Synthesis of Hydrazones of Strained Polycyclic Hydrocarbons, Promising Building Blocks in Organic Chemistry ^†

Abstract

For the first time, the synthesis of unsubstituted hydrazones based on various strained polycyclic hydrocarbons, namely exo-exo-4-exo-acetoxypentacyclo[8.2.1.1^5,8.0^2,9.0^3,7]tetradecane, endo-endo-4-exo-acetoxypentacyclo[8.2.1.1^5,8.0^2,9.0^3,7]tetradecane and acetoxyhexacyclo[9.2.1.0^2,7.0^3,5.0^4,8.0^9,13]tetradecane, was carried out in four stages with high yields and selectivity.

1. Introduction

Hydrazones are a large class of organic compounds, and due to their high reactivity, they can act as intermediates in organic synthesis [1] or be used as independent substances in the various fields of science and technology [2]. Despite significant research in the field of hydrazone chemistry, we have noted that there is no information on the synthesis of hydrazones of various strained polycyclic hydrocarbons in the literature.

In this work, we have synthesized, for the first time, unsubstituted hydrazones based on various strained polycyclic hydrocarbons, which are of interest as promising building blocks in organic chemistry and medicine [3]. Polycyclic hydrocarbons are the result of the dimerization of norbornadiene with a wide range of unsaturated compounds under Diels-Alder reaction conditions [4,5,6,7]. Norbornadiene dimers are numerous, so we have chosen three compounds as the model objects of the study as they are the most frequently formed with good yields under dimerization reaction conditions, namely exo-exo-4-exo-acetoxypentacyclo[8.2.1.1^5,8.0^2,9.0^3,7] tetradecane, endo-endo-4-exo-acetoxypentacyclo[8.2.1.1^5,8.0^2,9.0^3,7] tetradecane and acetoxyhexacyclo[9.2.1.0^2,7.0^3,5.0^4,8.0^9,13] tetradecane.

2. Results and Discussion

The synthesis of hydrazones 1d–3d includes several successive stages, according to which, at the first stage, acetates 1a–3a are formed upon boiling the initial polycyclic hydrocarbons in acetic acid, where the three-carbon cycles of hydrogenated exo-exo, endo-endo-hexa- and the heptacyclic dimers of norbornadiene undergo acetoxylation [8]. The second stage involves the saponification of esters to the corresponding alcohols 1b–3b under the action of an alcoholic solution of potassium hydroxide [9]. The third and fourth stages involve the subsequent oxidation of alcohols to ketones 1c–3c and the introduction of a new functional group using an excess of hydrazine hydrate. In the first three stages, the yield of the final products was 85–90%. As a result, the corresponding unsubstituted hydrazones 1d–3d were obtained from strained polycyclic hydrocarbons in quantitative yield (Scheme 1).

Table 1. Structural formulas of hydrocarbons.

№	Hydrocarbons	R	R-OAc	R-OH	R=O	R=N-NH2
1			1a (90)	1b (90)	1c (90)	1d (~100)
2			2a (90)	2b (90)	2c (85)	2d (~100)
3			3a (90)	3b (90)	3c (89)	3d (~100)

shows all the structural formulas of strained polycyclic hydrocarbons, with the yields indicated in parentheses.

The spectral characteristics and synthesis of compounds 1a, 1b, 2a, 2b, 3a–3c are identical to the literature data [10,11].

3. Materials and Methods

The ¹H and ¹³C NMR spectra were procured on a Bruker Avance-500 spectrometer at 500.17 and 125.78 MHz, respectively. A mixture of CDCl₃ was used as a solvent. The chemical shifts are reported as δ values in parts per million relative to the internal standard Me₄Si. The coupling constants (J) are reported in Hertz.

3.1. General Procedure for the Synthesis of Hydrazones 1d–3d

A total of 50% of hydrazine hydrate (2.5 g, 0.05 mol) and triethylamine (20.2 g, 0.2 mol) were added to a solution of ketones 1d–3d (1 g) in isopropyl alcohol. The mixture was stirred and heated for 5 h. After cooling to room temperature, the mixture was concentrated under vacuum, diethyl ether (3 × 20 mL) was added to the reaction mass in portions, and the organic phase was separated and concentrated under vacuum, obtaining the corresponding hydrazone 1d–3d in the form of light yellow pastes. The yield is quantitative.

3.2. exo-exo-4-exo-Ketopentacyclo[8.2.1.1^5,8.0^2,9.0^3,7]tetradecane 1c

White solid. ¹H NMR (500 MHz, CDCl₃): δ (ppm) = 0.93 (d, J = 12 Hz, 1H), 1.04–1.08 (m, 2H), 1.36–1.37 (m, 3H), 1.53 (d, J = 10 Hz, 1H), 1.72–1.75 (m, 3H), 1.88–1.89 (m, 2H), 1.91–1.92 (m, 1H), 1.97–1.99 (m, 2H), 2.07 (s, 1H), 2.10 (s, 1H), 2.22–2.26 (m, 2H), 2.35 (s, 1H), 2.87 (s, 1H). ¹³C NMR (125 MHz, CDCl₃): δ (ppm) = 220.72, 58.56, 57.72, 52.69, 47.61, 46.51, 43.06, 41.98, 41.84, 35.73, 34.90, 34.86, 29.23, 28.69.

3.3. exo-exo-4-exo-Hydrazone-pentacyclo[8.2.1.1^5,8.0^2,9.0^3,7]tetradecane 1d

Light yellow pastes. ¹H NMR (500 MHz, CDCl₃): δ (ppm) = 0.80 (d, J = 12 Hz, 1H), 0.90–0.96 (m, 2H), 1.29–1.32 (m, 3H), 1.44 (d, J = 10 Hz, 1H), 1.74–1.76 (m, 3H), 1.85–1.86 (m, 2H), 1.98–2.01 (m, 1H), 2.26–2.27 (m, 2H), 2.33 (s, 1H), 2.37–2.38 (m, 2H), 2.57 (s, 1H), 2.79 (s, 1H), 4.69 (s, br, NH₂). ¹³C NMR (125 MHz, CDCl₃): δ (ppm) = 166.27, 57.81, 55.67, 53.22, 49.80, 46.91, 43.89, 41.97, 41.33, 38.42, 37.37, 34.97, 29.30, 28.65.

3.4. endo-endo-4-exo-Ketopentacyclo[8.2.1.1^5,8.0^2,9.0^3,7]tetradecane 2c

White solid. ¹H NMR (500 MHz, CDCl₃): δ (ppm) = 1.00 (d, J = 10 Hz, 1H), 1.27–1.33 (m, 3H), 1.38–1.43 (m, 4H), 1.73 (d, J = 5 Hz, 2H), 1.82–1.85 (m, 1H), 1.89–1.98 (m, 2H), 1.97–1.99 (m, 1H), 2.00–2.04 (m, 1H), 2.06 (s, 1H), 2.21 (s, 1H), 2.29–2.31 (m, 1H). ¹³C NMR (125 MHz, CDCl₃): δ (ppm) = 222.24, 54.88, 54.59, 52.87, 49.71, 49.08, 46.63, 42.08, 41.78, 38.60, 36.43, 35.88, 24.18, 24.01.

3.5. endo-endo-4-exo-Hydrazone-pentacyclo[8.2.1.1^5,8.0^2,9.0^3,7]tetradecane 2d

Light yellow pastes. ¹H NMR (500 MHz, CDCl₃): δ (ppm) = 0.95 (d, J = 10 Hz, 1H), 1.49–1.51 (m, 3H), 1.62–1.66 (m, 4H), 1.76 (d, J = 5 Hz, 2H), 1.84–1.87 (m, 1H), 1.90–1.97 (m, 2H), 2.03 (s, 1H), 2.25–2.29 (m, 4H), 2.34 (s, 1H), 2.49 (s, 1H), 3.11 (s, 1H), 3.60–3.63 (m, 1H), 4.30 (s, br, NH₂). ¹³C NMR (125 MHz, CDCl₃): δ (ppm) = 165.24, 54.20, 53.74, 50.95, 50.36, 43.04, 42.61, 42.60, 41.41, 41.20, 38.82, 37.22, 24.65, 24.64.

3.6. Hexacyclo[9.2.1.0^2,7.0^3,5.0^4,8.0^9,13]tetradecanyl Hydrazone 3d

Light yellow pastes. ¹H NMR (500 MHz, CDCl₃): δ (ppm) = 0.94–0.97 (m, 1H), 1.14–1.29 (m, 8H), 1.31–1.42 (m, 1H), 1.43–1.48 (m, 2H), 1.70 (s, 1H), 1.86–1.90 (m, 1H), 1.96 (s, 2H), 2.00–2.11 (m, 2H), 2.20 (s, 1H), 3.30–3.33 (m, 2H), 4.14–4.19 (m, 2H), 4.79 (s, br, NH₂). ¹³C NMR (125 MHz, CDCl₃): δ (ppm) =166.76, 44.96, 43.07, 41.92, 41.42, 40.08, 35.58, 34.47, 33.61, 32.20, 30.21, 14.99, 14.80, 14.08.

4. Conclusions

Thus, we have, for the first time, carried out the synthesis of previously unknown unsubstituted hydrazones of strained polycyclic hydrocarbons 1d–3d. It has been established that the presence of a double bond at the carbon atoms C12–C13 in the initial polycyclic hydrocarbons 1 and 2 leads to their resinification in the successive stages of the introduction of functional groups; therefore, their hydrogenated forms were used. Additionally, under the reaction conditions we had chosen, only one three-carbon cycle for polycyclic hydrocarbon 3 underwent acetoxylation.