THERMO-THICKENING COMPOUNDS FOR NON-POLAR LIQUID

Abstract

A bis-urea compound of general formula (IV):

##STR00001##

The compound is useful as a thermo-thickening agent in a non-polar liquid such as engine lubricating oil or thermosetting varnish. Also, a method for preparing the thermo-thickening compound. Further, a composition comprising the thermo-thickening compound and a non-polar liquid.

Claims

1-15. (canceled)

16. A method for thermo-thickening a composition comprising the addition to said composition of a compound of general formula (IV): ##STR00094## wherein: R.sub.a, R.sub.b, R.sub.c and R.sub.d are each independently selected from H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo; R.sub.1 and R.sub.2 are each independently selected from linear alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl and macromolecular groups, substituted or not substituted by one or more halo; R.sub.3, R.sub.3, R.sub.4, R.sub.4 R.sub.5, R.sub.5, R.sub.6 and R.sub.6 are each independently selected from H, alkyl, alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl, alkylaryl, arylalkyl, heteroarylalkyl or alkylheteroaryl, substituted or not substituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium or halo; Z.sub.1 and Z.sub.1 are each independently selected from O and S atoms; Z.sub.2 and Z.sub.2 are each independently selected from NH, O and S atoms; n represents a positive integer from 0 to 10; and optionally, * stands for a stereogenic center; provided that R.sub.1 and R.sub.2 does not represent both a methyl group.

17. The method according to claim 16, wherein the compound is of general formula (IV bis): ##STR00095## wherein R.sub.a, R.sub.b, R.sub.c, R.sub.d, R.sub.1, R.sub.2, R.sub.3, R.sub.3, R.sub.4, R.sub.4, Z.sub.1, Z.sub.1, Z.sub.2 and Z.sub.2 are as defined in claim 16.

18. The method according to claim 17, wherein in the compound of formula (IVbis), R.sub.a and R.sub.c are both H.

19. The method according to claim 16, wherein said composition is a non-polar liquid.

20. The method according to claim 16, wherein thermo-thickening is performed at a temperature ranging from 5 C. to 100 C.

21. The method according to claim 16, for further improving the cold flow property of a non-polar liquid.

22. A Compound of general formula (IV): ##STR00096## wherein: R.sub.a, R.sub.b, R.sub.c and R.sub.d are each independently selected from H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo; R.sub.1 and R.sub.2 are each independently selected from linear alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl and macromolecular groups, substituted or not substituted by one or more halo R.sub.3, R.sub.3, R.sub.4, R.sub.4 R.sub.5, R.sub.5, R.sub.6 and R.sub.6 are each independently selected from H, alkyl, alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl, alkylaryl, arylalkyl, heteroarylalkyl or alkylheteroaryl, substituted or not substituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium or halo; Z.sub.1 and Z.sub.1 are each independently selected from O and S atoms; Z.sub.2 and Z.sub.2 are each independently selected from NH, O and S atoms; n represents a positive integer from 0 to 10 and optionally, * stands for a stereogenic center; provided that R.sub.1 and R.sub.2 does not represent both a methyl group.

23. The compound according to claim 22, wherein n is equal to 0 (i.e. compounds having formula (IV bis)).

24. The compound according to claim 23, wherein Z.sub.1, Z.sub.1, Z.sub.2 and Z.sub.2 represent O atoms.

25. The compound according to claim 24, selected from: (2S,2S)-dihexyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-diheptyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dioctyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dioctyl 2,2-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dioctyl 2,2-((((4,6-dichloro-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dinonyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dinonyl 2,2-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-didecyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-diundecyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-didodecyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-didodecyl 2,2-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-ditridecyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-ditetradecyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dihexadecyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dihexadecyl 2,2-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dioctadecyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-dioctyl 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-pentadeuteriumphenylpropanoate); (2S,2S)-bis(12,12,12-tribromododecyl) 2,2-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-bis(12,12,12-tribromododecyl) 2,2-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); (2S,2S)-bis(12,12,12-tribromododecyl) 2,2-((((4,6-dichloro-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate); and (2S,2S)-bis(12,12,12-trichlorododecyl) 2,2-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate).

26. A composition comprising at least one compound of claim 22, and a non-polar liquid.

27. The composition according to claim 26, wherein the liquid is selected from an oil (or lubricant), a grease, a monomer, a thermosetting resin, a perfume or a fuel.

28. The composition according to claim 26, wherein the compound is at a concentration ranging from more than 0 to 5% by weight to the total weight of the composition.

29. A process for manufacturing a compound of formula (IV bis) according to claim 23, comprising reacting at least one ester ammonium salt of formula (A-1): ##STR00097## wherein R.sub.3 and R.sub.3 are each independently selected from H, alkyl, alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl, alkylaryl, arylalkyl, heteroarylalkyl or alkylheteroaryl, substituted or not substituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium or halo; R.sub.1 is each independently selected from linear alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl and heteroalkynyl group, substituted or not substituted by one or more halo; and X.sup. is an anion. with (a) either a diisocyanate of general formula (A-2bis): ##STR00098## wherein R.sub.a, R.sub.b, R.sub.c and R.sub.d are each independently selected from H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo; (b) or a mixture of reagents allowing the in situ preparation of diisocyanate of formula (A-2bis).

30. The process according to claim 29, further comprising a preliminary step of preparing ester ammonium salt of formula (A-1) by reacting an amino acid and an alcohol such as hydroxyalkane.

31. The method according to claim 16, wherein said composition is selected from an oil, a grease, a monomer, a thermosetting resin, a perfume or a fuel.

32. The method according to claim 16, wherein R.sub.b and R.sub.d are each independently selected from H, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 heteroalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 dialkylamino and halo.

33. The method according to claim 16, wherein R.sub.1 and R.sub.2 are each independently selected from linear alkyl or linear heteroalkyl group, said linear group being substituted or not substituted by one or more halo.

34. The method according to claim 16, wherein R.sub.3, R.sub.3, R.sub.4, R.sub.4, R.sub.5, R.sub.5, R.sub.6 and R.sub.6 are each independently selected from H, C.sub.1-C.sub.12 alkyl substituted by at least one aryl, said aryl being substituted or not substituted by one or more halo or deuterium.

35. The method according to claim 16, wherein n is equal to 0.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0243] FIG. 1 is a theoretical graph of the variation of the viscosity in function of the temperature for a liquid (dotted line) and for the same liquid comprising a thermo-thickening compound of the invention (solid line).

[0244] FIG. 2 is a graph showing the evolution of flow time in function of the temperature for dodecane and methylcyclohexane and corresponding solutions comprising H3C11Xyl.

[0245] FIG. 3 is a graph showing the relative viscosity in function of the temperature for dodecane or methylcyclohexane solutions comprising H3C7Xyl, H3C11Xyl or H3C15Xyl.

[0246] FIG. 4 is a graph showing the evolution of G and G modulus for a solution of H3C11Xyl in dodecane (4.1 g/L) in function of frequency (rad/s).

[0247] FIG. 5 is a graph showing the evolution of complex viscosity for a solution of H3C11Xyl in dodecane (4.1 g/L) in function of frequency (rad/s).

EXAMPLES

[0248] The present invention is further illustrated by the following examples.

[0249] Part 1: Chemistry

[0250] Abbreviations

[0251] Ala Alanine;

[0252] AcOEt Ethyl acetate;

[0253] Ar Aromatic group;

[0254] CDCl.sub.3 Chloroform;

[0255] DCM Dichloromethane;

[0256] DIEA N,N-Diisopropylethylamine;

[0257] DIPA Diisopropylamine;

[0258] DMSO Dimethylsulfoxyde;

[0259] ESI Electrospray Ionization;

[0260] eq. Equivalent;

[0261] HMPA Hexamethylphosphoramide;

[0262] HRMS High-resolution mass spectrometry;

[0263] LDA Lithium diisopropylamide;

[0264] Leu et i-Leu Leucine and iso-Leucine;

[0265] M Molar;

[0266] min Minute(s);

[0267] MS Mass spectrometry;

[0268] NMR Nuclear magnetic resonance;

[0269] PE Petroleum ether;

[0270] Phe Phenylalanine;

[0271] PhGly Phenylglycine;

[0272] PTSA p-Toluenesulfonic acid;

[0273] TDI Toluene diisocyanate;

[0274] THF Tetrahydrofurane;

[0275] THP Tetrahydropyrane.

[0276] Materials and Methods

[0277] All amino acids were purchased from Sigma-Aldrich or Alfa Aesar (99% purity) and used as received. TDI was purchased from Sigma Aldrich (purity98%) and was used directly. Chromatography-grade solvents were used as received. Dried CH.sub.2Cl.sub.2 and THF were obtained from an SPS solvent purification system (IT-Inc) and stored on 4 molecular sieves. NEt.sub.3 and DIEA were dried by distillation over CaH2 and stored over 4 molecular sieves.

[0278] NMR Spectroscopy

[0279] NMR spectra were recorded on a Bruker Avance 400, 300 or 200 spectrometers and calibrated to the residual solvent peak. Peaks are reported in ppm with their corresponding multiplicity (s: singlet; d: doublet, t: triplet; q: quartet; quint: quintet; hept: heptuplet; dt: doublet of triplets; td: triplet of doublets), integration, and respective J coupling constants are given in hertz.

[0280] HRMS Spectrometer

[0281] Exact mass measurements (HRMS) were obtained on TQ R30-10 HRMS spectrometer by ESI+ ionization and are reported in m/z for the major signal.

[0282] Flash Chromatography

[0283] The flash chromatography purification was made with a Grace Reveleris and columns of the same brand. The water was purified using a milli-Q system.

[0284] Fourier Transform InfraRed Spectroscopy (FT-IR)

[0285] FT-IR measurements were performed on a Nicolet iS10 spectrometer in a CaF2 cell of 1.0 mm pathlength and are corrected for air, solvent and cell absorption.

[0286] Rheology Measurements

[0287] Rheology measurements were performed on a Haake RS600 rheometer equipped with a sandblasted stainless steel cone/plate geometry with a 35 mm diameter, a 53 m gap and a 2 angle. The temperature is controlled with a Peltier thermostat.

[0288] Viscosimetry Measurements

[0289] Viscosimetry measurements were recorded using an Anton paar AMVn falling-ball microviscometer with a 0.16 mm diameter capillary, with three measurements at an angle of +20 and 20. Results are reported as an average of those six measurements.

Example 1

General Procedures for Preparing Ester Bis-Ureas

[0290] 1.1. Synthesis of Ester Ammonium Tosylate Salts (Preliminary Step)

##STR00056##

[0291] This synthesis was adapted from: S. Cantekin, H. M. M. ten Eikelder, A. J. Markvoort, M. A. J. Veld, P. A. Korevaar, M. M. Green; A. R. A. Palmans, E. W. Meijer, Angew. Chem. Int. Ed. 2012, 51, 6426-6431.

[0292] 1 eq. of amino acid, 1.1 eq. of alcohol and 1.1 eq. of PTSA.H.sub.2O were added to toluene (0.15M) and the mixture was stirred under reflux equipped with a Dean-Stark apparatus for 12 h. The mixture was then concentrated under reduced pressure and diluted in Et.sub.2O. The solution was put into ice to precipitate for a couple of hours. The precipitate was then filtered, washed with cold Et.sub.2O and dried under vacuum.

[0293] 1.2. Synthesis of Ester Bis-Ureas with a Toluene Spacer (Method A)

##STR00057##

[0294] This synthesis was adapted from: F. Lortie, S. Boileau, L. Bouteiller, C. Chassenieux, B. Dem, G. Ducouret, M. Jalabert, F. Laupretre, P. Terech, Langmuir 2002, 18, 7218-7222.

[0295] 2.2 eq. of the ammonium ester tosylate (obtained according to method as defined above) was dissolved in anhydrous THF (0.05 M) under argon. 2.2 eq. of NEt.sub.3 and 1 eq. of TDI were added to the mixture. The mixture was stirred at room temperature for 48 h. The mixture was then concentrated under reduced pressure and either purified by column chromatography or recrystallized from acetonitrile.

[0296] 1.3. Synthesis of Ester Bis-Ureas with Other Spacers (Method B)

##STR00058##

[0297] This synthesis was adapted from: I. Giannicchi, B. Jouvelet, B. Isare, M. Linares, A. Dalla Cort, L. Bouteiller, Chem. Commun. 2014, 50, 611-613.

[0298] Under argon atmosphere, a 70 mM solution of the diaminobenzene derivative and 2 eq. of DIEA in DCM was added at 2.5 mL/h to a 60 mM solution of 0.66 eq. of triphosgene in DCM. The mixture was stirred for 1 h after addition and a 0.3 M solution of 2.1 eq. of the ammonium ester tosylate and 6.3 eq. of DIEA in DCM was added to the mixture. The solution was concentrated under reduced pressure and the product was either purified by column chromatography or recrystallized from acetonitrile.

Example 2

Synthesis of Ester Ammonium Tosylate Salts

[0299] 2.2. Linear Compounds

[0300] 2.2.1. Synthesized from Phenylalanine

[0301] Hexyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00059##

[0302] Preparation was achieved following the preliminary step as described above, using commercially available hexanol and (S)-Phenylalanine. The product was obtained as a white powder.

[0303] Heptyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00060##

[0304] Preparation was achieved following the preliminary step as described above, using commercially available heptanol and (S)-Phenylalanine. 3.41 g (99%) of product were obtained as a white powder.

[0305] .sup.1-H NMR (400 MHz, CDCl.sub.3) 8.24 (s, 3H, NH3), 7.74 (d, 2H, ArH, J=7.8 Hz), 7.20-7.03 (m, 7H, ArH), 4.31-4.18 (m, 1H, NH3-CH), 3.94-3.77 (m, 2H, COOCH2), 3.24 (dd, 1H, NH3-CHCH2, J=14.0, 5.3 Hz), 3.04 (dd, NH3-CHCH2, 1H, J=14.0, 8.2 Hz), 2.32 (s, 3H, ArCH3), 1.37-1.07 (m, 12H, CH2), 1.07-0.97 (m, 2H, CH2), 0.88 (t, 3H, CH3, J=6.5 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 169.02, 141.70, 140.33, 134.48, 129.57, 128.92, 128.69, 127.34, 126.34, 54.34, 36.53, 32.07, 29.86, 29.80, 29.65, 29.50, 29.37, 28.23, 25.75, 22.83, 21.45, 14.25.

[0306] Octyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00061##

[0307] Preparation was achieved following the preliminary step as described above, using commercially available octanol and (S)-Phenylalanine. 5.94 g (95%) of product were obtained as a white powder.

[0308] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.44 (s, 3H, NH3), 7.50 (d, 2H, ArH, 2J=7.6 Hz), 7.38-7.02 (m, 7H, ArH), 4.25 (t, 1H, NH3-CH, .sup.2J=6.6 Hz), 3.99 (t, 2H, COOCH2, .sup.2J=6.3 Hz), 3.08 (AB spin sytem, 2H, NH3-CHCH2, .sup.2J=8.1 Hz), 1.80 (quin, 2H, COOCH2-CH2, .sup.2J=1.8 Hz), 2.27 (s, 3H, ArCH3), 1.39 (quin, 2H, COOCH2-CH2-CH2, .sup.2J=6.5 Hz), 1.30-1.00 (m, 10H, CH2), 0.85 (t, 3H, CH3, .sup.2J=7.0 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 169.01, 141.69, 140.33, 134.49, 129.56, 128.91, 128.67, 127.33, 126.33, 66.37, 54.33, 31.93, 29.28, 29.25, 28.21, 25.72, 22.77, 21.44, 14.22.

[0309] Nonyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00062##

[0310] Preparation was achieved following the preliminary step as defined above, using commercially available nonanol and (S)-Phenylalanine. 5.32 g (91%) of product were obtained as a white powder.

[0311] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.24 (s, 3H, NH3), 7.75 (d, 2H, ArH, .sup.2J=8.1 Hz), 7.19-7.03 (m, 7H, ArH), 4.30-4.20 (m, 1H, NH3-CH), 3.95-3.80 (m, 2H, COOCH2), 3.15 (AB spin sytem, 2H, NH3-CHCH2), 2.33 (s, 3H, ArCH3), 1.39-1.00 (m, 14H, CH2), 0.90 (t, 3H, CH3, .sup.2J=7.0 Hz).sup.13C NMR (101 MHz, CDCl.sub.3) 168.86, 141.53, 140.23, 134.32, 129.44, 128.79, 128.56, 127.22, 126.21, 66.26, 54.20, 36.39, 31.87, 29.44, 29.28, 29.21, 28.10, 25.60, 22.67, 21.31, 14.11.

[0312] Decyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00063##

[0313] Preparation was achieved following the preliminary step as defined above, using commercially available decanol and (S)-Phenylalanine. 3.22 g (59%) of product were obtained as a white powder.

[0314] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.24 (s, 3H, NH3), 7.75 (d, 2H, ArH, .sup.2J=8.1 Hz), 7.19-7.03 (m, 7H, ArH), 4.30-4.20 (m, 1H, NH3-CH), 3.95-3.80 (m, 2H, COOCH2), 3.15 (AB spin sytem, 2H, NH3-CHCH2), 2.33 (s, 3H, ArCH3), 1.39-1.00 (m, 16H, CH2), 0.90 (t, 3H, CH3, .sup.2J=7.0 Hz; .sup.13C NMR (101 MHz, CDCl.sub.3) 169.01, 141.67, 140.36, 134.47, 129.57, 128.92, 128.69, 127.35, 126.34, 66.39, 54.34, 36.53, 32.04, 29.71, 29.62, 29.46, 29.35, 28.23, 25.74, 22.82, 21.45, 14.25.

[0315] Undecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00064##

[0316] Preparation was achieved following the preliminary step as defined above, using commercially available undecanol and (S)-Phenylalanine. 2.13 g (82%) of product were obtained as a white powder.

[0317] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.24 (s, 3H, NH3), 7.75 (d, 2H, ArH, .sup.2J=8.1 Hz), 7.19-7.03 (m, 7H, ArH), 4.30-4.20 (m, 1H, NH3-CH), 3.95-3.80 (m, 2H, COOCH2), 3.15 (AB spin sytem, 2H, NH3-CHCH2), 2.33 (s, 3H, ArCH3), 1.39-1.00 (m, 18H, CH2), 0.90 (t, 3H, CH3, .sup.2J=7.0 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 169.01, 141.70, 140.33, 134.49, 129.57, 128.92, 128.67, 127.33, 126.34, 66.38, 54.34, 36.53, 32.06, 29.82, 29.79, 29.77, 29.63, 29.50, 29.36, 25.74, 22.83, 21.44, 14.25.

[0318] Dodecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00065##

[0319] Preparation was achieved following the preliminary step as defined above, using commercially available dodecanol and (S)-Phelylalanine 10.62 g (86%) of product were obtained as a white powder.

[0320] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.24 (s, 3H, NH3), 7.74 (d, 2H, ArH, J=8.2 Hz), 7.20-7.04 (m, 6H, ArH), 4.29-4.19 (m, 1H, NH3-CH), 3.93-3.77 (m, 2H, COOCH2), 3.24 (dd, 1H, NH3-CHCH2, J=14.0, 5.3 Hz), 3.04 (dd, 1H, NH3-CHCH2, J=14.0, 8.4 Hz), 2.32 (s, 3H, ArCH3), 1.38-1.08 (m, 14H, CH2), 1.08-0.96 (m, 2H, CH2), 0.89 (t, 3H CH3, J=6.8 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 169.02, 141.70, 140.31, 134.52, 129.56, 128.90, 128.65, 127.30, 126.33, 66.35, 54.34, 36.53, 32.05, 29.81, 29.78, 29.76, 29.62, 29.49, 29.35, 28.21, 25.73, 22.81, 21.43, 14.24.

[0321] Dodecyl (R)-Phenylalaninate Ammonium Tosylate Salt

##STR00066##

[0322] Preparation was achieved following the preliminary step as defined above, using commercially available dodecanol and (R)-Phenylalanine. 2.12 g (86%) of product were obtained as a white powder.

[0323] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.21 (s, 3H, NH3), 7.72 (d, 2H, ArH, .sup.2J=8.1 Hz), 7.18-7.03 (m, 7H, ArH), 4.30-4.16 (m, 1H, NH3-CH), 3.94-3.76 (m, 2H, COOCH2), 3.14 (AB spin sytem, 2H, NH3-CHCH2), 2.31 (s, 3H, ArCH3), 1.40-0.97 (m, 28H, CH2), 0.87 (t, 2H, CH3, .sup.2J=7.0 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 169.02, 141.70, 140.32, 134.52, 129.56, 128.91, 128.66, 127.31, 126.34, 66.36, 54.34, 36.53, 32.05, 29.76, 29.63, 29.49, 29.35, 28.22, 25.73, 22.82, 21.43, 14.24.

[0324] Tridecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00067##

[0325] Preparation was achieved following the preliminary step as defined above, using commercially available decanol and (S)-Phenylalanine. 4.14 g (88%) of product were obtained as a white powder.

[0326] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.18 (s, 3H, NH3), 7.76 (d, 2H, ArH, J=7.9 Hz), 7.23-7.05 (m, ArH, 7H), 4.27 (dd, NH3-CH, 1H, J=8.1, 5.3 Hz), 3.88 (m, 2H, COOCH2), 3.27 (dd, 1H, NH3-CHCH2, J=14.1, 5.3 Hz), 3.07 (dd, 1H, NH3-CHCH2, J=14.1, 8.2 Hz), 2.35 (s, 3H, ArCH3), 1.43-1.11 (m, 20H, CH2), 1.06 (q, 2H, CH2, J=7.7 Hz), 0.91 (t, 3H, CH3, J=6.6 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 141.69, 140.35, 134.45, 129.57, 128.93, 128.70, 127.36, 126.32, 66.40, 54.34, 29.84, 29.82, 29.80, 29.77, 29.63, 29.50, 29.36, 28.23, 25.75, 22.83, 21.45, 14.25.

[0327] Tetradecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00068##

[0328] Preparation was achieved following the preliminary step as defined above, using commercially available decanol and (S)-Phenylalanine. 1.47 g (33%) of product were obtained as a white powder.

[0329] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.24 (s, 3H, NH3), 7.74 (d, 2H, ArH, J=8.0 Hz), 7.21-7.02 (m, 7H, ArH), 4.24 (dd, 1H, NH3-CH, J=8.2, 5.3 Hz), 3.95-3.76 (m, 2H, COOCH2), 3.24 (dd, 1H, NH3-CHCH2, J=14.1, 5.3 Hz), 3.05 (dd, 1H, NH3-CHCH2, J=14.0, 8.2 Hz), 2.33 (s, 3H, ArCH3), 1.45-1.09 (m, 21H, CH2), 1.04 (q, 2H, CH2, J=7.7 Hz), 0.89 (t, 3H, CH3, J=6.7 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 141.70, 140.35, 134.45, 129.58, 128.93, 128.70, 127.36, 126.33, 66.40, 54.33, 29.85, 29.83, 29.81, 29.78, 29.64, 29.51, 29.37, 28.24, 25.75, 22.83, 21.45, 14.25.

[0330] Hexadecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00069##

[0331] Preparation was achieved following the preliminary step as defined above, using commercially available decanol and (S)-Phenylalanine. 5.84 g (92%) of product were obtained as a white powder.

[0332] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.21 (s, 3H, NH3), 7.72 (d, 2H, ArH, .sup.2J=8.2 Hz), 7.16-7.034 (m, 7H, ArH), 4.27-4.17 (m, 1H, NH3-CH), 3.91-3.77 (m, 2H, COOCH2), 3.12 (AB spin sytem, 2H, NH3-CHCH2), 2.31 (s, 3H, ArCH3), 1.35-1.06 (m, 28H, CH2), 0.86 (t, 3H, CH3, .sup.2J=7.0 Hz). .sup.13C NMR (101 MHz, CDCl.sub.3) 168.88, 141.56, 140.21, 134.34, 129.44, 128.79, 128.56, 127.22, 126.21, 66.26, 54.21, 36.40, 31.94, 29.73, 29.71, 29.68, 29.66, 29.52, 29.37, 29.24, 28.11, 25.62, 22.70, 21.32, 14.12.

[0333] Octadecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00070##

[0334] Preparation was achieved following the preliminary step as defined above, using commercially available 1-octadecanol and (S)-Phenylalanine. The product is obtained as a white powder.

[0335] 2.2.2. Synthesized from Other Aminoacids

[0336] Octyl (S)-d.sub.5-Phenylalaninate Ammonium Tosylate Salt

##STR00071##

[0337] Preparation was achieved following the preliminary step as defined above, using commercially available octanol and (S)-d.sub.5-Phenylalanine. 2.32 g (85%) of product were obtained as a white powder.

[0338] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.45 (s, 3H, NH3), 7.23 (d, 2H, ArH, .sup.2J=8.1 Hz), 6.84 (d, 2H, ArH, .sup.2J=8.0 Hz), 4.28 (t, 1H, NH3-CH, .sup.2J=6.9 Hz), 4.02 (t, 2H, COOCH2, .sup.2J=6.4 Hz), 3.10 (AB system, 2H, NH3-CHCH2), 2.29 (s, 3H, ArCH3), 1.48-1.34 (m., 2H, COOCH2CH2), 1.34-1.06 (m, 10H, CH2), 0.87 (t, 12H, CH3, .sup.2J=6.8 Hz) .sup.13C NMR (75 MHz, DMSO-d.sub.6) 127.81, 125.22, 65.27, 52.98, 35.78, 30.91, 28.23, 27.49, 24.82, 21.79, 20.48, 13.64.

[0339] 2.2.3. Halogen-Functionalized Compounds

[0340] 12-Tribromododecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00072##

[0341] Preparation was achieved following the preliminary step as defined above, using 12-tribromododecanol and (S)-phenylalanine. 6.57 g (85%) of product were obtained as a white powder.

[0342] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.41 (s, 3H, NH3), 7.50 (d, 2H, ArH, .sup.2J=8.0 Hz), 7.32 (q, 3H, ArH, .sup.2J=7.3 Hz), 7.22 (d, 2H, ArH, .sup.2J=7.1 Hz), 7.12 (d, 2H, ArH, .sup.2J=7.9 Hz), 4.29 (t, 1H, NH3-CH, .sup.2J=6.9 Hz), 4.02 (t, 2H, COOCH2, .sup.2J=6.4 Hz), 3.09 (AB spin sytem, 2H, NH3-CHCH2, .sup.2J=21.7 Hz), 2.96 (t, 2H, CBr3-CH2, .sup.2J=7.8 Hz), 2.29 (s, 3H, ArCH3), 1.68 (quin, 2H, COOCH2-CH2, .sup.2J=7.4 Hz), 1.50-1.08 (m, 16H, CH2). .sup.13C NMR (101 MHz, CDCl.sub.3) 169.02, 141.64, 140.35, 134.43, 129.56, 128.92, 128.70, 127.37, 126.30, 66.37, 60.06, 54.33, 42.77, 36.51, 29.65, 29.57, 29.45, 29.31, 28.21, 28.01, 25.72, 21.48. HRMS (ESI, m/z) 570.0044 [M].sup.+, 570.0035 calculated for C.sub.21H.sub.33Br.sub.3NO.sub.2.

[0343] 12-Trichlorododecyl (S)-Phenylalaninate Ammonium Tosylate Salt

##STR00073##

[0344] Preparation was achieved following the preliminary step as defined above, using 12-trichlorododecanol and (S)-phenylalanine. 617 mg (76%) of product were obtained as a white powder.

[0345] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.22 (s, 3H, NH3), 7.74 (d, 2H, ArH, .sup.2J=8.2 Hz), 7.21-7.07 (m, 7H, ArH), 4.35-4.20 (m, 1H, NH3-CH), 3.98-3.82 (m, 2H, COOCH2), 3.17 (AB spin sytem, 2H, NH3-CHCH2, .sup.2J=5.9 Hz), 2.67 (t, 2H, CC13-CH2, .sup.2J=8.0 Hz), 2.34 (s, 3H, ArCH3), 1.78 (quin, 2H, COOCH2-CH2, .sup.2J=7.4 Hz), 1.48-1.00 (m, 16H, CH2)..sup.13C NMR (101 MHz, CDCl.sub.3) 169.00, 141.62, 140.40, 134.46, 129.57, 128.94, 128.70, 127.37, 126.32, 66.37, 55.34, 54.35, 36.53, 29.65, 29.56, 29.44, 29.32, 28.48, 28.22, 26.53, 25.73, 21.47. HRMS (ESI, m/z) 436.1575 [M].sup.+, 436.1571 calculated for C.sub.21H.sub.33Cl.sub.3NO.sub.2.

Example 3

Symmetric Ester Bis-Ureas with Linear Alkyl Chains

[0346] 3.1. Bis-Ureas Synthetized from Phenylalanine (Phe)

[0347] H3C5Tol

##STR00074##

[0348] Preparation was achieved following the method A using hexyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 726 mg (85%) of a pure product were obtained as a white paste.

[0349] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.60 (s, 1H, NH), 7.81 (s, 1H, NH), 7.73 (d, 1H, ArH, J=2.2 Hz), 7.35-7.17 (m, 11H, ArH), 7.11 (dd, 1H, ArH, J=8.2, 2.2 Hz), 6.94 (d, 2H, NH, J=8.0 Hz), 6.28 (d, 1H, ArH, J=7.9 Hz), 4.58-4.45 (m, 2H, NHCH), 4.02 (t, 4H, COOCH2, J=6.5 Hz), 3.09-2.93 (m, 4H, NH3-CHCH2), 2.08 (s, 3H, ArCH3), 1.58-1.45 (m, 4H, CH2), 1.31-1.17 (m, 13H, CH2), 0.84 (t, 6H, CH3, J=6.8 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.20, 154.63, 154.48, 138.10, 137.80, 136.85, 136.78, 129.94, 129.13, 128.26, 126.58, 119.48, 111.64, 110.01, 64.46, 53.97, 53.73, 37.72, 37.56, 30.83, 27.99, 24.95, 21.94, 17.18, 13.82.

[0350] H3C6Tol

##STR00075##

[0351] Preparation was achieved following the method A using heptyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 823 mg (88%) of a pure product were obtained as a white paste.

[0352] .sup.1H NMR (400 MHz, DMSO-d.sub.6/THF-d.sub.8 2/1) 8.60 (s, 1H, NH), 7.81 (s, 1H, NH), 7.77 (s, 1H, ArH), 7.34-7.15 (m, 13H, ArH), 6.96 (d, 1H, NH, J=7.8 Hz), 6.90 (d, 1H, NH, J=8.3 Hz), 6.28 (d, 1H, ArH, J=8.0 Hz), 4.57 (h, 2H, NHCH, J=7.0 Hz), 4.04 (t, 4H, COOCH2, J=6.7 Hz), 3.12-2.92 (m, 4H, NH3-CHCH2), 2.11 (s, 3H, ArCH3), 1.62-1.48 (m, 4H, CH2), 1.26 (s, 16H, CH2), 0.87 (t, 6H, CH3, J=6.5 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6/THF-d.sub.8 2/1) 172.10, 154.58, 154.44, 138.39, 137.97, 136.96, 129.65, 129.10, 128.06, 126.37, 118.98, 114.60, 111.35, 109.69, 64.36, 53.95, 53.72, 38.04, 37.87, 31.43, 25.45, 22.18, 17.03, 13.58. HRMS (ESI, m/z) 723.4100 [M+Na].sup.+, 723.4092 calculated for C.sub.46H.sub.56N.sub.4O.sub.6Na.

[0353] H3C7Tol

##STR00076##

[0354] Preparation was achieved following the method A using heptyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile.

[0355] HRMS (ESI, m/z) 751.4405 [M+Na].sup.+, 751.4405 calculated for C.sub.43H.sub.60N.sub.4O.sub.6Na

[0356] H3C7Xyl

##STR00077##

[0357] Preparation was achieved following the method B using octyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dimethyl-1,3-diaminobenzen. The product is recrystallized in acetonitrile. 963 mg (61%) of a pure product were obtained as a white paste.

[0358] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 7.94 (s, 1H, ArH), 7.75 (s, 2H, NH), 7.36-7.15 (m, 10H, ArH and NH), 6.85 (s, 1H, ArH), 6.69 (d, 2H, ArH, .sup.2J=7.9 Hz), 4.49 (q, 2H, NHCH, .sup.2J=7.2 Hz), 4.00 (t, 4H, COOCH2, .sup.2J=6.5 Hz), 3.08-2.91 (m, NH3-CHCH2, 4H), 2.05 (s, 6H, ArCH3), 1.50 (q, 4H, COOCHC2CH2, .sup.2J=6.0 Hz), 1.30-1.15 (m, 20H, CH2), 0.85 (t, 6H, CH3, .sup.2J=6.7 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.27, 154.73, 136.87, 135.27, 131.20, 129.12, 128.22, 126.53, 122.40, 115.64, 64.42, 53.91, 37.74, 31.20, 28.59, 28.54, 28.01, 25.27, 22.06, 17.17, 13.90. HRMS (ESI, m/z) 765.4570 [M+Na].sup.+, 765.4562 calculated for C.sub.44H.sub.62N.sub.4O.sub.6Na.

[0359] H3C7Cl

##STR00078##

[0360] Preparation was achieved following the method B using octyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dichloro-1,3-diaminobenzene. The product is recrystallized in acetonitrile. 457 mg (55%) of pure product were obtained as a white powder.

[0361] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.91 (s, 1H, ArH), 8.21 (s, 2H, NH), 7.46 (s, 1H, ArH), 7.41 (d, 2H, J=7.7 Hz, ArH), 7.34-7.17 (m, 12H, ArH and NH), 4.49 (q, 2H, NHCH, J=7.7 Hz), 4.01 (t, 4H, COOCH2, J=6.2 Hz), 3.08-2.91 (m, 4H NH3-CHCH2), 1.55-1.42 (m, 4H, CH2), 1.30-1.13 (m, 20H, CH2), 0.83 (t, 6H, CH3, J=6.8 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.00, 153.90, 136.74, 135.43, 129.07, 128.28, 126.61, 114.37, 112.83, 64.52, 54.01, 37.48, 31.19, 28.59, 28.55, 28.00, 25.28, 22.06, 13.89. HRMS (ESI, m/z) 805.3468 [M+Na].sup.+, 805.3469 calculated for C.sub.42H.sub.56Br.sub.4Cl.sub.2N.sub.4O.sub.6Na.

[0362] H3C8Tol

##STR00079##

[0363] Preparation was achieved following the method A using nonyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 1.42 g (83%) of a pure product were obtained as a white paste.

[0364] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.58 (s, 1H, ArH), 7.75 (d, 2H, NH, .sup.2J=30.5 Hz), 7.35-7.15 (m, 10H, ArH), 7.10 (d, 1H, NH, .sup.2J=8.3 Hz), 6.92 (d, 2H, ArH, .sup.2J=7.9 Hz), 6.26 (d, 1H, NH, .sup.2J=7.9 Hz), 4.49 (p, 2H, NHCH, .sup.2J=7.3 Hz), 4.01 (t, 4H, COOCH2, .sup.2J=6.4 Hz), 3.06-2.92 (m, 4H, NH3-CHCH2), 2.07 (s, 3H, ArCH3), 1.55-1.44 (m, 4H, COOCH2-CH2), 1.30-1.15 (m, 24H, CH2), 0.85 (t, 3H, CH3, .sup.2J=6.9 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.18, 154.61, 154.46, 138.07, 137.78, 136.84, 136.78, 129.93, 129.11, 128.25, 126.57, 119.41, 111.58, 109.94, 64.44, 53.96, 53.73, 37.68, 37.52, 31.24, 28.84, 28.62, 28.01, 25.27, 22.06, 17.18, 13.91. HRMS (ESI, m/z) 779.4716 [M+Na].sup.+, 779.4718 calculated for C.sub.45H.sub.64N.sub.4O.sub.6Na.

[0365] H3C8Xyl

##STR00080##

[0366] Preparation was achieved following the method B using nonyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized in acetonitrile. 465 mg (59%) of a pure product were obtained as a white paste.

[0367] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 7.94 (s, 1H, ArH), 7.75 (s, 2H, NH), 7.36-7.15 (m, 10H, ArH and NH), 6.85 (s, 1H, ArH), 6.69 (d, 2H, ArH, .sup.2J=7.9 Hz), 4.49 (q, 2H, NHCH, .sup.2J=7.2 Hz), 4.00 (t, 4H, COOCH2, .sup.2J=6.5 Hz), 3.08-2.91 (m, NH3-CHCH2, 4H), 2.05 (s, 6H, ArCH3), 1.50 (q, 4H, COOCHC2CH2, .sup.2J=6.0 Hz), 1.30-1.15 (m, 24H, CH2), 0.85 (t, 6H, COOCH2, .sup.2J=6.7 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.27, 154.73, 136.87, 135.26, 131.19, 129.11, 128.22, 126.52, 122.38, 64.41, 53.90, 37.73, 31.25, 28.62, 28.00, 25.26, 22.07, 17.17, 13.91. HRMS (ESI, m/z) 793.4886 [M+Na].sup.+, 793.4875 calculated for C.sub.46H.sub.66N.sub.4O.sub.6Na.

[0368] H3C9Tol

##STR00081##

[0369] Preparation was achieved following the method A using decyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 1.42 g (83%) of a pure product were obtained as a white paste.

[0370] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.60 (s, 1H, ArH), 7.78 (d, 2H, NH, .sup.2J=28.8 Hz), 7.42-7.12 (m, 10H, ArH), 7.12 (d, 1H, NH, .sup.2J=6.9 Hz), 6.94 (d, 2H, ArH, .sup.2J=5.1 Hz), 6.28 (d, 1H, NH, .sup.2J=6.7 Hz), 4.59-4.44 (m, 2H, NHCH), 4.02 (t, 4H, COOCH2, .sup.2J=6.4 Hz), 3.06-2.92 (m, 4H, NH3-CHCH2), 2.09 (s, 3H, ArCH3), 1.58-1.45 (m, 4H, COOCH2-CH2), 1.30-1.15 (m, 28H, CH2), 0.86 (t, 3H, CH3, .sup.2J=6.9 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.17, 154.61, 154.46, 138.09, 137.79, 136.84, 136.78, 129.91, 129.11, 128.23, 126.55, 119.38, 111.58, 109.94, 64.44, 53.96, 53.73, 37.71, 37.55, 31.28, 28.93, 28.92, 28.90, 28.69, 28.64, 28.02, 25.28, 22.09, 17.18, 13.90. HRMS (ESI, m/z) 807.5029 [M+Na].sup.+, 807.5031 calculated for C.sub.47H.sub.88N.sub.4O.sub.6Na.

[0371] H3C10Tol

##STR00082##

[0372] Preparation was achieved following the method A using undecyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 1.82 g (99%) of a pure product were obtained as a white paste.

[0373] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.60 (s, 1H, ArH), 7.78 (d, 2H, NH, .sup.2J=27.5 Hz), 7.37-7.14 (m, 10H, ArH), 7.12 (d, 1H, NH, .sup.2J=6.7 Hz), 6.94 (d, 2H, ArH, .sup.2J=5.1 Hz), 6.28 (d, 1H, NH, .sup.2J=6.0 Hz), 4.59-4.44 (m, 2H, NHCH), 4.02 (t, 4H, COOCH2, .sup.2J=6.4 Hz), 3.06-2.92 (m, 4H, NH3-CHCH2), 2.09 (s, 3H, ArCH3), 1.58-1.45 (m, 4H, COOCH2-CH2), 1.30-1.15 (m, 32H, CH2), 0.86 (t, 3H, CH3, .sup.2J=6.9 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.16, 154.45, 138.10, 137.79, 136.84, 136.77, 129.90, 129.10, 128.22, 126.54, 119.36, 111.58, 109.94, 64.43, 53.95, 53.72, 37.71, 37.56, 31.29, 28.99, 28.90, 28.71, 28.65, 28.02, 25.29, 22.09, 17.18, 13.89.

[0374] H3C11Xyl

##STR00083##

[0375] Preparation was achieved following the method B using dodecyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized twice in acetonitrile. 1.49 g (62%) of a pure product were obtained as a white paste.

[0376] .sup.1H NMR (300 MHz, DMSO-d.sub.6/THF-d.sub.8 2/1) 7.95 (s, 1H, ArH), 7.75 (s, 2H, NH), 7.36-7.15 (m, 10H, ArH and NH), 6.85 (s, 1H, ArH), 6.70 (d, 2H, ArH, .sup.2J=7.6 Hz), 4.49 (q, 2H, NHCH, .sup.2J=6.7 Hz), 4.00 (t, 4H, COOCH2, .sup.2J=6.2 Hz), 3.08-2.91 (m, NH3-CHCH2, 4H),), 2.05 (s, 6H, ArCH3), 1.50 (q, 4H, COOCHC2CH2, .sup.2J=6.0 Hz), 1.30-1.15 (m, 36H, CH2), 0.85 (t, 6H, COOCH2, .sup.2J=6.7 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6/THF-d.sub.8 2/1) 173.59, 156.09, 138.36, 136.86, 132.38, 130.49, 129.43, 127.72, 123.84, 117.23, 65.74, 55.28, 39.42, 32.81, 30.56, 30.53, 30.51, 30.43, 30.24, 30.19, 29.52, 26.81, 25.65, 25.45, 25.25, 25.05, 23.56, 18.43, 14.99. HRMS (ESI, m/z) 877.5807 [M+Na].sup.+, 877.5814 calculated for C.sub.52H.sub.78N.sub.4O.sub.6Na.

[0377] H3C12Tol

##STR00084##

[0378] Preparation was achieved following the method A using tridecyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 757 mg (99%) of a pure product were obtained as a white paste.

[0379] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.58 (s, 1H, ArH), 7.79 (s, 1H, NH), 7.73 (s, 1H, NH), 7.35-7.14 (m, 11H, ArH), 7.09 (d, 2H, ArH, J=7.6 Hz), 6.92 (d, 2H, NH, J=8.2 Hz), 6.26 (d, 1H, ArH, J=7.9 Hz), 4.56-4.43 (m, 2H, NHCH), 4.00 (t, 4H, COOCH2, J=6.5 Hz), 2.99 (q, 4H, NH3-CHCH2, J=7.3, 6.4 Hz), 2.07 (s, 3H, ArCH3), 1.58-1.41 (m, 4H, CH2), 1.36-1.07 (m, 36H, CH2), 0.85 (t, 6H, CH3, J=6.6 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.16, 154.60, 138.09, 137.78, 136.84, 136.77, 129.90, 129.10, 128.22, 126.54, 119.37, 111.58, 109.95, 64.42, 53.96, 53.73, 37.69, 37.54, 31.29, 29.05, 29.02, 28.97, 28.89, 28.71, 28.64, 28.02, 25.28, 22.08, 17.18, 13.89. HRMS (ESI, m/z) 891.5964 [M+Na].sup.+, 891.5970 calculated for C.sub.53H.sub.80N.sub.4O.sub.6Na.

[0380] H3C13Tol

##STR00085##

[0381] Preparation was achieved following the method A using tetradecyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 746 mg (96%) of a pure product were obtained as a white paste.

[0382] .sup.1H NMR (400 MHz, DMSO-d.sub.6/THF-d8 2/1) 8.60 (s, 1H, ArH), 7.79 (d, 2H, NH, J=16.7 Hz), 7.38-7.15 (m, 10H, ArH), 6.96 (d, 1H, ArH, J=7.8 Hz), 6.90 (d, 1H, ArH, J=8.3 Hz), 6.28 (d, 1H, NH, J=8.0 Hz), 4.57 (dd, 2H, NHCH, J=14.9, 7.4 Hz), 4.03 (t, 4H, COOCH2, J=6.7 Hz), 3.12-2.94 (m, 4H, NH3-CHCH2), 2.11 (s, 3H, ArCH3), 1.64-1.46 (m, 4H, CH2), 1.43-1.06 (m, 40H, CH2), 0.87 (t, 6H, CH3, J=6.5 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6/THF-d8 2/1) 172.11, 154.58, 154.45, 138.39, 137.97, 136.96, 136.90, 129.66, 129.10, 128.07, 126.37, 118.99, 114.60, 111.37, 109.69, 64.38, 53.94, 53.72, 38.04, 37.86, 31.43, 31.43, 29.19, 29.06, 28.85, 28.16, 25.44, 22.18, 22.18, 17.04, 13.59. HRMS (ESI, m/z) 919.6298 [M+Na].sup.+, 919.6283 calculated for C.sub.55H.sub.84N.sub.4O.sub.6Na.

[0383] H3C15Tol

##STR00086##

[0384] Preparation was achieved following the method A using hexadecyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 2.01 g (93%) of a pure product were obtained as a white paste.

[0385] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.59 (s, 1H, NH), 7.81 (s, 1H, NH), 7.77 (d, 1H, ArH, J=2.2 Hz), 7.33-7.26 (m, 4H, ArH), 7.26-7.17 (m, 7H, ArH), 6.96 (d, 1H, ArH, J=7.8 Hz), 6.90 (d, 1H, NH, J=8.3 Hz), 6.27 (d, 1H, NH, J=7.9 Hz), 4.63-4.47 (m, 2H, NHCH), 4.03 (t, 4H, COOCH2, J=6.7 Hz), 3.11-2.94 (m, 4H, NH3-CHCH2), 2.10 (s, 3H, ArCH3), 1.60-1.48 (m, 4H, CH2), 1.37-1.18 (m, 52H, CH2), 0.87 (t, 6H, CH3, J=6.7 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.00, 154.48, 154.34, 138.25, 137.85, 136.84, 136.78, 129.57, 128.99, 127.98, 126.28, 118.93, 111.29, 109.62, 66.30, 66.08, 65.87, 65.65, 64.28, 53.84, 53.62, 37.90, 37.72, 31.31, 29.07, 29.03, 28.94, 28.73, 28.04, 25.32, 24.17, 23.97, 23.77, 22.07, 16.94, 13.51. HRMS (ESI, m/z) 835.5340 [M+Na].sup.+, 853.5344 calculated for C.sub.49H.sub.72N.sub.4O.sub.6Na.

[0386] H3C15Xyl

##STR00087##

[0387] Preparation was achieved following the method B using hexadecyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized twice in acetonitrile. 1.05 g (64%) of a pure product were obtained as a white paste.

[0388] .sup.1H NMR (400 MHz, DMSO-d.sub.6/THF-d8 2/1) 8.02 (s, 1H, ArH), 7.77 (s, 2H, NH), 7.33-7.15 (m, 12H, ArH), 6.83 (s, 1H, ArH), 6.71 (d, 2H, NH, J=8.0 Hz), 4.57 (q, 2H, NHCH, J=7.0 Hz), 4.02 (t, 4H, COOCH2, J=6.5 Hz), 3.02 (dd, NH3-CHCH2, 4H, J=6.6, 3.3 Hz), 2.08 (s, 6H, ArCH3), 1.60-1.45 (m, 4H, CH2), 1.39-1.13 (m, 62H, CH2), 0.87 (t, H, CH3, J=6.7 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6/THF-d8 2/1) 172.11, 154.61, 136.88, 135.36, 130.90, 129.01, 127.95, 126.24, 122.33, 115.73, 64.25, 53.80, 31.31, 29.07, 29.03, 28.94, 28.73, 28.70, 28.03, 25.32, 22.07, 16.95, 13.51. HRMS (ESI, m/z) 989.7085 [M+Na].sup.+, 989.7066 calculated for C.sub.60H.sub.94N.sub.4O.sub.6Na.

[0389] H3C17Tol

##STR00088##

[0390] Preparation was achieved following the method A using octodecyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 923 mg (92%) of a pure product were obtained as a white paste. The S enantiomer was synthesized as well (88% yield).

[0391] .sup.1H NMR (400 MHz, DMSO-d.sub.6/THF-d8 2/1) 8.60 (s, 1H, NH), 7.82 (s, 1H, NH), 7.77 (d, 1H, ArH, J=2.2 Hz), 7.34-7.17 (m, 12H, ArH), 6.97 (d, 1H, NH, J=7.9 Hz), 6.90 (d, 1H, NH, J=8.3 Hz), 6.29 (d, 1H, ArH, J=8.0 Hz), 4.64-4.48 (m, 2H, NHCH), 4.09-3.98 (m, 4H, COOCH2), 3.12-2.95 (m, 4H, NH3-CHCH2), 2.20-2.05 (m, 3H, ArCH3), 1.54 (p, 4H, CH2, J=6.5 Hz), 1.36-1.17 (m, 60H, CH2), 0.87 (t, 6H, CH3, J=6.7 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6/THF-d8 2/1) 172.10, 154.59, 154.44, 138.40, 137.98, 136.97, 136.91, 129.64, 129.10, 128.05, 126.36, 118.98, 111.37, 109.70, 64.36, 53.95, 53.73, 38.05, 37.87, 31.44, 29.20, 29.16, 29.08, 28.86, 28.17, 25.46, 25.44, 22.19.

[0392] H3C7d.sub.5-PheTol

##STR00089##

[0393] Preparation was achieved following the method A using octyl (S)-d.sub.5-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 649 mg (73%) of a pure product were obtained as a white paste.

[0394] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.59 (s, 1H, NH), 7.80 (s, 1H, ArH), 7.72 (s, 1H, NH), 7.10 (d, 1H, NH, .sup.2J=8.3 Hz), 6.93 (d, 2H, ArH, .sup.2J=7.4 Hz), 6.27 (d, 1H, NH, .sup.2J=8.1 Hz), 4.49 (qi, 2H, NHCH, .sup.2J=7.2 Hz), 4.01 (t, 4H, COOCH2, .sup.2J=6.5 Hz), 3.05-2.95 (m, 4H, COOCH2-CH2), 2.07 (s, 3H, ArCH3), 1.56-1.44 (m, 4H, COOCH2-CH2-CH2), 1.33-1.15 (m, 44H, CH2), 0.84 (t, 3H, CH3, .sup.2J=6.5 Hz). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.20, 154.62, 154.48, 138.10, 137.79, 136.66, 136.59, 129.93, 119.43, 111.61, 109.97, 64.45, 53.96, 53.74, 37.60, 37.44, 31.20, 28.60, 28.55, 28.02, 25.28, 22.06, 17.18, 13.89. HRMS (ESI, m/z) 761.5039 [M+Na].sup.+, 761.5033 calculated for C.sub.35H.sub.50D.sub.10N.sub.4O.sub.6Na.

[0395] 3.2. Halogen Functionalized Ester Bis-Ureas

[0396] Br3C11Tol

##STR00090##

[0397] Preparation was achieved following the method A using 12-tribromododecyl (S)-phenylalaninate ammonium tosylate salt. The product is recrystallized in acetonitrile. 2.04 g (84%) of a pure product were obtained as a white paste.

[0398] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.59 (s, 1H, NH), 7.80 (s, 1H, NH), 7.72 (d, 1H, ArH, .sup.2J=1.7 Hz), 7.36-7.02 (m, 11H, ArH and NH), 6.93 (d, 2H, ArH, .sup.2J=8.2 Hz), 6.27 (d, 2H, ArH, .sup.2J=7.7 Hz), 4.48 (p, 2H, NHCH, .sup.2J=7.0 Hz), 4.01 (t, 4H, COOCH2, .sup.2J=6.3 Hz), 3.06-2.90 (m, 8H, NH3-CHCH2 and CBr3-CH2), 2.07 (s, 3H, ArCH3), 1.67 (p, 4H, COOCH2-CH2, .sup.2J=7.5 Hz), 1.59-1.45 (m, 4H, ArO-CH2-CH2), 1.45-1.15 (m, 28H, CH2). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.17, 154.60, 138.08, 137.78, 136.84, 136.77, 129.93, 129.12, 128.25, 126.57, 119.38, 111.58, 109.92, 64.45, 58.68, 53.72, 43.37, 37.69, 37.54, 29.16, 28.86, 28.74, 28.62, 28.02, 27.08, 25.27, 17.22. HRMS (ESI, m/z) 1335.0275 [M+Na].sup.+, 1335.0247 calculated for C.sub.51H.sub.70Br.sub.6N.sub.4O.sub.6Na.

[0399] Br3C11Xyl

##STR00091##

[0400] Preparation was achieved following the method B using 12-tribromododecyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized in acetonitrile. 707 mg (28%) of a pure product were obtained as a white paste.

[0401] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 7.95 (s, 1H, ArH), 7.75 (s, 2H, NH), 7.35-7.15 (m, 13H, ArH and NH), 6.98-6.80 (m, 8H, ArH and NH), 6.85 (s, 1H, ArH), 6.70 (d, 2H, ArH, .sup.2J=7.8 Hz), 4.49 (q, 2H, NHCH, .sup.2J=7.2 Hz), 4.00 (t, 4H, COOCH2, .sup.2J=6.4 Hz), 3.05-2.90 (m, CBr3-CH2 and NH3-CHCH2, 8H), 2.05 (s, 6H, ArCH3), 1.67 (p, 4H, COOCH2-CH2, .sup.2J=7.3 Hz), 1.58-1.15 (m, 32H, CH2). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.26, 154.71, 144.47, 137.61, 136.86, 135.25, 131.18, 129.11, 128.22, 126.53, 122.38, 64.42, 58.65, 53.90, 43.37, 37.72, 29.15, 28.83, 28.71, 28.60, 28.00, 27.06, 25.25, 17.18. HRMS (ESI, m/z) 1349.0413 [M+Na].sup.+, 1349.0403 calculated for C.sub.52H.sub.72Br.sub.6N.sub.4O.sub.6Na.

[0402] Br3C11Cl

##STR00092##

[0403] Preparation was achieved following the method B using 12-tribromododecyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dichloro-1,3-diaminobenzene. The product is recrystallized in acetonitrile. 1.09 g (68%) of pure product were obtained as a white powder.

[0404] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 8.91 (s, 1H, ArH), 8.19 (s, 2H, NH), 7.50-7.12 (m, 13H, ArH and NH), 4.57-4.42 (m, 2H, NHCH), 4.00 (t, 4H, COOCH2, .sup.2J=4.7 Hz), 2.97 (m, NH3-CHCH2 and CBr3-CH2, 8H), 1.78-1.58 (m, 4H, COOCH2-CH2), 1.65-1.10 (m, 32H, CH2). .sup.13C NMR (101 MHz, DMSO-d.sub.6) 171.97, 153.86, 136.72, 135.42, 129.05, 128.26, 128.13, 126.59, 114.30, 112.77, 64.50, 58.67, 53.98, 43.36, 37.48, 29.15, 28.85, 28.73, 28.61, 27.99, 27.08, 25.27. HRMS (ESI, m/z) 1388.9324 [M+Na].sup.+, 1388.9311 calculated for C.sub.50H.sub.66Br.sub.6Cl.sub.2N.sub.4O.sub.6Na.

[0405] C13C11Xyl

##STR00093##

[0406] Preparation was achieved following the method B using 12-trichlorododecyl (S)-phenylalaninate ammonium tosylate salt and 4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized in acetonitrile. 291 mg (64%) of a pure product were obtained as a white paste.

[0407] .sup.1H NMR (300 MHz, DMSO-d.sub.6) 7.95 (s, 1H, ArH), 7.75 (s, 2H, NH), 7.35-7.15 (m, 15H, ArH and NH), 6.98-6.80 (m, 8H, ArH and NH), 6.85 (s, 1H, ArH), 6.70 (d, 2H, ArH, .sup.2J=7.8 Hz), 4.49 (q, 2H, NHCH, .sup.2J=7.2 Hz), 4.00 (t, 4H, COOCH2, .sup.2J=6.4 Hz), 3.04-2.94 (m, NH3-CHCH2, 4H), 2.72 (t, CC13-CH2, .sup.2J=7.9 Hz), 2.05 (s, 6H, ArCH3), 1.67 (p, 4H, COOCH2-CH2, .sup.2J=7.3 Hz), 1.58-1.15 (m, 32H, CH2). .sup.13C NMR (75 MHz, DMSO-d.sub.6) 172.76, 155.22, 137.37, 135.77, 131.69, 129.61, 128.72, 127.02, 122.89, 116.16, 101.03, 64.92, 54.62, 54.41, 38.25, 29.34, 29.31, 29.17, 29.11, 28.51, 27.98, 26.59, 25.77, 17.68. HRMS (ESI, m/z) 1083.3474 [M+Na].sup.+, 1083.3446 calculated for C.sub.52H.sub.72Cl.sub.6N.sub.4O.sub.6Na.

[0408] Part 2: Physico-Rheological Tests

Example 4

Effect of Temperature on Relative Viscosity

[0409] The aim of this experiment was to measure the effect of the temperature on the evolution of the relative viscosity of non-polar liquids.

[0410] Viscosity is a measure of a fluid's resistance to flow. In this experiment, the relative viscosity has been evaluated by measuring the flow time of the sample at various temperatures using 0.1 mM solution of H3C11Xyl either in methylcyclohexane or in dodecane.

[0411] The results (FIG. 2) show that: [0412] for the liquids onlyi.e. free of H3C11Xyl(dodecane or methylcyclohexane), the flow time dramatically decreases when the temperature increases until 120 C.; [0413] when H3C11Xyl is added to either dodecane or methylcyclohexane (non-polar liquid), the flow time is higher than the one of the corresponding solution without the compound of invention; [0414] in the temperature range from about 20 C. to 45 C. for the solution of H3C11Xyl in dodecane or in the range from about 22 C. to 55 C. for the solution of H3C11Xyl in methylcyclohexane, the flow time of solutions comprising H3C11Xyl does not decrease, and even slightly increases, when the temperature rises.

[0415] In conclusion, these experiments evidence that the compound of the invention (ester bis-ureas) acts as a thermo-thickening agent when added in a non-polar liquid such as dodecane or methylcycloxane.

Example 5

Influence of Alkyl Chain Length

[0416] The aim of this experiment is to investigate the influence of the length of the alkyl chain on the evolution of the relative viscosity by comparing an ester bis-urea with an octyl chain, a dodecyl chain and a hexadecyl chain.

[0417] This experiment is carried out by solubilizing in a non-polar liquid at a concentration of 0.1 mM: H3C7Xyl (ester bis-urea with octyl chain), H3C11Xyl (ester bis-urea with dodecyl chain) or H3C15Xyl (ester bis-urea with hexadecyl chain), as described above. The non-polar liquids are chosen among methylcyclohexane and dodecane.

[0418] The results (FIG. 3) show that for all solutions comprising an ester bis-ureas with octyl (H3C7Xyl), dodecyl (H3C11Xyl) or hexadecyl (H3C15Xyl) chain, the relative viscosity increases or is maintained when solutions are heated from 5 C. to about 70 C.

[0419] In conclusion, these experiments evidence that ester bis-ureas with long alkyl chains act as efficient thermo-thickening agent when added in a non-polar liquid heated at a temperature ranging from about 5 C. to 70 C.

Example 6

Rheology Test

[0420] The aim of this experiment is to show the rheology behavior of a composition of the invention.

[0421] For this purpose, the storage modulus (Gelastic response) and the loss modulus (Gviscous behavior) have been measured at 1 rad/s, for a solution of H3C11Xyl in dodecane (4.1 g/L). G and G allow having information regarding the complex viscosity of a sample.

[0422] The results (FIGS. 4 and 5) show that the complex viscosity increases by 1.5 for a solution comprising a compound of the invention heated at a temperature ranging from 20 C. to 50 C.