Treatment of Substandard Rocket Fuel 1,1-Dimethylhydrazine Via Its Methylene Derivative into Heterocycles Based on Pyrrolo-[3,4c]Quinolines, Cyclododeca[b]piran and Pyrrole

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Sep 9

PMID 37685883

Authors

Elizaveta Ivanova

Maxim Maryasov

Vera Andreeva

Margarita Osipova

Tatyana Vasilieva

Alexey Eremkin

Olga Lodochnikova

Denis Grishaev

Oleg E Nasakin

Affiliations

Soon will be listed here.

Abstract

1,1-Dimethylhydrazine (Heptil, rocket fuel (UDMH)) is characterized by extremely high toxicity, teratogenicity and the ability to constantly absorb water from the atmosphere, losing its energy characteristics. In this regard, as well as due to the alternative fuel ("Angara") transition, there is a need for UDMH utilization in huge amounts. A more benign approach involves its immediate reaction with a formalin solution to form 1,1-dimethyl-2-methylene hydrazone (MDH), which is significantly less toxic by an order of magnitude. MDH can then be polymerized under acidic conditions, and the resulting product can be burned, yielding a substantial amount of nitrogen oxides. We propose an alternative to incineration by involving MDH in organic synthesis. We studied the reactions of MDH and its analog N,N-dimethyl-2-(methylenamino)ethane-1-amine (MDEA) with available CH-acids: tetracyanoethylated ketones (TCEKs) based on cyclohexanone, 4-propylcyclohexanone, 2-methylcyclohexanone, cyclododecanone and tetracyanoethane. The structures synthesized were confirmed by IR, H, C NMR and mass spectroscopy methods. MDH-based adducts were also identified by X-ray structural analysis. TCEKs and MDH, as well as TCEK based on cyclohexanone and MDEA, form bi- and tricyclic structures: pyrrolo [3,4c]-quinolines (using TCEKs based on cyclohexanone and 4-propylcyclohexanone), epiminomethanoquinoline-3,4-dicarbonitrile (using TCEK based on 2-methylcyclohexanone) and cyclododec[b]pyran-3,4-dicarbonitrile (using TCEK based on cyclododecanone). MDH and TCNEH formed a pyrrole derivative. Thus, we synthesized the structures that are of interest for molecular design and pharmaceutical chemistry.

References

Tompson D, Vearer D . Steady-state pharmacokinetic properties of a 24-hour prolonged-release formulation of ropinirole: results of two randomized studies in patients with Parkinson's disease. Clin Ther. 2008; 29(12):2654-66. DOI: 10.1016/j.clinthera.2007.12.010. View

Takacs D, Egyed O, Drahos L, Szabo P, Jemnitz K, Szabo M . Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect. Bioorg Med Chem. 2013; 21(13):3760-79. DOI: 10.1016/j.bmc.2013.04.034. View

Dressler D . [Apomorphine in the treatment of Parkinson's Disease]. Nervenarzt. 2004; 76(6):681-9. DOI: 10.1007/s00115-004-1830-4. View

Butora G, Morriello G, Kothandaraman S, Guiadeen D, Pasternak A, Parsons W . 4-Amino-2-alkyl-butyramides as small molecule CCR2 antagonists with favorable pharmacokinetic properties. Bioorg Med Chem Lett. 2006; 16(18):4715-22. DOI: 10.1016/j.bmcl.2006.07.011. View

Schmuck K, Ullmer C, Kalkman H, Probst A, Lubbert H . Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache?. Eur J Neurosci. 1996; 8(5):959-67. DOI: 10.1111/j.1460-9568.1996.tb01583.x. View

Allnoch L, Peters M, Wiemer F, Wohlsein P . Persistent Bilateral Mydriasis Associated With a Pituitary Adenoma in a Horse. J Equine Vet Sci. 2020; 85:102872. DOI: 10.1016/j.jevs.2019.102872. View

Shih S, Chen S, Hakimelahi G, Liu H, Tseng C, Shia K . Selective human enterovirus and rhinovirus inhibitors: An overview of capsid-binding and protease-inhibiting molecules. Med Res Rev. 2004; 24(4):449-74. PMC: 7168432. DOI: 10.1002/med.10067. View

Millan M, Maiofiss L, Cussac D, Audinot V, Boutin J, Newman-Tancredi A . Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002; 303(2):791-804. DOI: 10.1124/jpet.102.039867. View

Sheldrick G . SHELXT - integrated space-group and crystal-structure determination. Acta Crystallogr A Found Adv. 2014; 71(Pt 1):3-8. PMC: 4283466. DOI: 10.1107/S2053273314026370. View

10.

Micheli F, Pasquarello A, Tedesco G, Hamprecht D, Bonanomi G, Checchia A . Diaryl substituted pyrrolidinones and pyrrolones as 5-HT2C inhibitors: synthesis and biological evaluation. Bioorg Med Chem Lett. 2006; 16(15):3906-12. DOI: 10.1016/j.bmcl.2006.05.034. View

11.

Luo S, Li P, Li S, Du Z, Hu X, Fu Y . N,N-Dimethyl Tertiary Amino Group Mediated Dual Pancreas- and Lung-Targeting Therapy against Acute Pancreatitis. Mol Pharm. 2017; 14(5):1771-1781. DOI: 10.1021/acs.molpharmaceut.7b00028. View

12.

Fardis M, Jin H, Jabri S, Cai R, Mish M, Tsiang M . Effect of substitution on novel tricyclic HIV-1 integrase inhibitors. Bioorg Med Chem Lett. 2006; 16(15):4031-5. DOI: 10.1016/j.bmcl.2006.05.008. View

13.

Tatum R, McGowan C, Ireland J . Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review. Vet J. 2020; 266:105562. DOI: 10.1016/j.tvjl.2020.105562. View

14.

Sheldrick G . A short history of SHELX. Acta Crystallogr A. 2007; 64(Pt 1):112-22. DOI: 10.1107/S0108767307043930. View

15.

Banert K, Pester T . Too Short-Lived or Not Existing Species: N-Azidoamines Reinvestigated. J Org Chem. 2019; 84(7):4033-4039. DOI: 10.1021/acs.joc.9b00034. View