: 88-97
Lviv Polytechnic National University
Lviv Polytechnic National University
Lviv Polytechnic National University
Lviv Polytechnic National University
Lviv Polytechnic National University

The nucleophilicity of the amino group in the 6-th and 7-th positions of 1,4-naphthoquinone and the comparison with the activity of the amino group in the 2-nd position of 1,4-naphthoquinone have been investigated. Therefore, alkylation reactions were performed with alkyl iodides, acylation with acetate anhydride, and also interaction with sulfinyl chloride and sulfonyl chloride was carried out.

Using EtI or i-PrI in benzene, with the addition of Et3N alkylation of 2,3,6-trichloro-7-amino-1,4-naphthoquinone, 2-amino-3,6-dichloro-7-nitro-1,4-naphthoquinone and 2-N-morpholino-3-chloro-6-amino-7-nitro-1,4-naphthoquinone was carried out.

2-N-acyl derivatives acylation of the amino group of 7-amino-2,3,6-trichloro-1,4-naphthoquinone, 2-amino-3,6-dichloro-1,4-naphthoquinone, 2-N-morpholino-3-chloro-6-amino-7-nitro-1,4-naphthoquinone was carried out with acetic anhydride at room temperature. Synthesis of 1,4-naphthoquinones with sulphonylamides and sulfonylamides was carried out in a medium of benzene, with addition of Et3N to give 2-N-sulfinyl (sulfonyl) amide derivatives, 6-N-sulfinyl (sulfonyl) amide derivatives and 7-N-sulfinyl (sulfonyl) amide derivative. Alkylation of diamines: 2,7-diamino-3,6-dichloro-1,4-naphthoquinone and 2-N-morpholino-3-chloro-6,7-diamino-1,4-naphthoquinone, yielded 2,7-dialkyl derivatives, which indicates a lower reactivity of amino groups than in the 6.7-dialkyl derivatives.

Products of diacylation are formed by the way of acylating diamines 2,7-diamino-2,6-dichloro-1,4-naphthoquinone and 2-N-morpholino-3-chloro-6,7-diamino-1,4-naphthoquinone

         As a result of our research, we have seen that under the same conditions of reaction, the position of the amino group has a significant influence on the yield of the final product. In the presence of an amino group in the molecule of substituted 1,4-naphthoquinone there is displacement of electronic density in the direction of the naphthoquinone cycle with an appropriate change of charge on the carbon atoms in a certain position. 7-Amino substituted derivatives give yields greater than 75%, 6-amino substituted - 60-70%, and 2-amino-substituted compounds - 40-50% respectively.

It was established that due to the displacement of the electron density from the amino group in the 2-nd position towards the quinone cycle, it exhibits very weak nucleophilic properties.

For synthesized substances, a virtual biological screening was conducted using the PASS online program, which demonstrated the feasibility of further studies of the biological activity of 2,6,7-substituted 1,4-naphthoquinones to find new drugs with high pharmacological effects and low toxicity.

1. F. Giroud, R. Milton, B. Tan, et al. Simplifying Enzymatic Biofuel Cells: Immobilized
Naphthoquinone as a Biocathodic Orientational Moiety and Bioanodic Electron Mediator // ACS Catal. –
2015, 5, P. 1240–1244. 2. V. Tandon, D. Yadav, R. Singh, et al. Synthesis and biological evaluation of
novel (L)-α-amino acid methyl ester, heteroalkyl, and aryl substituted 1,4-naphthoquinone derivatives as
antifungal and antibacterial agents // Bioorg. Med. Chem. Letters – 2005. – No. 15. – P. 5324–5328.
3. S. Sandur, H. Ichikawa, G. Sethi et al. Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Suppresses
NF-B Activation and NF-kB-regulated Gene Products Through Modulation of p65 and IkBα Kinase
Activation, Leading to Potentiation of Apoptosis Induced by Cytokine and Chemotherapeutic Agents //
J. Biological Chemistry – 2006. – No. 25. – Vol. 281. – P. 17023–17033. 4. Fries K., Pense W., Peters O.
Uber lin Benzo-p-thiazino-chinone // Ber. – 1928. – No. 61. – P. 1395–1401. 5. Бучкевич І. Р., Платонов
М. О., Стасевич М. В., Лубенець В. І., Мусянович Р. Я. Синтез нових азотовмісних похідних 2,3,6-
трихлор-1,4-нафтохінону // Вісник Національного університету „Львівська політехніка” Хімія,
технологія речовин та їх застосування. – 2009. – № 644. – С. 111–114. 6. Шишкина Р. П., Маматюк
В. П., Фокин Е. И. Сульфирование и сульфохлорирование 2,3-дихлор-1,4-нафтохинона. // Изв. Сиб.
Отд. АН СССР. Сер. Химия. – 1984. – № 3. – C. 855–857. 7. Pingaew R., Prachayasittikul V.,
Worachartcheewan A. et al. Novel 1,4-naphthoquinone-based sulfonamides: synthesis, QSAR, anticancer
and antimalarial studies / Euro. J.Med. Chem. – 2015. – No. 103. – P. 446–459. 8. Buchkevych I.,
Stasevych M., Musyanovych R. et al. S- and N,S-Containing heterocycles based on sulfenyl chlorides of
substituted 1,4-naphthoquinone // Chemistry of Heterocyclic Compounds. – 2010. – Vol. 46(4). –
P. 502–504. 9. Satheshkumar A., Elango K. Spectroscopic and theoretical studies on the nucleophilic
substitution of 2,3-dichloronaphthoquinone with para-substituted anilines in solid state via initial charge
transfer complexation // Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. –
2012. – Vol. 98. – P. 378–383. 10. Ластухін Ю. О., Воронов С. А. Органічна хімія. – Львів: Центр
Європи, 2001. – 864 с. 11. Bolibrukh K., Polovkovych S., Khoumeri O. et al. Synthesis and anti-platelet
activity of thiosulfonate derivatives containing a quinone moiety // Scientia Pharmaceutica. – 2015. –
Vol. 83 (2). – P. 221–231. 12. PASS (Prediction of Activity Spectra for Substances) [електронний ресурс] /
режим доступу до ресурсу: Online/.