–2.69 (m, 4H). 13C NMR spectrum: δ 28.2, 32.4, 45.2, 45.7, 49.5.

Author Contributions

The authors (V.Y.K. and E.B.R.) have equally contributed to this work. All authors have read and agreed to the published version of the manuscript.

Funding

This study was carried out under the research plans of the IPC UFRC RAS, FMRS-2022-0079 (2022–2024) FMRS-2022-0074 (2022–2024).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in the article.

Acknowledgments

The structural studies of the synthesized compounds were performed with the use of Collective Usage Centre “Agidel” at the Institute of Petrochemistry and Catalysis of UFRC RAS.

Conflicts of Interest

The authors declare no conflict of interest.

References

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Scheme 1. Condensation of polyamines with dialdehyde [2,3,4,5,6,7] and diketone [8] in the synthesis of tetraazatricyclanes.
Scheme 1. Condensation of polyamines with dialdehyde [2,3,4,5,6,7] and diketone [8] in the synthesis of tetraazatricyclanes.
Chemproc 14 00031 sch001
Scheme 2. Reaction of 1,2-diamines [9,10] with tetrakis(dimethylamino)diborane.
Scheme 2. Reaction of 1,2-diamines [9,10] with tetrakis(dimethylamino)diborane.
Chemproc 14 00031 sch002
Scheme 3. Synthesis of perhydro tetraazadiboraacenaphthylene.
Scheme 3. Synthesis of perhydro tetraazadiboraacenaphthylene.
Chemproc 14 00031 sch003
Scheme 4. Heterocyclization of polyamines with tetrakis(dimethylamino)diborane.
Scheme 4. Heterocyclization of polyamines with tetrakis(dimethylamino)diborane.
Chemproc 14 00031 sch004
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MDPI and ACS Style

Kirsanov, V.Y.; Rakhimova, E.B. A New Synthesis of Polyheterocyclic Compounds Containing Nitrogen and Boron Atoms. Chem. Proc. 2023, 14, 31. https://doi.org/10.3390/ecsoc-27-16103

AMA Style

Kirsanov VY, Rakhimova EB. A New Synthesis of Polyheterocyclic Compounds Containing Nitrogen and Boron Atoms. Chemistry Proceedings. 2023; 14(1):31. https://doi.org/10.3390/ecsoc-27-16103

Chicago/Turabian Style

Kirsanov, Victor Yu, and Elena B. Rakhimova. 2023. "A New Synthesis of Polyheterocyclic Compounds Containing Nitrogen and Boron Atoms" Chemistry Proceedings 14, no. 1: 31. https://doi.org/10.3390/ecsoc-27-16103

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