FIELD OF THE INVENTION

The invention relates to adamantane urea derivatives, method of their preparation and use of the compounds presented herein for anion sensing and anion extraction.

STATE OF THE ART

During the last few decades a significant scientific effort has been devoted to the development of new analytical tools for detecting and sensing anions. The reason for that lies in the important role anions play in chemical and biological processes (Supramolecular Chemistry of Anions, Bianchi, A.; Bowman- James, K.; Garcia- Espana, E., Eds., VCH Verlag: Weinheim 1997.). In the research oriented towards anion sensing a special emphasis has been put on finding suitable chemical compounds that can selectively recognize anions. In spite of that, there are not many patents that describe the use of a particular class of compounds in anion sensing.

One of the functional groups that can recognize and bind anions is the urea moiety. The urea (or thiourea) moiety has been used as a receptor in electrochemical, fluorescent and chromόgenic sensors by attachment to o-, m- and /?-phenylene (Kim, Y-J.; Kwak, H.; Lee, S.J.; Lee, J.S.; Kwon, H.J.; Nam, S.H.; Lee, K.; Kim, C, Tetrahedron, 2006, 62, 9635. Nishizawa, S.; Bϋhlmann, P.; Iwao, M.; Umezawa, Y., Tetrahedron Lett., 1995, 36, 6483. Fan, E.; Van Annan, S.A.; Kincaid, S.; Hamilton, A.D., J. Am. Chem. Soc, 1993, 115, 369.), naphthalene (Cho, E.J.; Moon, J.W.; Ko, S.V.; Lee, J. Y.; Kim, S.K.; Yoon, J.; Nam, K.C., J. Am. Chem. Soc, 2003, 125, 12376.), anthracene (Gunnlaugsson, T.; Davis, A.P.; Glynn, M., Chem. Commun., 2001, 2556. Kim, S.K.; Yoon, J., Chem. Commun., 2002, 770.), pyrene (Nishizawa, S.; Kaneda, H.; Uchida, T.; Terame, N., J Chem. Soc. Perkin Trans. 2, 1998, 2325. Schazmann, B.; Alhashimy, N.; Diamond, D., J. Am. Chem. Soc, 2006, 128, 8607), calix[4]arene (Vatsouro, L; Rudzevich, V.; Bohmer, V., Org. Lett., 2007, 9, 1375.), and antraquinone (Jose, D.A.; Kumar, D.K.; Ganguly, B.; Das, A., Org. Lett., 2004, 6, 3445.). In addition, urea moieties were incorporated to rigid spacers such as norbornene (Lowe, A.J.; Dyson, G.A.; Pfeffer, F.M., Org. Biomol. Chem. 2007, 5, 1343.). The invention laid down in the patent application WO2008114067 (Basaric, N.; Renic, M.; Majerski, K., September 25, 2008.) and the scientific paper (Renic, M.; Basaric, N.; Mlinaric-Majerski, K., Tetrahedron left. 2007, 48, 7873) describe the preparation of a series of adamantane dipyrromethanes and their use as anion sensors. In the described compounds, adamantane as a rigid spacer preorganises the sensor molecule, thus making it more selective to some anions. Thus, in the further development of anion receptors, the idea is to synthesise molecules containing adamantane as a rigid spacer and two urea moieties as binding sites substituted with suitable chromophores.

Adamantane derivatives of urea are compounds known for several decades. However, they have not been used as anion binders or sensors. Interest in adamantylurea derivatives was primarily initiated due to wide range of their biological activity. They show antiviral activity (DuPont, GB 1063366, March 30, 1967. Cilag Chemie, GB1287317 August 31, 1972. Richter, C; Pluss, K.; Feth, G., US3703537, November 21, 1972. Richter, C; Pluss, K.; Feth, G., US3755415, August 28, 1973. Richter, C; Pluss, K.; Feth, G., US3786056, January 15, 1974.) or antibacterial activity (Geigy AG JR, GBl 125559, August 28, 1968.). Furthermore, they are inhibitors of cholesterol acyltransferase enzyme (Oremus, V.; Shmakhovski, V.; Faberova, V.; Kakalik, L; Shmidtova, Lj., Zemanek, J.N., RU2216536, November 20, 2003.) or ACAT inhibitors and antioxidants (Sueda, N.; Yamada, K.; Yanai, M.; Miura, K.; Horigome, M.; Oshida, N.; Hiramoto, S.; Katsuyama, K.; Nakata, F.; Kinoshita, N.; Tsukada, Y., EP0665216, August 02, 1995.). Adamantylureas show TNF-alpha production inhibitory effect (Mita, S.; Suhara, H.; Ban, M.; Horiuchi, M., CA2325741, October 07, 1999.), making them useful therapeutic agents for autoimmune diseases such as rheumatoid arthritis (Ban, M.; Suhara, H.; Horiuchi, M.; Yamamoto, N.; Enomoto, H.; Inoue, H., EP1743885, January 17, 2007.). Adamantylureas are also known to have cardioregulatory and diuretic activity (UPJOHN Co, GB 1456175, November 17, 1976.) and are potent agents for the treatment of diseases caused by the degeneration of central nervous system such as Alzheimer's disease, Alzheimer-type senile dementia, Huntington's chorea, Pick's disease, tardive dyskinesia, etc. (Tamura, T.; Tsukamoto, S.; Ichihara, M.; Usuda, S.; Harada, M., JP63208590, August 30, 1980.). Also, a variety of applications of adamantane derivatives of benzenesulfonylureas (Hoechst, AG, GB1435385, May 12, 1976.) was found. They proved to be useful as hypoglycemic agents (Geigy AG JR, GB1024495, March 30, 1966. Hoechst AG, GBl 163171, September 04, 1969. Hoechst AG, GBl 185395, March 25, 1970. Weber, H.; Aumueller, W.; Weyer, R.; Muth, K., CH519477, February 29, 1972. Weber, H.; Aumueller, W.; Weyer, R.; Muth, K., CH520120, March 15, 1972. Beyer, R.; Aumueller, W.; Hitsel, V., KR8000451, May 29, 1980. Beyer, R.; Aumueller, W.; Hitsel, V., Schmidt, V., KR8000489, June 04, 1980.) for lowering blood sugar level in the treatment of diabetes mellitus (Hoechst AG, GB1437036, May 26, 1976.). The same application, lowering blood-sugar content, was found for the isoquinoline derivatives of adamantylureas (Kutter, E.; Griss, G.; Grell, W.; Kleemann, M., CH534159, February 28, 1973. Kutter, E.; Griss, G.; Grell, W.; Kleemann, M., CH540911, August 31, 1973. Kutter, E.; Griss, G.; Grell, W.; Kleemann, M., CH540258, September 28,

1973.).

Adamantylureas find application also in the preparation of memantine hydrochloride, potent N-methyl-D-aspartic acid (NMDA) receptor antagonist, drug for treating dementia (Zou, Y.; Zhu, J.; Xiong, X., CN1400205, May 03, 2003. Zhang, F.; Hu, M.; Zhao, L.; Ge, M.; US20070078283 April 5, 2007.). Adamantylurea derivatives are also valuable precursors in the preparation of adamantylamines, compounds with activity on the central nervous system, especially useful for the treatment of Parkinson's disease (Merz & Co, GB1393503, May 07, 1975.).

In addition to medicinal applications, adamantane derivatives of ureas are also useful as herbicides (Abdulla, R.F.; Samaritoni, J.G., HU38217, May 28, 1986.). Adamantylurea derivatives were transformed to nitrosourea derivatives (Matsumoto, A.; Murakami, M.; Satou, N.; Hashimoto, S.; Kawamura, T.; Ichikawa, K., JP53034790, March 31, 1978.) or were connected to the polymers used in lithography (Saraiya, S.; Patel, J.; Tao, T.; Ray, K.B.; Mikell, F.E.; Mulligan, J.L.; Kalamen, J.; Beckley, S.; Clark, E., US2007128546, June 7, 2007.).

Although there are numerous examples of adamantane urea derivatives, there are only few reports on adamantane bisurea derivatives. One report is describing a self- assembly of the compound having urea moieties substituted with pyrimidones (Keizer, H.M.; Gonzalez, J.J.; Segura, M.; Prados, P.; Sijbesma, R.P.; Meijer, E. W.; de Mendoza, J., Chem. Eur. J., 2005, 11, 4602.). In the other report nitrogen atoms of adamantane bisurea moiety are alkylated (Kas'yan, L. L; Karpenko, D. V.; Kas'yan, A. O.; Isaev, A. K., Zh. Org. Chim. 2005, 41, 678.). Also, diphenyl derivative of adamantane bisurea is described in patent document dealing with the nitration of adamantane (Smith, G. W.; Williams, H. D. US 3053907, November 21, 1958). However, neither in the patent nor in these two reports the examination of the anion binding is reported.

SUBJECT OF THE INVENTION

The subject of the invention is a new series of adamantane bisurea derivatives, methods of their preparation and their use for anion binding. In this invention, anions are as follows: F ^" , Cl ^" , Br ^" , acetate, HSO ₄ ^" , NO ₃ ^" and H ₂ PO ₄ ^" . In comparison with the adamantane dipyrromethane compounds, whose application for anion sensing is described in previous invention (N. Basaric, M. Renic, K. Majerski, WO2008114067, September 25, 2008.), bisurea derivatives that are subject matter of the present invention form anion complexes with much higher stability constants and show selectivity towards F ^" , acetate and H ₂ PO ₄ ^" .

DETAILED DESCRIPTION OF THE INVENTION

The subject of this invention is adamantane bisurea derivatives represented by general formula I:

wherein n and m are the same or different, and equal to 0, 1 or 2, and Ar is selected between the substituents from the following group:

wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ ; provided that if n = m = O, Ar is not unsubstituted phenyl, and provided that if n = 1, m = O, Ar is not unsubstituted phenyl.

Furthermore, the subject of the present invention is adamantane bisurea derivatives represented by general formula I:

wherein n and m are strictly different, and equal to 0, 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ ; provided that if n = 1, m = 0, Ar is not unsubstituted phenyl.

Furthermore, the subject of the present invention is the compounds represented by general formula I:

wherein n and m are the same or different, and equal to 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is the compounds represented by general formula I:

wherein n and m are strictly different, and equal to 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is the compounds represented by general formula I:

wherein n and m are the same or different, and equal to O, 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

I wherein n and m are strictly different, and equal to O, 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are the same or different, and equal to 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

I wherein n and m are strictly different, and equal to 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are the same or different, and equal to O, 1 or 2, and Ar is selected between the substituents from the following group:

wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are strictly different, and equal to O, 1 or 2, and Ar is selected between the substituents from the following group:

wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are the same or different, and equal to 1 or 2, and Ar is selected between the substituents from the following group:

wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are strictly different, and equal to 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are the same or different, and equal to O, 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are strictly different, and equal to 0, 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are the same or different, and equal to 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is also the compounds of general formula I:

wherein n and m are strictly different, and equal to 1 or 2, and Ar is selected between the substituents from the following group: wherein the substituent R is methyl, ethyl, propyl, butyl, pentyl, hexyl, vinyl, F, Cl, Br, CN, OCH ₃ , NO ₂ .

Furthermore, the subject of the present invention is a method of preparation of adamantane bisurea derivatives described herein and represented by general formula I.

The method of preparation of adamantane bisurea derivatives of general formula I comprises the step of condensation reaction of adamantane- 1,3 -diyl derivatives such as adamantane- 1, 3 -diisocyanate derivatives or adamantane- 1,3 -diamine derivatives, respectively, with amine or isocyanate derivatives, respectively. It also comprises the step of the isolation of the product by filtration and/or removal of the solvent from the reaction mixture by evaporation under reduced pressure, crystallization, filtration, washing of the crystals, and additional purification by crystallization. The method of preparation can be carried out in the following manner: By reaction of adamantane diisocyanate derivative with the appropriate amine, wherein adamantane diisocyanate derivative can be prepared in situ from the corresponding adamantane diacid, or prepared from diacid or other appropriate precursor and isolated prior to the reaction with amine,

or the method of preparation can be carried out by the reaction of adamantane diamine derivative with the appropriate isocyanate

The first described procedure comprises the step of the condensation of adamantane diisocyanate with the appropriate amine and the step of isolation of the product I from the reaction mixture. The condensation step of adamantane diisocyanates with p- toluidine has been studied (Pershin, V.V.; Gureev, N.G.; Zhitnikov, A.N., Khim. Tehn. Elem. Polup. Polim., 1982, 17-22.), but the products derived therefrom have neither been isolated nor described. Adamantane diisocyanates can be prepared from several precursors, and preferably from admantane diacids.

Diacid derivatives mentioned herein, wherein n = 0,1, are known (Novikov, S. S.; Hardin, A.P.; Butenko, L.N.; Novakov, I.A.; Radchenko, S.S., Izv. Akad. Nauk. SSSR Ser. Khim. 1976, 2597. Stetter, H.; Wulff, C, Chem. Ber., 1960, 93, 1366. ). Diacids, wherein n = 0,1,2, are transformed in situ into the known diisocyanates (Khardin, A.P.; Gureev, N.G.; Radchenko, S.S., Zh. Org. Khim. 1980, 16, 60. Zlobin, V.A.; Kosolapov, V.T.; Moiseev, I.K.; Tarasov, A.K., Izv. Vys. Uch. Zav. Khim. Khim. Tekh., 1984, 27, 401. Khardin, A. P.; Pershin, V. V., Zh. Vs. Khim. Obs. 1979, 24, 95.) according to the modification of the known procedure (Sakaeda, N.; Watanabe, R., JP01275550, November 06, 1989. Sasaki, T., JP54046762, April 12, 1979. Kosolapov, V.T.; Zlobin, V.A.; Ioganov, K.M.; Kukushkin, I.K, SU615064, July 15, 1978. Kosolapov, V.T.; Zlobin, V.A.; Ioganov, K.M.; Ofitserova, V.G.; Kukushkin, I.K., SU550381, March 15, 1977. Nadachi, Y.; Kokura, M., JP50088060, July 15, 1975. Keizer, H.M.; Gonzalez, J.J.; Segura, M.; Prados, P.; Sijbesma, R.P.; Meijer, E. W.; de Mendoza, J., Chem. Eur. J. 2005, 11, 4602.). Most of the aromatic amines mentioned herein are known and often commercially available.

General procedure for the preparation of adamantane bisureas following the first described procedure

In a reaction vessel under a stream of inert gas, preferably N ₂ or argon, one equivalent of adamantane diacid derivative is dissolved or suspended in the appropriate anhydrous solvent such as the following: toluene, xylene, THF, dimethoxyethane (DME, glyme), bis(2-methoxyethyl) ether (diglyme), DMF or DMSO and particularly toluene. Minimally two equivalents of base are added to the stirred solution or suspension. The base used herein can be, for example, tertiary amine or pyridine and preferably triethylamine.

Thereafter, two equivalents of diphenylphosphoryl azide (DPPA) are added to the reaction mixture and the reaction mixture is heated at elevated temperature, preferably at 80 °C, from several hours to several days.

Alternatively, adamantane diisocyanate prepared according to one of the above mentioned procedures is dissolved in the appropriate anhydrous solvent such as: toluene, xylene, THF, dimethoxyethane (DME, glyme), bis(2-methoxyethyl) ether (diglyme), DMF or DMSO, and particularly toluene. Thereafter, two equivalents of amine are added to the reaction mixture which contains diisocyanate. Amine can be added as a pure compound or dissolved/suspended in an appropriate solvent such as: toluene, xylene, THF, dimethoxyethane (DME, glyme), bis(2-methoxyethyl) ether (diglyme), DMF or DMSO, and particularly toluene. After the amine is added, the reaction mixture is heated at the elevated temperature, and preferably at 80 ⁰ C, from several hours to several days.

The solvent is removed from the reaction mixture by distillation under reduced pressure and the residue was treated with alcohol. The product in the crystal form is washed with water and alcohol, and if necessary additionally purified by recrystallization or washing from the appropriate solvent such as toluene, xylene, DMF, DMSO, dimethoxyethane (DME, glyme) or bis(2-methoxyethyl) ether (diglyme). The second described procedure comprises the step of condensation reaction of adamantane diamine with the appropriate isocyanate, and the step of isolation of the product represented by general formula I from the reaction mixture. Adamantane diamine derivatives used herein for preparation of compounds I are known (Aigami, K.; Inamoto, Y.; Takaishi, N.; Hattori, K.; Takatsuki, A.; Tamura, G., J Med. Chem. 1975, 18, 713. Smith, G. W.; Williams, H.D., J. Org. Chem. 1961, 26, 2207.) and can be prepared by hydrogenation or reduction with LiAlH ₄ from the corresponding diazides (Nissan, D. A., Synth. Commun. 2006, 36, 2113.), dicyanides (Mlinaric- Majerski, K.; Margeta, R.; Veljkovic, J., Synlett 2005, 2089.), or by hydrolysis of diamides (Gopalan, B.; Thomas, A.; Shah, D.M., PCT2006090244, August 31, 2006). Majority of aromatic isocyanates used for preparation of compounds I are known compounds, and in some cases commercially available. They can be prepared by Curtius rearrangement from the corresponding acids according to the described procedure (Asis, S. E.; Bruno, A.M.; Martinez, A.R.; Sevilla, M.V.; Gaozza, C.H.; Romano, A.M.; Coussio, J.D.; Ciccia G., Farmaco 1999, 54, 517. Organic Syntheses, Collective vol. 3, Wiley, New York, 1963, p.846. Rutherford, K.G.; Newman, S.N., J. Am. Chem. Soc. 1957, 79, 213. Creech, HJ. ; Franks, W.R., J. Am. Chem. Soc. 1938, 60, 127), or by electrophilic aromatic substitution with the alkylhalogenide isocyanate derivative (Kozhushko, B.N.; Lomakina, A.V.; Paliichuk, Y.A.; Shokol, V.A., Zh. Org. Khim. 1984, 20, 721.) or by reaction of an amine with phosgene (Cummings, R.T.; Krafft, G.A., Tetrahedron Lett. 1988, 29, 65. Fieser, L.; Creech, H.J.; J. Am. Chem. Soc. 1939, 61, 3502). The step of isolation of the compounds I comprises the removal of the product from the reaction mixture by filtration, and in some cases by crystallization from the appropriate solvent. General procedure for the preparation of adamantane bisureas following the second described procedure

In a reaction vessel under a stream of inert gas, preferably N ₂ or argon, one equivalent of adamantane diamine derivative is dissolved or suspended in the appropriate anhydrous solvent such as: toluene, xylene, THF, dimethoxyethane (DME, glyme), bis(2-methoxyethyl) ether (diglyme), DMF or DMSO, and particularly THF. A solution or suspension of aromatic isocyanate is added to the stirred reaction solution or suspension. Alternatively, the solution or the suspension of amine can be added to the solution or the suspension of isocyanate. The reaction mixture is heated at elevated temperature from several hours to several days. After the reaction is completed, the compounds I are precipitated in the form of crystals which are filtered off and washed with water and alcohol. In case when products do not precipitate, the majority of the solvent is removed from the reaction mixture by distillation under reduced pressure, and alcohol is added to initialize crystallization. When needed, the product is additionally purified by recrystallization or washing from the appropriate solvent such as toluene, xylene, DMF, DMSO, dimethoxyethane (DME, glyme) or bis(2-methoxyethyl) ether (diglyme).

In case that the reaction is carried out according to the first described procedure, adamantane diisocyanate derivatives comprise the following: 1,3- diisocyanatoadamantane, 1,3-diisocyanatomethyladamantane and l,3-bis(2- isocyanatoethyl)adamantane, and amine derivatives comprise the following: substituted aniline, substituted benzylamines, substituted 2-phenyl-l-aminoethane, 1- aminonaphthalene, or substituted 1-aminonaphthalene, 1-aminomethylnaphthalene, or substituted 1-aminomethylnaphthalene, l-(2-aminoethyl)naphthalene, or substituted 1 -(2-aminoethyl)naphthalene, 2-aminonaphthalene, or substituted 2- aminonaphthalene, 2-aminomethylnaphthalene, or substituted 2- aminomethylnaphthalene, 2-(2-aminoethyl)naphthalene, or substituted 2-(2- aminoethyl)naphthalene, 1-aminoanthracene, 1-aminomethylanthracene, l-(2- aminoethyl)anthracene, 2-aminoanthracene, 2-aminomethylanthracene, 2-(2- aminoethyl)anthracene, 9-aminoanthracene, 9-aminomethylanthracene, 9-(2- aminoethyl)anthracene, 1-aminopyrene, 1-aminomethylpyrene, l-(2- aminoethyl)pyrene.

In case that the reaction is carried out according to the second described procedure, adamantane diamine derivatives comprise the following: 1,3-diaminoadamantane, 1,3-diaminomethyladamantane and l,3-bis-(2-aminoethyl)adamantane, and isocyanate derivatives comprise the following: substituted phenylisocyanate, substituted benzylisocyanate, substituted 2-phenylethylisocyanate, 1 -naphthylisocyanate, or substituted 1 -naphthylisocyanate, 1-naphthylmethylisocyanate, or substituted 1- naphthylmethylisocyanate, 2-(l-naphthyl)ethylisocyanate or substituted 2-(l- naphthyl)ethylisocyanate, 2-naphthylisocyanate, or substituted 2-naphthylisocyanate, 2-naphthylmethylisocyanate, or substituted 2-naphthylmethylisocyanate, 2-(2- naphthyl)ethylisocyanate or substituted 2-(2-naphthyl)ethylisocyanate, 1- anthrylisocyanate, 1-anthrylmethylisocyanate, 2-(l-anthryl)ethylisocyanate, 2- anthrylisocyanate, 2-anthrylmethylisocyanate, 2-(2-anthryl)ethylisocyanate, 9- anthrylisocyanate, 9-anthrylmethylisocyanate, 2-(9-anthryl)ethylisocyanate, 1- pyrenylisocyanate, 1-pyrenylmethylisocyanate, and 2-(l-pyrenyl)ethylisocyanate. The subject of the present invention is also the use of the herein described compounds of general formula I for anion sensing. Adamantane bisurea compounds presented herein bind F ^" , Cl ^" , Br ^" , acetate, HSO ₄ ^" , NO ₃ ^" , and H ₂ PO ₄ ^" and particularly F ^" , acetate and H ₂ PO ₄ ^" . Binding of said anions is demonstrated by UV and fluorescence titration and illustrated in examples 17 and 18 and Figures 1-4. The anion binding is evidenced by the change of the absorbance or fluorescence intensity, and in some cases also by the change of the maximum of the absorbance or emission band.

The compounds represented by general formula I and mixtures containing at least one or more compounds of general formula I, together with organic or inorganic filler and/or carrier (for example, compounds of general formula I can be adsorbed on silica gel or bound to polymer resin, or be in a mixture with an inert component) are also used for anion sensing in chemical and/or biological processes by use of UV-vis or fluorescence spectroscopy.

The compounds represented by general formula I, and the mixtures containing at least one or more of the above mentioned compounds are also used for binding anions and extracting anions from aqueous solutions into the organic solutions.

EXAMPLE 1 l,3-bis-(3-phenylureido)adamantane ¹

In a round bottom flask (50 mL), under a stream of N ₂ , 1,3-adamantane dicarboxylic acid (200 mg, 0.89 mmol) is suspended in anhydrous toluene (10 mL) and triethylamine (275 μL, 1.96 mmol) is added. The suspension is stirred at room temperature for 45 min, and, than, diphenylphosphoryl azide (DPPA, 440 μL, 2.05 mmol) is added. The reaction mixture is heated at 40 ⁰ C for 1 h, and after that 4 h at the temperature of the reflux. To this mixture a solution of aniline (180 μL, 1.96 mmol) in 1 mL of dry toluene is added and refluxing is continued for 16 h. The solvent is removed on the rotational evaporator and the residue treated with methanol. The product in the crystal form is filtered off, washed with water and methanol, and dried in vacuum (100 mbar) at 60°C for Ih (206 mg, 57 % yield).

Colourless crystals; ¹ H NMR (DMSO-J ₆ , 300 MHz) <5/ppm 8.21 (br s, 2H, H-8), 7.33 (d, 4H, J=7.6 Hz, H-10), 7.19 (dd, 4H, J=7.3 Hz, J=7.6 Hz, H-11), 6.86 (t, 2H, J=7.3 Hz, H-12), 5.97 (br s, 2H, H-6), 2.19 (br s, 2H, H-5), 2.16 (br s, 2H, H-2), 1.79-1.96 (m, 8H, H-3), 1.55 (br s, 2H, H-I); ¹³ C (DMSO-J ₆ , 75 MHz) <5/ppm 154.00 (s, 2C, C- 7), 140.57 (s, 2C, C-9), 128.61 (d, 4C, C-10/11), 120.79 (d, 2C, C-12), 117.38 (d, 4C, C-10/11), 51.33 (t, 1C, C-5), 45.96 (s, 2C, C-4), 40.77 (t, 4C, C-3), 35.06 (t, 1C, C-I), 29.39 (d, 2C, C-2); IR (KBr) v _m Jcm ^A 1310 (m), 1552 (s), 1593 (s), 1640 (s), 2912 (m), 3309 (w), 3355 (m); HRMS calcd for C ₂₄ H ₂₈ N ₄ O ₂ +K 443.1844, found 443.1865.

¹ The IUPAC name for this compound is l,l'-(adamantane-l,3-ylene)-di(3,3'- phenyl)urea This adamantane bisurea derivative is not a subject of this invention. However, the use of this compound for sensing, binding and extraction of anions is certainly a subject of the present invention, hence its preparation procedure is described.

Example 2 l,3-bis-(3-phenylureidomethyl)adamantane

Following the procedure described in example 1, l,3-bis-(3- phenylureidomethyl)adamantane is obtained (260 mg, 76 %) from 1,3 -adamantane diacetic acid (200 mg, 0.79 mmol), triethylamine (245 μL, 1.74 mmol), DPPA (395 μL, 1.82 mmol) and aniline (160 μL, 1.74 mmol), in 10 mL of dry toluene.

Colourless crystals, mp 283-284 °C; ¹ H NMR (DMSOd ₆ , 600 MHz) δ/ppm 8.37 (br s, 2H, H-9), 7.37 (d, 4H, J=8.2 Hz, H-I l), 7.20 (dd, 4H, J=7.3 Hz, J=8.2 Hz, H-12), 6.87 (t, 2H, J=7.3 Hz, H-13), 6.12 (t, 2H, J=5.9 Hz, H-7), 2.84 (d, 4H, J=5.9 Hz, H-6) 2.03 (br s, 2H, H-2), 1.56 (br s, 2H, H-5), 1.43 (d, 4H, J=I 1.4 Hz, H-3), 1.36 (d, 4H, J=I 1.4 Hz, H-3), 1.19 (br s, 2H, H-I); ¹³ C (DMSO-J ₆ , 150 MHz) <5/ppm 155.36 (s, 2C, C-8), 140.59 (s, 2C, C-IO), 128.63 (d, 4C, C-11/12), 120.81 (d, 2C, C-13), 117.36 (d, 4C, C-11/12), 50.42 (t, 2C, C-6), 42.40 (s, 2C, C-4), 39.32 (t, 4C, C-3), 36.04 (t, 1C, C-I), 34.04 (t, 1C, C-5), 27.79 (d, 2C, C-2); IR (KBr) v _m jcm ^l 1238 (m), 1310 (m), 1552 (s), 1645 (s), 2907 (m), 3355 (m); HRMS calcd for C ₂₆ H ₃₂ N ₄ O ₂ +H 433.2598, found 433.2583.

This adamantane bisurea derivative is not a subject of this invention. However, the use of this compound for sensing, binding and extraction of anions certainly represents integral part of the present invention, hence its preparation procedure is described.

Example 3 l,3-bis-(3-benzylureido)adamantane:

Following the procedure described in example 1, l,3-bis-(3-benzylureido)adamantane is obtained (162 mg, 84 %) from 1,3-adamantane dicarboxylic acid (100 mg, 0.45 mmol), triethylamine (135 μL, 0.98 mmol), DPPA (220 μL, 1.03 mmol) and benzylamine (105 μL, 0.98 mmol), in 10 mL of dry toluene.

Colourless crystals, mp 263-264 °C; ¹ H NMR (DMSO-J ₆ , 300 MHz) <5/ppm 7.30 (dd, 4H, J=7.0 Hz, J=7.6 Hz, H- 12), 7.17-7.26 (m, 6H, H-I l, H-13), 6.08 (t, 2H, J=5.8 Hz, H-8), 5.71 (br s, 2H, H-6), 4.15 (d, 4H, J=5.8 Hz, H-9), 2.09 (br s, 2H, H-2), 2.05 (br s, 2H, H-5), 1.80 (br s, 8H, H-3), 1.49 (br s, 2H, H-I); ¹³ C (DMSO-J ₆ , 75 MHz) <5/ppm 156.98 (s, 2C, C-7), 140.99 (s, 2C, C-10), 128.22 (d, 4C, C-11/12), 126.97 (d, 4C, C-11/12), 126.51 (d, 2C, C-13), 51.07 (t, 1C, C-5), 46.72 (s, 2C, C-4), 42.51 (t, 2C, C-9), 41.12 (t, 4C, C-3), 35.15 (t, 1C, C-I), 29.45(d, 2C, C-2); IR (KBr) v^/crn ¹ : 1294 (w), 1567 (s), 1634 (s), 2902 (w), 3304 (m), 3371 (m); HRMS calcd for C ₂₆ H ₃₂ N ₄ O ₂ +H 433.2598, found 433.261.

Example 4 l,3-bis-[(3-benzylureido)methyl]adamantane

Following the procedure described in example 1, l,3-bis-[(3- benzylureido)methyl]adamantane is obtained (286 mg, 78 %) from 1,3-adamantane diacetic acid (200 mg, 0.79 mmol), triethylamine (245 μL, 1.74 mmol), DPPA (395 μL, 1.82 mmol) and benzylamine (190 μL, 1.74 mmol), in 10 mL of dry toluene.

Colourless crystals, mp 223-225 ⁰ C; ¹ H NMR (DMSO-J ₆ , 300 MHz) <5/ppm 7.27-7.35 (m, 4H, H-13), 7.17-7.27 (m, 6H, H- 12, H-14), 6.23 (t, 2H, J=5.9 Hz, H-9), 5.87 (t, 2H, J=5.7 Hz, H-7), 4.20 (d, 4H, J=5.9 Hz, H-10), 2.76 (d, 4H, J=5.7 Hz, H-6), 1.99 (br s, 2H, H-2), 1.52 (br s, 2H, H-5), 1.38 (d, 4H, J=I 1.6 Hz, H-3), 1.29 (d, 4H, J=I 1.6 Hz, H-3), 1.11 (br s, 2H, H-I); ¹³ C (DMSO-^ ₆ , 75 MHz) δ/ppm 158.33 (s, 2C, C-8), 140.97 (s, 2C, C-I l), 128.20 (d, 4C, C-12/13), 126.98 (d, 4C, C-12/13), 126.54 (d, 2C, C-14), 50.90 (t, 2C, C-6), 42.93 (t, 2C, C-10), 42.58 (s, 2C, C-4), 39.36 (t, 4C, C-3), 36.10 (t, 1C, C-I), 34.09 (t, 1C, C-5), 27.83 (d, 2C, C-2); IR (KBr) v _m jcm ^l : 1243 (w), 1562 (s), 1624 (s), 2912 (m), 3335 (m); HRMS calcd for C ₂₈ H ₃₆ N ₄ O ₂ +Na 483.2735, found 483.273.

Example 5 l,3-bis-[3-(l-naphthyI)ureido]adamantane

Following the procedure described in example 1, 1, 3 -bis- [3 -(I - naphthyl)ureido]adamantane is obtained (170 mg, 38 %) from 1,3-adamantane dicarboxylic acid (200 mg, 0.89 mmol), triethylamine (275 μL, 1.96 mmol), DPPA (440 μL, 2.05 mmol) and 1-aminonaphthalene (281 mg, 1.96 mmol), in 7 mL of dry toluene.

Colourless crystals, mp 233-234 °C; ¹ H NMR (DMSCW ₆ , 600 MHz) <S/ppm 8.36 (br s, 2H, H-8), 8.08 (d, 2H, J=8.6 Hz, H- 17), 8.03 (dd, 2H, J=LO Hz, J=7.7 Hz, H-14), 7.88 (dd, 2H, J=I.2 Hz, J=8.0 Hz, H-12), 7.48-7.56 (m, 6H, H-IO, H-15, H-16), 7.39 (t, 2H, J=8.0 Hz, H-I l), 6.56 (br s, 2H, H-6), 2.32 (br s, 2H, H-5), 2.21 (br s, 2H, H- 2), 1.99 (d, 4H, J=I Ll Hz, H-3), 1.93 (d, 4H, J=I Ll Hz, H-3), 1.60 (br s, 2H, H-I); ¹³ C NMR (DMSCW ₆ , 75 MHz) <5/ppm 154.51 (s, 2C, C-7), 135.31 (s, 2C, C-ar), 133.87 (s, 2C, C-ar), 128.58 (d, 2C, C-ar), 126.10 (d, 2C, C-ar), 125.90 (d, 2C, C-ar), 125.55 (d, 2C, C-ar), 125.39 (s, 2C, C-ar), 121.90 (d, 2C, C-ar), 121.29 (d, 2C, C-ar), 116.09 (d, 2C, C-ar), 51.70 (t, 1C, C-5), 46.17 (s, 2C, C-4), 40.98 (t, 4C, C-3), 35.25 (t, 1C, C-I), 29.62 (d, 2C, C-2); IR (KBr) v _m jcm ^l : 1222 (m), 1258 (m), 1542 (s), 1645 (s), 2912 (m), 3335 (m); HRMS calcd for C ₃₂ H ₃₂ N ₄ O^H 505.2598, found 505.2598.

Example 6 l,3-bis-[3-(2-naphthyl)ureido]adamantane

Following the procedure described in example 1, l,3-bis-[3-(2- naphthyl)ureido]adamantane is obtained (160 mg, 36 %) from 1,3-adamantane dicarboxylic acid (200 mg, 0.89 mmol), triethylamine (275 μL, 1.96 mmol), DPPA (440 μL, 2.05 mmol) and 2-aminonaphthalene (281 mg, 1.96 mmol), in 15 mL of dry toluene.

Colourless crystals, mp 259-260 ⁰ C; ¹ H NMR (DMSCW ₆ , 600 MHz) <5/ppm 8.46 (br s, 2H, H-8), 8.02 (d, 2H, J=1.7 Hz, H-10), 7.75 (d, 4H, J=8.6 Hz, H-15, H-17), 7.71 (d, 2H, J=8.0 Hz, H-12), 7.40 (dt, 2H, J=8.0 Hz, J=LO Hz, H- 13), 7.34 (dd, 2H, J=8.6 Hz, J=1.7 Hz, H-18), 7.29 (dt, 2H, J=8.0 Hz, J=LO Hz, H-14), 6.09 (br s, 2H, H-6), 2.27 (br s, 2H, H-5), 2.18 (br s, 2H, H-2), 1.96 (d, 4H, J=I 1.3 Hz, H-3), 1.88 (d, 4H, J=11.3 Hz, H-3), 1.58 (br s, 2H, H-I); ¹³ C NMR (DMSO-J ₆ , 150 MHz) <5/ppm 154.31 (s, 2C, C-7), 138.27 (s, 2C, C-ar), 134.03 (s, 2C, C-ar), 128.83 (s, 2C, C-ar), 128.43 (d, 2C, C-ar), 127.55 (d, 2C, C-ar), 126.93 (d, 2C, C-ar), 126.42 (d, 2C, C-ar), 123.69 (d, 2C, C-ar), 119.53 (d, 2C, C-ar), 112.50 (d, 2C, C-ar), 51.68 (t, 1C, C-5), 46.06 (s, 2C, C-4), 40.94 (t, 4C, C-3), 35.23 (t, 1C, C-I), 29.59 (d, 2C, C-2); IR (KBr) v _m jcm ^l 1222 (m), 1351 (m), 1557 (s), 1681 (s), 2912 (m), 3299 (m), 3613 (s); HRMS calcd for C ₃₂ H ₃₂ N ₄ O ₂ +H 505.2598, found 505.2562.

Example 7 l,3-bis-{[3-(l-naphthyl)ureido] methyl} adamantane

Following the procedure described in example 1, 1, 3 -bis- {[3 -(I - naphthyl)ureido]methyl} adamantane is obtained (290 mg, 69 %) from 1,3- adamantane diacetic acid (200 mg, 0.79 mmol), triethylamine (245 μL, 1,74 mmol), DPPA (395 μL, 1.82 mmol) and 1 -aminonaphthalene (250 mg, 1.74 mmol) in 7 mL of dry toluene.

Colourless crystals, mp 295-296 °C; ¹ H NMR (DMSO-J ₆ , 600 MHz) <S/ppm 8.53 (br s, 2H, H-9), 8.11 (d, 2H, J=8.4 Hz, H-18), 8.07 (d, 2H, J=7.6 Hz, H-15), 7.88 (dd, 2H, J=7.7 Hz, J=I Hz, H-13), 7.49-7.56 (m, 6H, H-I l, H-16, H-17), 7.40 (t, 2H, J=7.7 Hz, H- 12), 6.64 (t, 2H, J=5.9 Hz, H-7), 2.94 (d, 4H, J=5.9 Hz, H-6), 2.08 (br s, 2H, H-2), 1.61 (br s, 2H, H-5), 1.51 (d, 4H, J=I 1.7 Hz, H-3), 1.45 (d, 4H, J=I 1.7 Hz, H- 3), 1.31 (br s, 2H, H-I); ¹³ C NMR (DMSO-J ₆ , 150 MHz) <5/ppm 155.71 (s, 2C, C-8), 135.30 (s, 2C, C-ar), 133.69 (s, 2C, C-ar), 128.38 (d, 2C, C-ar), 125.94 (d, 2C, C-ar), 125.68 (d, 2C, C-ar), 125.32 (d, 2C, C-ar), 125.07 (s, 2C, C-ar), 121.60 (d, 2C, C-ar), 121.14 (d, 2C, C-ar), 115.69 (d, 2C, C-ar), 50.73 (t, 2C, C-6), 42.55 (s, 2C, C-4), 39.39 (t, 4C, C-3), 36.08 (t, 1C, C-I), 34.09 (t, 1C, C-5), 27.85 (d, 2C, C-2), IR (KBr) v _max /cm ^" ' 1238 (m), 1552 (s), 1624 (s), 2902 (m), 3330 (m); HRMS calcd for C ₃₄ H ₃₆ N ₄ O ₂ +H 533.2911, found 533.2904.

Example 8 l,3-bis-{[3-(2-naphthyl)ureido]methyl}adamantane

Following the procedure described in example 1, 1,3 -bis- {[3 -(2- naphthyl)ureido] methyl }adamantane is obtained (190 mg, 45 %) from 1,3- adamantane diacetic acid (200 mg, 0.79 mmol), triethylamine (245 μL, 1.74 mmol), DPPA (395 μL, 1.82 mmol) and 2-aminonaphthalene (250 mg, 1.74 mmol), in 15 mL of dry toluene.

Colourless crystals, mp 237-238 °C; ¹ H NMR (DMSO-J ₆ , 600 MHz) <5/ppm 8.63 (br s, 2H, H-9), 8.03 (d, 2H, J=2.0 Hz, H-I l), 7.77 (d, 4H, J=8.9 Hz, H-16, H-18), 7.72 (d, 2H, J=8.0 Hz, H-13), 7.39-7.43 (m, 4H, H-14, H-19), 7.30 (dt, 2H, J=8.0 Hz, J=Ll Hz, H- 15), 6.25 (t, 2H, J=6.0 Hz, H-7), 2.90 (d, 4H, J=6.0 Hz, H-6), 2.06 (br s, 2H, H-5), 1.59 (br s, 2H, H-2), 1.47 (d, 4H, J-11.7 Hz, H-3), 1.40 (d, 4H, J=I 1.7 Hz, H-3), 1.25 (br s, 2H, H-I); ¹³ C (DMSO-^ ₆ , 150 MHz) (5/ppm 155.52 (s, 2C, C-8), 138.27 (s, 2C, C-ar), 133.88 (s, 2C, C-ar), 128.68 (s, 2C, Car), 128.28 (d, 2C, C-ar), 127.41 (d, 2C, C-ar), 126.77 (d, 2C, C-ar), 126.22 (d, 2C, C-ar), 123.49 (d, 2C, C-ar), 119.38 (d, 2C, C-ar), 112.27 (d, 2C, C-ar), 50.52 (t, 2C, C-6), 42.49 (s, 2C, C-4), 39.39 (t, 4C, C-3), 36.09 (t, 1C, C-I), 34.14 (t, 1C, C-5), 27.85 (d, 2C, C-2); IR (KBr)

V _max /cm- ¹ : 1243 (m), 1557 (s), 1645 (s), 2902 (m), 3309 (w), 3340 (m); HRMS calcd for C ₃₄ H ₃₆ N ₄ O ₂ +H 533.2911, found 533.2903.

Example 9

1 ,3-bis- [3-(l-anthry l)ureido] adamantane

Following the procedure described in example 1, l,3-bis-[3-(l- anthryl)ureido]adamantane is obtained (171 mg, 63%) from 1,3 -adamantane dicarboxylic acid (100 mg, 0.45 mmol), triethylamine (135 μL, 0.98 mmol), DPPA

(220 μL, 1.03 mmol) and 1-aminoanthracene (190 mg, 0.98 mmol) in 10 mL of dry toluene.

Yellowish crystals; ¹ H NMR (DMSO-cfe, 600 MHz) <5/ppm 8.71 (s, 2H, H-Ar), 8.58 (br s, 2H, H-8), 8.54 (s, 2H, H-Ar), 8.04-8.11 (m, 6H, H-Ar), 7.70 (d, 2H, J=8.2 Hz, H-Ar), 7.51-7.55 (m, 4H, H-Ar), 7.42 (t, 2H, J=8.2 Hz, H-Ar), 6.67 (br s, 2H, H-6), 2.43 (br s, 2H, H-5), 2.26 (br s, 2H, H-2), 2.07 (d, 4H, J=I 1.3 Hz, H-3a), 1.99 (d, 4H, J=I 1.3 Hz, H-3b), 1.65 (br s, 2H, H-I); ¹³ C NMR (DMSO-J ₆ , 150 MHz) <5/ppm 154.24 (s, 2C, C-7), 134.95 (s, 2C, C-Ar), 131.89 (s, 2C, C-Ar), 130.88 (s, 2C, C-Ar), 130.65 (s, 2C, C-Ar), 128.16 (d, 2C, C-Ar), 127.75 (d, 2C, C-Ar), 126.50 (d, 2C, C- Ar), 125.75 (d, 2C, C-Ar), 125.68 (d, 2C, C-Ar), 125.65 (d, 2C, C-Ar), 124.57 (s, 2C, C-Ar), 121.61 (d, 2C, C-Ar), 119.55 (d, 2C, C-Ar), 113.76 (d, 2C, C-Ar), 51.61 (t, 1C, C-5), 46.02 (s, 2C, C-4), 40.86 (t, 4C, C-3), 35.14 (t, 1C, C-I), 29.49 (d, 2C, C-2); IR (KBr) Vmax/cm ^"1 1222 (w), 1262 (w), 1308 (w), 1347 (w), 1405 (m), 1457 (w), 1542 (s), 1645 (s), 2909 (m), 3337 (m); HRMS calcd for C ₄₀ H ₃₆ N ₄ O ₂ +Na 627.273, found 627.2703.

Example 10 l,3-bis-[3-(2-anthryl)ureido]adamantane

Following the procedure described in example 1, l,3-bis-[3-(2- anthryl)ureido]adamantane is obtained (226 mg, 84 %) from 1,3-adamantane dicarboxylic acid (100 mg, 0.45 mmol), triethylamine (135 μL, 0.98 mmol), DPPA (220 μL, 1.03 mmol) and 2-aminoanthracene (190 mg, 0.98 mmol) in 10 mL of dry toluene.

Yellowish crystals; ¹ U NMR (DMSO-J ₆ , 600 MHz) δ/ppm 8.58 (s, 2H, H-6), 8.43 (s, 2H, H-10), 8.32 (s, 2H, H-19), 8.22 (s, 2H, H-12), 7.95-8.02 (m, 6H, H-14/22, H-17, H-21), 7.45 (dt, 2H, J=6.9 Hz, J= 1.2 Hz, H- 15) 7.41 (dt, 2H, J=6.9 Hz, J= 1.2 Hz, H- 16), 7.37 (dd, 2H, J=9.0 Hz, J=2.0 Hz, H-14/22), 6.18 (br s, 2H, H-8), 2.32 (br s, 2H, H-5), 2.22 (br s, 2H, H-2), 2.00 (d, 4H, J= 10.9 Hz, H-3), 1.93 (d, 4H, J= 10.9 Hz, H- 3), 1.62 (br s, 2H, H-I); ¹³ C NMR (DMSO-ύ? ₆ , 150 MHz) <S/ppm 154.14 (s, 2C, C-7), 137.56 (s, 2C, C-ar), 132.28 (s, 2C, C-ar), 131.76 (s, 2C, C-ar), 129.84 (s, 2C, C-ar), 128.73 (d, 2C, C-ar), 128.09 (d, 2C, C-ar), 127.92 (s, 2C, C-ar), 127.54 (d, 2C, C-ar), 125.77 (d, 2C, C-ar), 125.48 (d, 2C, C-ar), 124.41 (d, 2C, C-ar), 123.97 (d, 2C, C-ar), 120.91 (d, 2C, C-ar), 110.50 (d, 2C, C-ar), 51.56 (t, 1C, C-5), 45.94 (s, 2C, C-4), 40.81 (t, 4C, C-3), 35.12 (t, 1C, C-I), 29.48 (d, 2C, C-2); IR (KBr) v _m jcm ^] 1222 (m), 1305 (m), 1547 (s), 1634 (s), 2912 (m), 3304 (m), 3386 (m); HRMS calcd for C ₄₀ H ₃₆ N ₄ O ₂ +H 605.2911, found 605.2883.

Example 11 l,3-bis-[3-(9-anthryl)ureido]adamantane

Following the procedure described in example 1, l,3-bis-[3-(9- anthryl)ureido]adamantane is obtained (20 mg, 10%) from 1,3-adamantane dicarboxylic acid (100 mg, 0.45 mmol), triethylamine (135 μL, 0.98 mmol), DPPA (220 μL, 1.03 mmol) and 9-aminoanthracene (190 mg, 0.98 mmol), in 10 mL of dry toluene.

Yellowish crystals, ¹ H NMR (DMSO-J ₆ , 600 MHz) <5/ppm 8.50 (br s, 2H, H-8/16), 8.33 (br s, 2H, H-8/16), 8.04-8.17 (m, 8H, H-I l, H-14), 7.45-7.60 (m, 8H, H-12, H- 13), 6.35 (br s, 2H, H-8), 2.31 (br s, 2H, H-2), 2.20 (br s, 2H, H-5), 1.88-2.04 (m, 8H, H-3), 1.57 (br s, 2H, H-I); HRMS calcd for C ₄₀ H ₃₆ N ₄ O ₂ +Na 627.273, found 627.2746.

Example 12 l,3-bis-{[3-(9-anthryl)ureido]methyl}adamantane

Procedure a) Following the procedure described in example 1, 1,3 -bis- {[3 -(9- anthry l)ureido] methyl }adamantane is obtained (19 mg, 9 %) from 1,3-adamantane diacetic acid (89 mg, 0.35 mmol), triethylamine (110 μL, 0.78 mmol), DPPA (175 μL,

0.81 mmol) and 9-aminoanthracene (150 μL, 0.78 mmol) in 10 mL of dry toluene. Procedure b) In a two-neck round bottom flask, under a stream of N ₂ , 1,3- bis(aminomethyl)adamantane dihydrochloride (259 mg, 0.97 mmol) is suspended in 75 mL of anhydrous THF and triethylamine (410 μL, 2.91 mmol) is added by use of a syringe. By use of a dropping funnel a solution of 9-anthraceneisocyanate (425 mg, 1.94 mmol) in 30 mL anhydrous THF is added over 30 min. The reaction mixture is stirred at room temperature for Ih and heated at reflux over night. The cooled reaction mixture is filtered by use of a sinter funnel to separate the precipitated product. The product is washed by THF, water and methanol, and dried in a vacuum (100 bar) at 60 °C for Ih to yield 420 mg (69%) of pure product.

Yellowish crystals, ¹ H NMR (DMSO-J ₆ , 300 MHz) δ/ppm 8.52 (br s, 2H, H-8/16), 8.49 (br s, 2H, H-8/16), 8.04-8.20 (m, 8H, H- 12, H-15), 7.46-7.58 (m, 8H, H-13, H- 14), 6.38 (br s, 2H, H-9), 2.93 (d, 4H, J=5.5 Hz, H-6), 2.10 (br s, 2H, H-2), 1.64 (br s, 2H, K-S), 1.54 (d, 4H, J=12.2 Hz, H-3a), 1.44 (d, 4H, J=12.2 Hz, H-3b), 1.32 (br s, 2H, H-I); ¹³ C NMR (DMSO-J ₆ , 75 MHz) δ/ppm 157.26 (s, 2C, C-8), 131.42 (s, 2C, C-Ar), 130.68 (s, 2C, C-Ar), 128.66 (s, 2C, C-Ar), 128.28 (d, 2C, C-Ar), 125.54 (d, 2C, C-Ar), 125.37 (d, 2C, C-Ar), 124.77 (d, 2C, C-Ar), 124.08 (d, 2C, C-Ar), 51.00 (t, 2C, C-6), 42.83 (s, 2C, C-4), 36.18 (t, 1C, C-I), 34.42 (t, 1C, C-5), 27.96 (d, 2C, C-2), C-3 is covered with the signal Of DMSO-J ₆ ; IR (KBr) v _m jcm ^l 1238 (m), 1552 (s), 1619 (s), 2902 (m), 3257 (m), 3319 (m); HRMS calcd for C ₄₂ H ₄₀ N ₄ O ₂ +H 633.3224, found 633.3207.

Example 13 l,3-bis-[3-(9-anthrylmethyl)ureido]adamantane

Following the procedure described in example 1, l,3-bis-[3-(9- anthrylmethyl)ureido]adamantane is obtained (71 mg, 79%) from 1,3-adamantane dicarboxylic acid (100 mg, 0.45 mmol), triethylamine (135 μL, 0.98 mmol), DPPA (220 μL, 1.03 mmol) and 9-aminomethylanthracene (213 mg, 0.98 mmol) in 10 mL of dry toluene.

Yellowish crystals; ¹ H NMR (DMSO-J ₆ , 600 MHz) <5/ppm 8.59 (s, 2H, H-17), 8.41 (d, 2H, J=8.8 Hz, H-12), 8.11 (d, 2H, J=8.3 Hz, H-15), 7.59 (dd(t), 4H, J=7.2 Hz, H- 13/14), 7.53 (dd(t), 4H, J=7.4 Hz, H-13/14), 6.10 (t, 2H, J=5.3 Hz, H-8), 5.53 (br s, 2H, H-6), 5.15 (d, 4H, J=5.3 Hz, H-9), 2.08 (br s, 2H, H-2), 1.99 (br s, 2H, H-5), 1.78 (br s, 8H, H-3), 1.49 (br s, 2H, H-I); IR (KBr) v _m jcm ^l 1225 (w), 1292 (w), 1338 (w), 1357 (w), 1560 (s), 1623 (s), 2910 (m), 3345 (m); HRMS calcd for C ₄₂ H ₄₀ N ₄ O ₂ +Na 655.3043, found 655.3061.

Example 14 l,3-bis-{[3-(l-anthryl)ureido]methyl}adamantane

Following the procedure described in example 1, l,3-bis-{[3-(l- anthryl)ureido] methyl }adamantane is obtained (112 mg, 45%) from 1,3-adamantane diacetic acid (100 mg, 0.40 mmol), triethylamine (120 μL, 0.87 mmol), DPPA (195 μL, 0.91 mmol) and 1 -aminoanthracene (170 mg, 0.87 mmol) in 10 mL of dry toluene.

Yellowish crystals, ¹ H NMR (DMSO-J ₆ , 300 MHz) δ/ppm 8.79 (br s, 2H, H-Ar), 8.74 (br s, 2H, H-9), 8.54 (br s, 2H, H-Ar), 8.02-8.15 (m, 6H, H-Ar), 7.70 (d, 2H, J=8.3 Hz, H-Ar), 7.47-7.57 (m, 4H, H-Ar), 7.42 (t, 2H, J=7.9 Hz, H-Ar), 6.79 (t, 2H, J=5.2 Hz, H-7), 3.00 (d, 4H, J=5.2 Hz, H-6) 2.11 (br s, 2H, H-5), 1.64 (br s, 2H, H-2), 1.53 (t, 8H, J=I 3.1 Hz, H-3), 1.38 (br s, 2H, H-I); ¹³ C NMR (DMSO-J ₆ , 75 MHz) δ/ppm 155.78 (s, 2C, C-8), 135.05 (s, 2C, C-Ar), 131.90 (s, 2C, C-Ar), 130.90 (s, 2C, C-Ar), 130.65 (s, 2C, C-Ar), 128.95 (d, 2C, C-Ar), 128.18 (d, 2C, C-Ar), 127.77 (d, 2C, C- Ar), 126.55 (d, 2C, C-Ar), 125.77 (d, 2C, C-Ar), 125.68 (d, 2C, C-Ar), 124.59 (s, 2C, C-Ar), 121.73 (d, 2C, C-Ar), 119.60 (d, 2C, C-Ar), 113.90 (d, 2C, C-Ar), 50.78 (t, 2C, C-6), 42.57 (s, 2C, C-4), 36.12 (t, 1C, C-I), 34.15 (t, 1C, C-5), 27.88 (d, 2C, C-2), (the signal of C-3 is covered with the signal of DMSO-d ₆ ); IR (KBr) v _m jcm ^l 1238 (m), 1558 (s), 1653 (s), 2906 (m), 3366 (m); HRMS calcd for C ₄₂ H ₄₀ N ₄ O ₂ +Na 655.3043, found 655.3019.

Example 15

1 ,3-bis- [3-(l-py renyl)ureido] adamantane

Following the procedure described in example 1, l,3-bis-[3-(l- pyrenyl)ureido] adamantane is obtained (146 mg, 50%) from 1,3 -adamantane dicarboxylic acid (100 mg, 0.45 mmol), triethylamine (135 μL, 0.98 mmol), DPPA (220 μL, 1.03 mmol) and 1 -aminopyrene (213 mg, 0.98 mmol) in 10 mL of dry toluene.

Dark crystals, ¹ H NMR (DMSO-J ₆ , 300 MHz) <S/ppm 8.84 (br s, 2H, H-8), 8.71 (d, 2H, J=8.6 Hz, H-Ar), 8.33 (d, 2H, J=9.2 Hz, H-Ar), 8.16-8.25 (m, 8H, H-Ar), 7.97- 8.10 (m, 6H, H-Ar), 6.72 (br s, 2H, H-6), 2.45 (br s, 2H, H-5), 2.27 (br s, 2H, H-2), 2.10 (d, 4H, J=I 1.2 Hz, H-3a), 2.01 (d, 4H, J=I 1.2 Hz, H-3b), 1.66 (br s, 2H, H-I); ¹³ C NMR (DMSO-J ₆ , 75 MHz) δ/ppm 154.25 (s, 2C, C-7), 134.31 (s, 2C, C-Ar), 131.20 (s, 2C, C-Ar), 130.65 (s, 2C, C-Ar), 128.92 (d, 2C, C-Ar), 127.39 (d, 2C, C- Ar), 126.48 (d, 2C, C-Ar), 126.22 (d, 2C, C-Ar), 125.75 (d, 2C, C-Ar), 125.68 (d, 2C, C-Ar), 125.57 (s, 2C, C-Ar), 125.37 (d, 2C, C-Ar), 125.01 (d, 2C, C-Ar), 124.64 (d, 2C, C-Ar), 124.58 (s, 2C, C-Ar), 124.35 (s, 2C, C-Ar), 124.10 (d, 2C, C-Ar), 120.90 (d, 2C, C-Ar), 119.68 (s, 2C, C-Ar), 118.67 (d, 2C, C-Ar), 51.66(t, 1C, C-5), 46.01 (s, 2C, C-4), 40.86 (t, 4C, C-3), 35.15 (t, 1C, C-I), 29.51 (d, 2C, C-2); HRMS calcd for C ₄₄ H ₃₆ N ₄ O^Na 675.273, found 675.2719.

Example 16 l,3-bis-{[3-(l-pyrenyl)ureido]methyl}adamantane

Following the procedure described in example 1, 1, 3 -bis- {[3 -(I - pyrenyl)ureido] methyl }adamantane is obtained (150 mg, 55%) from 1,3-adamantane diacetic acid (100 mg, 0.45 mmol), triethylamine (135 μL, 0.98 mmol), DPPA (220 μL, 1.03 mmol) and 1-aminopyrene (213 mg, 0.98 mmol), in 10 mL of dry toluene.

Dark crystals, ¹ H NMR (DMSCW ₆ , 600 MHz) δ/ppm 8.96 (br s, 2H, H-9), 8.71 (d, 2H, J=8.3 Hz, H-Ar), 8.32 (d, 2H, J=9.3 Hz, H-Ar), 8.14-8.23 (m, 8H, H-Ar), 7.98- 8.07 (m, 6H, H-Ar), 6.75 (t, 2H, J=5.7 Hz, U-T), 3.02 (d, 4H, J=5.7 Hz, H-6), 2.13 (br s, 2H, H-5), 1.66 (br s, 2H, H-2), 1.57 (d, 4H, J=I 1.6 Hz, H-3a), 1.52 (d, 4H, J=I 1.6 Hz, H-3b), 1.40 (br s, 2H, H-I); IR (KBr) v _m jcm ^l 1239 (m), 1559 (s), 1623 (s), 2899 (m), 3337 (m); HRMS calcd for C ₄₆ H ₄₀ N ₄ O ₂ +Na 703.3043, found 703.3066.

Example 17

ANION BINDING TEST:

UV-vis titrations: The anion receptor of general formula I is dissolved in CH ₃ CN or DMSO in the concentration range 10 ^"4 - 10 ^"5 M, corresponding to the maximum of absorbance in the range 0.5-1.5. The solution of the receptor is placed in a quartz cuvette (1 mL) and small volumes (5-20 μL) of the following solutions of anion are added: Bu ₄ NF (1 M in THF, containing <wt 5 % H ₂ O, diluted with CH ₃ CN or DMSO to IxIO ^'3 M), Bu ₄ NCl, Bu ₄ NBr, Bu ₄ NOAc, Bu ₄ NHSO ₄ , Bu ₄ NNO ₃ or Bu ₄ NH ₂ PO ₄ (from I xIO ^"2 to I xIO ^"5 M in CH ₃ CN or DMSO). After each addition, UV-vis spectra are recorded. The titrations are performed at room temperature, 20 °C. From the UV- vis spectra, a calibration diagram is constructed showing the dependence of the absorbance on the concentration of anion. From the measured absorbance of the anion sample, an unknown concentration of anion can be determined. The results obtained from anion binding test are shown in figures 1-3.

Example 18

ANION BINDING TEST: Fluorescence titration: The anion receptor of general formula I is dissolved in CH ₃ CN or DMSO in the concentration range 10 ^~5 - 10 ^~6 M, corresponding to the maximum of absorbance in the range 0.08-0.1. The solution of the receptor is placed in a quarc cuvette (1 mL) and small volumes (5-20 μL) of the following solutions of anion are added: Bu ₄ NF (1 M in THF, containing <wt 5 % H ₂ O, diluted with CH ₃ CN or DMSO to I xIO ^"3 M), Bu ₄ NCl, Bu ₄ NBr, Bu ₄ NOAc, Bu ₄ NHSO ₄ , Bu ₄ NNO ₃ or Bu ₄ NH ₂ PO ₄ (from I xIO ^"2 to I xIO ^"5 M in CH ₃ CN or DMSO). After each addition the fluorescence spectra are recorded using the appropriate excitation wavelength. The titrations are performed at room temperature, 20 °C. From the fluorescence spectra a calibration diagram is constructed showing the dependence of the fluorescence intensity on the concentration of anion. From the measured fluorescence intensity of the anion sample, an unknown concentration of anion can be determined. The results obtained from anion binding test are shown in figure 4.

Figure 1 illustrates UV-vis spectra (CH ₃ CN) of adamantane bisurea of general formula I, wherein n = 1, m = 0, Ar = Ph (c = 6.29><10 ^"5 M), without the presence of anion, and with increasing concentrations OfBu ₄ NF.

Figure 2 illustrates UV-vis spectra (CH ₃ CN) of adamantane bisurea of general formula I, wherein n = 0, m = 0, Ar = 1-naphthyl (c = 8.3 ^χ lθ ^"5 M), without the presence of anion, and with increasing concentrations OfBu ₄ NH ₂ PO ₄ .

Figure 3 illustrates UV-vis spectra (DMSO) of adamantane bisurea of general formula I, wherein n = 1, m = 0, Ar = 9-anthryl (c = 5.84 ^χ lO ^"5 M), without the presence of anion, and with increasing concentrations of Bu ₄ NOAc. Figure 4 illustrates fluorescence spectra (DMSO, λ _exc = 370 nm) of adamantane bisurea of general formula I, wherein n = 1, m = 0, Ar = 9-anthryl (c = 6.41 ^χ lθ ^~5 M), without the presence of anion, and with increasing concentrations OfBu ₄ NF.