Research in processes of the nitrogen-containing heterocycles obtaining from intermediate of the off-spec fuel disposal — 1,1-dimethyl-2-methylenehydrazone

Objectives. To introduce the intermediate obtained from the disposal of unusable rocket propellant—1,1-dimethyl2-methylenehydrazone (DMH)—into the synthesis of pyrroloquinolines (and pyridines) with potential applications in medicine; to carry out reactions of DMH with tetracyanoethylated ketones (TCEKs) derived from acetone, methyl ethyl ketone, cyclohexanone, 4-propylcyclohexanone, and 2-methylcyclohexanone; to investigate the prospects for increasing the yields of target products by performing the same syntheses under microwave irradiation (MWI) and using an ultrasonic reactor.

Methods. TCEKs were prepared from tetracyanoethylene (TCNE) and the corresponding ketone in dioxane, acetone, or ethanol, with the presence of concentrated hydrochloric or sulfuric acid as a catalyst. Pyrroloquinolines (and pyridines) were synthesized from DMH and the corresponding TCEK in ethyl acetate with base as a catalyst. Syntheses were carried out under standard conditions using a magnetic stirrer, an ultrasonic reactor (Vologda, Russia), and a UWave-2000 microwave reactor (Sineo Microwave Chemistry Technology Co., China). Reaction progress and product purity were monitored by thin-layer chromatography on Sorbfil plates (Sorbfil, Russia). The TCNE presence in the reaction mixture was determined by the hydroquinone test. Melting and decomposition points were measured using anOptiMeltMPA100 apparatus (OptiMelt, USA). Structural identification was performed by infrared spectroscopy (FSM-1202, SpektroLab, Russia), ¹H and ¹³C nuclear magnetic resonance spectroscopy in dimethyl sulfoxide d₆ on a Bruker AVANCE 400 WB spectrometer (Bruker Corporation, USA), and mass spectrometry using a quadrupole time-of-flight AB SCIEX TripleTOF 5600 spectrometer (AB SCIEX PTE. Ltd., Singapore) and a quadrupole gas chromatography–mass spectrometer GCMS-QP2020 NX (Shimadzu, Germany).

Results. Reliable procedures developed for the synthesis of pyrrolopyridines from acetone and methyl ethyl ketone without tar formation under ultrasonic stirring and MWI demonstrated significantly increased yields. The highest conversion of DMH to pyrroloquinoline was achieved from cyclohexanone, providing the target product in 92% yield within the shortest reaction time of 2 min under MWI conditions. However, for derivatives of 4-propylcyclohexanone and 2-methylcyclohexanone, the described synthesis modifications did not give the desired results: in the former case, a decrease in yield was observed as compared to standard methods, while in the latter, only a slight increase was obtained.

Conclusions. Ultrasonic stirring and MWI are effective for the conversion of DMH into pyrrolopyridines based on aliphatic TCEKs, but unsuitable for the synthesis of pyrroloquinolines derived from 4-propylcyclohexanone and 2-methylcyclohexanone. The high yield of pyrroloquinoline from cyclohexanone (92%) suggests potential for implementing the rapid MWI-promoted reaction between DMH and cyclohexanone-based TCEK in industrial production.

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