Aminomethylated Hydroxinaphthalenes: Synthesis and Application

Authors: Slitikov P.V., Evdokimenkova Yu.B. Published: 24.02.2021
Published in issue: #1(94)/2021  
DOI: 10.18698/1812-3368-2021-1-126-143

Category: Chemistry | Chapter: Organic Chemistry  
Keywords: Betti aminobenzylation, primary amines, secondary amines, formaldehyde, 2-naphthol, dihydroxynaphthalenes, Mannich aminomethylation

The analysis of the literature is carried out and the results of the synthetic approaches to the aminomethylation of hydroxy derivatives of naphthalenes developed over the past 20 years are presented. Most of the described aminomethylation processes proceed as Mannich aminomethylation or, as a special case of a similar condensation --- aminobenzylation according to Betti. The results of all studies are grouped according to the nature of the amine used in the synthesis: primary, secondary, tertiary. Most of the examples were considered for 2-naphthol, however, as the analysis of literature data shows, similar methods are applicable to 1-naphthol and dihydroxynaphthalenes with different positions of OH groups in the ring --- often only the yields of the target product differ. Both the classical methods for the preparation of Mannich and Betti bases using the carbonyl component (formaldehyde, benzaldehyde and its derivatives, respectively) and special cases of synthesis, in which condensation is carried out by means of halogen derivatives, substituted azacrown ethers, etc., are presented. Particular attention is paid to the use of various catalysts and activators, allowing to significantly simplify the synthetic procedures and increase the yields of target compounds. The main fields of application of aminomethylated derivatives of hydroxynaphthalenes are presented


[1] Mannich C., Krosche W. Ueber ein Kondensationsprodukt aus Formaldehyd, Ammoniak und Antipyrin. Arch. Pharm., 1912, art. 250, nо. 1, pp. 647--667. DOI: https://doi.org/10.1002/ardp.19122500151

[2] Betti M. β-Naphthol phenilaminomethane. Org. Syntheses, 1929, vol. 9, pp. 60. DOI: https://doi.org/10.1002/0471264180.os009.21

[3] Sharghi H., Khalifeh R., Salimi Beni A.R. Synthesis of new lariat ethers containing polycyclic phenols and heterocyclic aromatic compound on graphite surface via Mannich reaction. J. Iran. Chem. Soc., 2010, vol. 7, nо. 1, pp. 275--288. DOI: https://doi.org/10.1007/BF03245889

[4] Mojtahedi M.M., Sharifi A., Mohsenzadeh F., et al. Microwave-assisted aminomethylation of electron-rich compounds under solvent-free condition. Synth. Commun., 2000, vol. 30, iss. 1, pp. 69--72. DOI: https://doi.org/10.1080/00397910008087294

[5] Rogovsky V.S., Arzamasova T.M., Rosenfel’d M.A., et al. Effect of an inclusion complex of an aminomethylated dihydroquercetin derivative in cyclodextrin on ozone-induced oxidation of fibrinogen. Pharm. Chem. J., 2013, vol. 47, no 6, pp. 295--295. DOI: https://doi.org/10.1007/s11094-013-0946-x

[6] Shi Y., Wang O., Gao S. Recent advances in the intromolecular Mannich reaction in nature products total synthesis. Org. Chem. Front., 2018, vol. 5, iss. 6, pp. 1049--1066. DOI: https://doi.org/10.1039/C7QO01079F

[7] Lukashenko A.V., Osipov D.V., Osyanin V.A., et al. The reaction of 1,2-naphthoquinone 1-methides with syncarpic acid. Chem. Heterocycl. Comp., 2019, vol. 55, no. 10, pp. 1004--1006. DOI: https://doi.org/10.1007/s10593-019-02569-4

[8] Korzhenko К.S., Osipov D.V., Osyanin V.A., et al. Reaction of cross-conjugated push-pull enamino ketones with 1,2-naphthoquinone 1-methides: synthesis of 3-aryl-1-(1H-benzo[f]chromen-2-yl)prop-2-en-1-ones. Chem. Heterocyc. Comp., 2018, vol. 54, no 10, pp. 940--945. DOI: https://doi.org/10.1007/s10593-018-2377-9

[9] Lukashenko A.V., Osyanin V.A., Osipov D.V., et al. Reaction of push-pull enaminoketones and in situ generated orthoquinone methides: synthesis of 3-acyl-4H-chromenes and 2-acyl-1H-benzo[f]chromenes as precursors for hydroxybenzylated heterocycles. J. Org. Chem., 2017, vol. 82, iss. 3, pp. 1517--1528. DOI: https://doi.org/10.1021/acs.joc.6b02716

[10] Lukashenko A.V., Osipov D.V., Osyanin V.A., et al. Reactions of 1-[(dimethylamino)methyl]naphthalen-2-ols with cyclic push-pull nitroenamines. Chem. Heterocyc. Comp., 2017, vol. 53, no 12, pp. 1369--1372. DOI: https://doi.org/10.1007/s10593-018-2219-9

[11] Slitikov P.V., Rasadkina E.N. Phosphorylation of aminomethylated derivatives of 2,7-dihydroxynaphthalenes. Russ. J. Gen. Chem., 2016, vol. 86, no. 3, pp. 544--550. DOI: https://doi.org/10.1134/S1070363216030099

[12] Mrug G.P., Myshko N.V., Bondarenko S.P., et al. One-pot synthesis of B-ring ortho-hydroxylated sappanin-type homoisoflavonoids. J. Org. Chem., 2019, vol. 84, iss. 11, pp. 7138--7147. DOI: https://doi.org/10.1021/acs.joc.9b00814

[13] Osyanin V.A., Lukashenko A.V., Osipov D.V., et al. Synthesis of 2-nitro-1H-benzo[f]chromenes. Chem. Heterocyc. Comp., 2015, vol. 50, no. 11, pp. 1528--1533. DOI: https://doi.org/10.1007/s10593-014-1620-2

[14] Ded M.L., Pegu C.D., Deka B., et al. Bronsted-acid-mediated divergent reactions of Betti bases with indoles: an approach to chromeno[2,3-b]indoles through intramolecular dehydrogenative C2‐alkoxylation of indole. Eur. J. Org. Chem., 2016, vol. 2016, iss. 20, pp. 3441--3448. DOI: https://doi.org/10.1002/ejoc.201600546

[15] Spasov A.A., Badkov D.A., Osipov D.V., et al. Synthesis, in vitro and in vivo evaluation of 2-aryl-4H-chromene and 3-aryl-1H-benzo[f]chromene derivatives as novel α-glucosidase inhibitors. Bioorganic Med. Chem. Lett., 2019, vol. 29, iss. 1, pp. 119--123. DOI: https://doi.org/10.1016/j.bmcl.2018.10.018

[16] Spasov A.A., Badkov D.A., Prokhorova T.Yu., et al. Synthesis and biological evaluation of 2-acylbenzofuranes as novel α-glucosidase inhibitors with hypoglycemic activity. Chem. Biol. Drug Des., 2017, vol. 90, iss. 6, pp. 1184--1189. DOI: https://doi.org/10.1111/cbdd.13038

[17] Chen H.-L., Chang C.-Y., Lee H.-T., et al. Synthesis and pharmacological exploitation of clioquinol-derived copper-binding apoptosis inducers triggering reactive oxygen species generation and MAPK pathway activation. Bioorganic Med. Chem., 2009, vol. 17, iss. 20, pp. 7239--7247. DOI: https://doi.org/10.1016/j.bmc.2009.08.054

[18] Silvestri I., Lyu H., Fata F., et al. Ectopic suicide inhibition of thioredoxin glutathione reductase. Free Radic. Biol. Med., 2020, vol. 147, pp. 200--211. DOI: https://doi.org/10.1016/j.freeradbiomed.2019.12.019

[19] Vojacek S., Beese K., Alhalabi Z., et al. Three-component aminoalkylations yielding dihydronaphthoxazine-based sirtuin inhibitors: scaffold modification and exploration of space for polar side-chains. Arch. Pharm., 2017, vol. 350, iss. 7, special issue: Carl Mannich, art. e1700097. DOI: https://doi.org/10.1002/ardp.201700097

[20] Lei X., Chelamalla N. Dioxomolybdenum(VI) complexes with linear and tripodal tetradenate ligands: synthesis, structures and their use as olefin epoxidation catalysts. Polyhedron, 2013, vol. 49, iss. 1, pp. 244--251. DOI: https://doi.org/10.1016/j.poly.2012.10.022

[21] Jedrzkiewicz D., Ejfler J., Gulia N., et al. Designing ancillary ligands for heteroleptic/homoleptic zinc complex formation: synthesis, structures and application in ROP of lactides. Dalton Trans., 2015, vol. 44, iss. 30, pp. 13700--13715. DOI: https://doi.org/10.1039/C5DT01553G

[22] Kuznik N., Wyskoska M., Jarosz M., et al. Aminophenol complexes of Fe(III) as promising T1 accelerators. Arab. J. Chem., 2019, vol. 12, iss. 7, pp. 1424--1435. DOI: https://doi.org/10.1016/j.arabjc.2014.11.009

[23] Antonov L., Deneva V., Simeonov S., et al. Exploiting tautomerism for switching and signaling. Angew. Chem. Int. Ed., 2009, vol. 48, iss. 42, pp. 7875--7878.DOI: https://doi.org/10.1002/anie.200903301

[24] Tavlinova-Kirilova M., Marinova M., Angelova P., et al. Three component condensation of a Betti-type --- efficient tool for synthesis of chiral naphthoxazines and aminobenzylnaphthols for enantioselective diethylzinc addition to aldehydes. Bulgarian Chem. Commun., 2016, vol. 48, no. 4, pp. 705--712.

[25] Osipov D.V., Osyanin V.A., Khaysanova G.D., et al. An inverse electron demand azo-diels--alder reaction of o-quinone methides and imino ethers: synthesis of benzocondensed 1,3-oxazines. J. Org. Chem., 2018, vol. 83, iss. 8, pp. 4775--4785. DOI: https://doi.org/10.1021/acs.joc.8b00692

[26] Woodgate P.D., Horner G.M., Maynard N.P., et al. Synthesis of dioxazaborocines from N,N’-alkylbridged-bis(bis(2-hydroxybenzyl)aminomethyl)amines. J. Organomet. Chem., 2000, vol. 595, iss. 2, pp. 215--223. DOI: https://doi.org/10.1016/S0022-328X(99)00627-0

[27] Woodgate P.D., Horner G.M., Maynard N.P. A novel method for functionalising resorcinarenes. Tetrahedron Lett., 1999, vol. 40, iss. 35, pp. 6507--6510. DOI: doi.org/10.1016/S0040-4039(99)01338-6

[28] Woodgate P.D., Horner G.M., Maynard N.P., et al. Synthesis of dioxazaborocines from N-substituted-bis(2-hydroxyaryl)aminomethylamines. J. Organomet. Chem., 1999, vol. 592, iss. 2, pp. 180--193. DOI: https://doi.org/10.1016/S0022-328X(99)00510-0

[29] Lery F.-X., Kunesch N., George P., et al. A new general route to novel azomethine ylides for cycloaddition reactions. Heterocycles, 2002, vol. 57, no. 9, pp. 1599--1614. DOI: https://doi.org/10.3987/COM-02-9484

[30] Diaz-Oviedo C., Quevedo R. Role of hydrogen bonding in the selectivity of aromatic Mannich reaction of tyramines: macrocyclization vs. linear condensation. J. Mol. Structure, 2020, vol. 1202, art. 127283. DOI: https://doi.org/10.1016/j.molstruc.2019.127283

[31] Choi S., Park J. Naphthoxazine benzoxazine-based monomer, polymer thereof, electrode for fuel cell including the polymer, electrolyte membrane for fuel cell including the polymer, and fuel cell using the electrode. Patent US 2055706A1. Appl. 31.10.2008, publ. 06.05.2009.

[32] Choi S., Park J. Naphthoxazine benzoxazine-based monomer, polymer thereof, electrode for fuel cell including the polymer, electrolyte membrane for fuel cell including the polymer, and fuel cell using the electrode. Patent US 8188210B2. Appl. 29.05.2012, publ. 29.05.2012.

[33] Sharma S., Nath M. Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins. Beilstein J. Org. Chem., 2013, vol. 9, no. 3, pp. 496--502. DOI: https://doi.org/10.3762/bjoc.9.53

[34] Matsumoto J., Ishizu M., Kawano R., et al. Generation of quinone methide from aminomethyl(hydroxy)arenes precursors in aqueous solution. Tetrahedron, 2005, vol. 61, iss. 24, pp. 5735--5740. DOI: https://doi.org/10.1016/j.tet.2005.04.037

[35] Fujiwara M., Sakamoto M., Komeyama K., et al. Convenient synthesis of 2-amino-4H-chromenes from photochemically generated o-quinone methides and malononitrile. J. Heterocyclic Chem., 2015, vol. 52, iss. 1, pp. 59--66. DOI: https://doi.org/10.1002/jhet.1964

[36] Ganesan S.S., Rajendran N., Sundarakumar S.I., et al. β-Naphthol in glycerol: a versatile pair for efficient and convenient synthesis of aminonaphthols, naphtho-1,3-oxazines, and benzoxanthenes. Synthesis, 2013, vol. 45, no. 11, pp. 1564--1568. DOI: https://doi.org/10.1055/s-0033-1338430

[37] Arzephoni A.Y., Naimi-Jamal M.R., Sharifi A., et al. [Omim][BF4] ionic liquid, a green and recyclable medium for one-pot aminomethylation of electron-rich aromatic compounds. J. Chem. Res., 2013, vol. 37, iss. 4, pp. 216--218. DOI: https://doi.org/10.3184%2F174751913X13635476751996

[38] Abonia R., Castillo J., Insuasty B., et al. Efficient catalyst-free four-component synthesis of novel γ-aminoethers mediated by a Mannich type reaction. ACS Comb. Sci., 2013, vol. 15, iss. 1, pp. 2--9. DOI: https://doi.org/10.1021/co300105t

[39] Mohanty S., Suresh D., Balakrishna M.S., et al. Phosphine free diamino-diol based palladium catalysts and their application in Suzuki --- Miyaura cross-coupling reactions. J. Organomet. Chem., 2009, vol. 694, iss. 13, pp. 2114--2121. DOI: https://doi.org/10.1016/j.jorganchem.2009.02.019

[40] Gawdzik B., Wakdemar I. Synthesis, structure, and stereochemistry of the bora derivatives of 1-[(2-hydroxy-1-naphthyl)methyl]proline. Tetrahedron: Asym., 2005, vol. 16, iss. 11, pp. 2019--2023. DOI: https://doi.org/10.1016/j.tetasy.2005.04.021

[41] Nifant’ev E.E., Slitikov P.V., Rasadkina E.N. Aminomethylated derivatives of 2,7-dihydroxynaphthalene. Dokl. Chem., 2014, vol. 457, no. 1, pp. 129--131. DOI: https://doi.org/10.1134/S0012500814070052

[42] Nifant’ev E.E., Slitikov P.V., Rasadkina E.N. Bis(aminomethylation) of dihydroxynaphthalenes. Dokl. Chem., 2015, vol. 463, no. 1, pp. 178--180. DOI: https://doi.org/10.1134/S0012500815070046

[43] Slitikov P.V., Rasadkina E.N. Aminomethylated derivatives of 2,6-dihydroxynaphthalene and features of their phosphorylation. ХХ Mendeleev Cong. Gen. Appl. Chem. Ekaterinburg, 2016, vol. 1, p. 326.

[44] Slitikov P.V., Rasadkina E.N. Aminomethylation of naphthalen-2-ol and naphthalene-2,7-diol. Russ. J. Org. Chem., 2016, vol. 52, no. 10, pp. 1432--1435. DOI: https://doi.org/10.1134/S1070428016100109

[45] Huang P.-J.J., Cameron T.S., Jha A. Novel synthesis of 2,2-dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b]pyrans. Tetrahedron Lett., 2009, vol. 50, iss. 1, pp. 51--54. DOI: https://doi.org/10.1016/j.tetlet.2008.10.083

[46] Osipov D.V., Osyanin V.A., Klimochkin Yu.N. New synthesis of 3-amino-1H-benzo[f]chromene-2-carbonitriles. Russ. J. Org. Chem., 2013, vol. 49, no. 3, pp. 398--402. DOI: https://doi.org/10.1134/S1070428013030147

[47] Jha A., Nawal K.P., Trikha S., et al. Novel synthesis of 2-naphthol Mannich bases and their NMR behaviour. Can. J. Chem., 2006, vol. 84, no. 6, pp. 843--853. DOI: https://doi.org/10.1139/v06-081

[48] Ganesan S.S., Asaithampi G. Magnesium sulfate promoted efficient and green synthesis of aminoalkyl, amidoalkyl and diarylmethane derivatives. Asian J. Chem., 2014, vol. 26, no. 24, pp. 8380--8382. DOI: http://dx.doi.org/10.14233/ajchem.2014.17618

[49] Teimuri-Mofrad R., Gholamhosseini-Nazari M., Esmati S., et al. An efficient and green method for the synthesis of Betti base employing nano-SiO2-H3BO3 as a novel recyclable heterogeneous catalyst. Res. Chem. Intermed., 2017, vol. 43, no. 12, pp. 6845--6861. DOI: https://doi.org/10.1007/s11164-017-3024-2

[50] Sun W., Lin H., Zhou W., et al. Oxidative ortho-aminomethylation of phenols via C--H and C--C bond cleavage. RCS Advances, 2014, vol. 4, iss 15, pp. 7491--7494. DOI: https://doi.org/10.1039/C3RA46373G

[51] Gupta S., Chandna N., Dubey P., et al. GO-Cu7S4 catalyzed: ortho-aminomethylation of phenol derivatives with N,N-dimethylbenzylamines: site-selective oxidative CDC. Chem. Commun., 2018, vol. 54, no. 54, pp. 7511--7514. DOI: https://doi.org/10.1039/C8CC03396J

[52] Kumar P., Kumar S.A., Singh R., et al. Nickel catalyzed ipso-hydroxylation and subsequent cross dehydrogenative coupling of arylboronic acids with tertiary amines: a facile access to α-phenolated tertiary amines. Adv. Synth. Catal., 2018, vol. 360, iss. 9, pp. 1786--1789. DOI: https://doi.org/10.1002/adsc.201701625

[53] Gonzalez P.E., Sharma H.K., Chakrabarty S., et al. Triethylsiloxymethyl-N,N-dimethylamine, Et3SiOCH2NMe2: a dimethylaminomethylation (Mannich) reagent for O--H, S--H, P--H and aromatic C--H Systems. Eur. J. Org. Chem., 2017, vol. 2017, iss. 37, pp. 5610--5616. DOI: https://doi.org/10.1002/ejoc.201700902

[54] Mastalir M., Pittenauer E., Allmaier G., et al. Manganese-catalyzed aminomethylation of aromatic compounds with methanol as a sustainable C1 building block. J. Am. Chem. Soc., 2017, vol. 139, iss. 26, pp. 8812--8815. DOI: https://doi.org/10.1021/jacs.7b05253

[55] Mastalir M., Glatz M., Pittenauer E., et al. Rhenium-catalyzed dehydrogenative coupling of alcohols and amines to afford nitrogen-containing aromatics and more. Org. Lett., 2019, vol. 21, iss. 4, pp. 1116--1120. DOI: https://doi.org/10.1021/acs.orglett.9b00034

[56] Fang M., Fu E., Yuan Q., et al. A short synthesis of chiral macrocyclic dioxopolyamines derived from L-proline. Synth. Commun., 2002, vol. 32, iss. 23, pp. 3629--3635. DOI: https://doi.org/10.1081/SCC-120014977

[57] Wu K.-C., Lin Y.-S., Yeh Y.-S., et al. Design and synthesis of intramolecular hydrogen bonding systems. Their application in metal cation sensing based on excited-state proton transfer reaction. Tetrahedron, 2004, vol. 60, iss. 51, pp. 11861--11868. DOI: https://doi.org/10.1016/j.tet.2004.09.102

[58] Hon Y.-S., Chou Yu-Yu, Wu I-C. Dibromomethane as one-carbon source in organic synthesis: the Mannich base formation from the reaction of phenolic compounds with a preheated mixture of dibromomethane and diethylamine. Synth. Commun., 2004, vol. 34, iss. 12, pp. 2253--2267. DOI: https://doi.org/10.1081/SCC-120038509

[59] Hwang D.-R., Uang B.-J. A modified Mannich-type reaction catalized by VO(acac)2. Org. Lett., 2002, vol. 4, iss. 3, pp. 463--466. DOI: https://doi.org/10.1021/ol017229j

[60] Anwar H.F., Skattebøl L., Hansen T.V. Synthesis of substituted salicylamines and dihydro-2H-1,3-benzoxazines. Tetrahedron, 2007, vol. 63, iss. 40, pp. 9997--10002. DOI: https://doi.org/10.1016/j.tet.2007.07.064

[61] Locher C. Convenient preparation of some N-substituted 1,2,3,4-tetrahydro-isoquinolines lacking electron-donating substituents. Synth. Commun., 2001, vol. 31,iss. 19, pp. 2895--2911. DOI: https://doi.org/10.1081/SCC-100105660

[62] Rivera A., Rios-Motta J., Navarro M.A. 7-(Imidazolidin-1-ylmethyl)quinolin-8-ol: an unexpected product from a Mannich-type reaction in basic medium. Heterocycles, 2006, vol. 68, no. 3, pp. 531--537. DOI: https://doi.org/10.3987/COM-05-10642

[63] Rivera A., Yorley D., Gonzalez-Salas D., et al. X-ray and hydrogen-bonding properties of 1-((1H-benzotriazol-1-yl)methyl)naphthalene-2-ol. Molecules, 2009, vol. 14, iss 3, pp. 1234--1244. DOI: https://doi.org/10.3390/molecules14031234

[64] Rivera A., Maldonado M. Unexpected behavior of 6H,13H-5:12,7:14-dime-thanedibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA) toward phenols. Tetrahedron Lett., 2006, vol. 47, iss. 42, pp. 7467--7471. DOI: https://doi.org/10.1016/j.tetlet.2006.08.045

[65] Rivera A., Rios-Motta J., Trujillo G.P., et al. Simple one-pot synthesis of new derivatives of the macrocyclic aminal 1,3,7,9,13,15,19,21-octaazapentacyclo-[,7.19,13.115,19]octacosane (OAPO). Synth. Commun., 2013, vol. 43, iss. 6, pp. 791--799. DOI: https://doi.org/10.1080/00397911.2011.609956

[66] Rivera A., Quevedo R. Solvent-free Mannich-type reaction of tetraazatricyclododecane (TATD) with phenols. Tetrahedron Lett., 2013, vol. 54, iss. 11, pp. 1416--1420. DOI: https://doi.org/10.1016/j.tetlet.2012.12.116