WO2013017714A1 - Compuestos organogelantes de alta temperatura - Google Patents

Compuestos organogelantes de alta temperatura Download PDF

Info

Publication number
WO2013017714A1
WO2013017714A1 PCT/ES2012/070545 ES2012070545W WO2013017714A1 WO 2013017714 A1 WO2013017714 A1 WO 2013017714A1 ES 2012070545 W ES2012070545 W ES 2012070545W WO 2013017714 A1 WO2013017714 A1 WO 2013017714A1
Authority
WO
WIPO (PCT)
Prior art keywords
isocyanate
general formula
compound
acid
solvents
Prior art date
Application number
PCT/ES2012/070545
Other languages
English (en)
Spanish (es)
French (fr)
Inventor
Santiago Vicente Luis Lafuente
Jenifer RUBIO MAGNIETO
Vicente MARTI CENTELLES
María Isabel BURGUETE AZCARATE
Original Assignee
Universitat Jaume I De Castelló
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universitat Jaume I De Castelló filed Critical Universitat Jaume I De Castelló
Publication of WO2013017714A1 publication Critical patent/WO2013017714A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/06—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton
    • C07C275/16—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/06—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton
    • C07C275/14—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/20—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C275/24—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/52—Amides or imides
    • C08F20/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
    • C08F20/60—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/09—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in organic liquids

Definitions

  • the present invention relates to the synthesis of new low molecular weight organogelling compounds capable of producing the gelation of organic solvents with implemented properties.
  • the gelation technique consists in trapping the solvent in a fibrillar network formed by organic molecules that interact with each other.
  • the mechanism of formation of the gels consists in the dissolution of these organic molecules in a solvent by heating them up to a certain temperature, this solution being called the sun phase.
  • the resulting solution is allowed to cool and as a result a gel is formed, called organogel when the trapped solvents are of the organic type, and hydrogel when this is water.
  • gelants are usually classified into two large groups: high molecular weight gelants, natural or synthetic macromolecules, and low molecular weight gelants.
  • organogels possess thermotropic characteristics, that is, the gel is destroyed above a temperature and it is passed to a liquid phase solution. In the ideal case, cooling that solution below the indicated temperature regenerates the organogel.
  • This thermal stability is directly related to the strength of the interaction of organic molecules in the fibrillar network. Greater thermal stability of the gel allows the maintenance of the gel structure in a greater range of temperatures.
  • To obtain a high thermal stability of the gel it is necessary that the interaction forces between the organic molecules that act as organogelants be high. These intermolecular interactions can be achieved by combining multiple complementary hydrogen bonds, such as those associated with amide and urea clusters that have high interaction energy. In addition to these hydrogen bond interactions, Van der Waals forces between the different alkyl groups in the molecule also play an important role in gel stability.
  • organogelants act as such for a very small number of solvents, usually belonging to structurally related families (ie aromatic solvents). This fact also hinders its technological application.
  • a characteristic example would be its application in cosmetics or in the controlled release of drugs, where in a given formulation liquid phases of a very diverse nature can coexist. In these two cases, the combination of this property with a high thermal stability of the gel is highly desirable, since this would facilitate its storage, transport and handling without the need to maintain strict temperature control.
  • Another important example of technological application would be the use for the development of NMR techniques based on dipole coupling. In this case the required information can only be obtained when the experiments are carried out on a series of gels formed by solvents of very diverse nature.
  • organogelants used as low molecular weight organogelants have a great structural variety (Hirst, AR; Escuder, B .; Miravet, JF; Smith, DK Angew. Chem. Int. Ed. 2008, 47, 8002-8018).
  • organogelants with amide groups and carbamate groups are described in the literature (Kim, TH; Kwon, NY; Lee, TS Tetrahedron Lett. 2010, 51, 5596-5600;), as well as urea groups (Steed, JW Chem Soc. Fiev. 2010, 39, 3686-3699).
  • Another type of organogelants described are the supramolecular complexes of cyclodextrins and substituted anilines.
  • organogelants are structurally complex and involve long synthesis procedures and low overall yields and, therefore, the application on an industrial scale is difficult.
  • these organogelants generally have low thermal stability, which decreases their use in some of the applications of scientific and industrial interest.
  • the present invention faces the problem of providing new molecules capable of gelling a wide variety of organic solvents, and that the gels formed exhibit high thermal stability.
  • the present invention solves the problem described by a family of new compounds of general formula (I) that act as low molecular weight organogelants for a wide variety of solvents and that provide a very stable gel at high temperatures. They also have the advantage that their synthesis is quick and simple, with high final yields. Finally, its gelling action is carried out by adding very small amounts to the corresponding solvent.
  • the present invention relates to a compound of general formula (I) (compound of the present invention)
  • G1 is an amine selected from 1,2-ethylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,5-pentylenediamine, 1,6-hexylenediamine, 2,6-diaminopyridine, 2,6-bis (aminomethyl ) pyridine, 1,3-bis (aminomethyl) benzene, cyclic aliphatic diamines, or branched aliphatic diamines,
  • R1 is a side chain of an amino acid selected from amino aminobutyl acid, aspartic acid, glutamic acid, alanine, arginine, asparagine, cyclohexylalanine, cysteine, dibenzylglycine, diphenylalanine, phenylalanine, phenylglycine, glycine, glutamine, histidine, Homophenylalanine, Isoleucine, Leucine, Lysine, Methionine, Naphthylalanine, Pipecolic Acid, Proline, Serine, Tyrosine, Threonine, Tryptophan or Valine,
  • R2 is the side chain of an isocyanate selected from 1-butyloxy-4-isocyanatobenzene, 1-isocyanate-4-pentylbenzene, 1-isocyanathaphthalene, butyl isocyanate, decyl isocyanate, 5-isocyanatoisophthalate dimethyl, dodecylcyanate, phenylisocyanate of methyl or octylisocyanate.
  • an isocyanate selected from 1-butyloxy-4-isocyanatobenzene, 1-isocyanate-4-pentylbenzene, 1-isocyanathaphthalene, butyl isocyanate, decyl isocyanate, 5-isocyanatoisophthalate dimethyl, dodecylcyanate, phenylisocyanate of methyl or octylisocyanate.
  • the present invention relates to a process for obtaining the compound of the present invention (of general formula I, as described above), which comprises reacting a pseudopeptide compound of general formula (II)
  • G1 is an amine selected from 1,2-ethylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,5-pentylenediamine, 1,6-hexylenediamine, 2,6-diaminopyridine, 2,6-bis (aminomethyl ) pyridine, 1,3-bis (aminomethyl) benzene, cyclic aliphatic diamines, or branched aliphatic diamines,
  • R1 is a side chain of an amino acid selected from aminoisobutyl acid, aspartic acid, glutamic acid, Alanine, Arginine, Asparagine, Cyclohexylalanine, Cysteine, Dibenzylglycine, Diphenylalanine, Phenylalanine, Phenylglycine, Glycine, Glutamine, Histidine, Homophecinazine, Isoofucinacin Lysine, Methionine, Naphthylalanine, Pipecolic Acid, Proline, Serine, Tyrosine, Threonine, Tryptophan or Valine,
  • R2 is the side chain of an isocyanate selected from 1-butyloxy-4-isocyanatobenzene, 1-isocyanate-4-pentylbenzene, 1-isocyanathaphthalene, butyl isocyanate, decyl isocyanate, 5-isocyanatoisophthalate dimethyl, dodecylcyanate, phenylisocyanate of methyl or octylisocyanate.
  • an isocyanate selected from 1-butyloxy-4-isocyanatobenzene, 1-isocyanate-4-pentylbenzene, 1-isocyanathaphthalene, butyl isocyanate, decyl isocyanate, 5-isocyanatoisophthalate dimethyl, dodecylcyanate, phenylisocyanate of methyl or octylisocyanate.
  • the base is selected from triethylamine, pyridine, or diisopropylethylamine.
  • the solvent is an aprotic organic solvent such as dichloromethane, CHCI 3 , toluene, THF, among others.
  • the present invention relates to a process for obtaining stable gels at temperatures above 80 e C of organic solvents comprising dispersing or dissolving at most 5% by weight of the compound of formula (I) according to the claim 1, in an organic solvent, heating at the boiling temperature of the dispersion to facilitate solubilization and then allowing to cool to obtain the gel.
  • the organic solvents are aromatic solvents, esters, halogenated solvents, or aprotic polar solvents.
  • the present invention relates to the use of the compound of the present invention (of general formula (I) as described above) for the gelation of organic solvents.
  • the organic solvents are aromatic solvents, esters, halogenated solvents, or aprotic polar solvents. Description of the figures
  • Figure 1 shows the 1 H NMR spectrum (500 MHz, 20 mM in DMSO-c / 6 ) of compound (2S) -2 - [(butylcarbamoyl) amino] -N- ⁇ 3 - [(2S) -2 - [(Butylcarbamoyl) amino] -3-phenylpropanamide] propyl ⁇ -3-phenylpropanamide at different temperatures.
  • 2S 2 -2 - [(butylcarbamoyl) amino] -N- ⁇ 3 - [(2S) -2 - [(Butylcarbamoyl) amino] -3-phenylpropanamide] propyl ⁇ -3-phenylpropanamide at different temperatures.
  • G1 is an amine selected from among the amines described in Table 3
  • R1 is a side chain of an amino acid selected from among the amino acids in Table 1
  • R2 is the side chain of an isocyanate as shown in Table 2.
  • Hph Homophenylalanine CH 2 CH 2 C 6 H5 lie Isoleucine CH 3 CHCH 2 CH 3 Leu Leucine CH 2 CH (C) 2 Lys Usine CH2CH2CH2CH2NH2 Met Methionine CH 2 CH 2 SCH 3
  • Val Valine CH (CH 3 ) 2 , R ' is the side chain of the isocyanate.
  • Table 2 shows some examples of possible structures.
  • the compounds of the general formula (I) were prepared by dissolving an equivalent of the compound of the general formula (II), and 2.2 equivalents of the isocyanate of the general formula (III) and a base (examples of bases capable of acting properly are : triethylamine, pyridine or diisopropylethylamine) in an appropriate aprotic organic solvent (a normally suitable solvent is CH 2 CI 2 , but the reaction proceeded effectively in other solvents: CHCI 3 , toluene, THF, etc.). The reaction was cooled to 0 e C for 15 minutes and then allowed to react for 12 hours at room temperature. After this time the product obtained was purified.
  • the presence of sufficiently long aliphatic chains was a factor that contributed significantly to explain the organogelative characteristics of the pseudopeptides.
  • the high temperature organogelling compounds of the present invention can be used in various sectors. These sectors include the food industry; the pharmaceutical industry; cosmetics, biomedicine, biochemistry and clinical medicine, or the sectors related to the preparation of intelligent materials and application in analytical processes or the preparation of electronic devices.
  • the pseudopeptide compound (compound of general formula (II)) (203.4 mg, 0.495 mmol) was dissolved in CH 2 Cl 2 HPLC and the reaction was placed in an ice bath to 0 and C. Then was added dropwise dropwise a mixture of dodecyl isocyanate (compound of general formula (I II)) (265.09 ⁇ _, 1.089 mmol) and triethylamine (152.48 ⁇ _, 1.089 mmol). After 15 minutes of the addition, the ice bath was removed. The mixture was allowed to stir overnight. The solvent was evaporated in the rotary evaporator and recrystallization was performed using hot isopropanol.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Dispersion Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Cosmetics (AREA)
PCT/ES2012/070545 2011-07-29 2012-07-18 Compuestos organogelantes de alta temperatura WO2013017714A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES201131333A ES2395979B1 (es) 2011-07-29 2011-07-29 Compuestos organogelantes de alta temperatura.
ESP201131333 2011-07-29

Publications (1)

Publication Number Publication Date
WO2013017714A1 true WO2013017714A1 (es) 2013-02-07

Family

ID=47625625

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES2012/070545 WO2013017714A1 (es) 2011-07-29 2012-07-18 Compuestos organogelantes de alta temperatura

Country Status (2)

Country Link
ES (1) ES2395979B1 (sv)
WO (1) WO2013017714A1 (sv)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015136311A1 (en) 2014-03-13 2015-09-17 The Secretary Of State For Health Antimicrobial conjugates, method for production and uses thereof
WO2024062180A1 (fr) * 2022-09-22 2024-03-28 Sorbonne Universite Organogélateurs biosourcés et organogels les contenant

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002088049A (ja) * 2000-09-07 2002-03-27 Tdk Corp 重合官能基含有アルキレンアミド誘導体、ゲル化剤およびコーティング体

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002088049A (ja) * 2000-09-07 2002-03-27 Tdk Corp 重合官能基含有アルキレンアミド誘導体、ゲル化剤およびコーティング体

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
B. ESCUDER ET AL.: "Organogel formation by coaggregation of adaptable amidocarbamates and their tetraamide analogues", LANGMUIR, vol. 21, 2005, pages 6776 - 6787, XP055078584 *
BURGUETE, M. L.; GALINDO, F.; GAVARA, R.; IZQUIERDO, M. A.; LIMA, J. C.; LUIS, S. V.; PAROLA, A. J.; PINA, F., LANGMUIR, vol. 24, 2008, pages 9795 - 9803
DATABASE CAPLUS [online] 27 March 2012 (2012-03-27), XP055099316, accession no. STN Database accession no. 2002:233084 *
HIRST, A. R.; COATES, 1. A; BOUCHETEAU, T. R.; MIRAVET, J. F.; ESCUDER, B.; CASTELLETTO, V.; HAMLEY, . W.; SMITH, D. K., J. AM. CHEM. SOC., vol. 130, 2008, pages 9113 - 9121
HIRST, A. R.; ESCUDER, B.; MIRAVET, J. F.; SMITH, D. K., ANGEW. CHEM. INT. ED., vol. 47, 2008, pages 8002 - 8018
I. ALFONSO ET AL.: "Structural diversity in the self-assembly of pseudopeptidic macrocycles", CHEMISTRY: A EUROPEAN JOURNAL, vol. 16, 2010, pages 1246 - 1255, XP055078573 *
J. RUBIO ET AL.: "Gemini amphiphilic pseudopeptides: Synthesis and preliminary study of their self-assembling properties", TETRAHEDRON LETTERS, vol. 51, no. 45, 2010, pages 5861 - 5867, XP027388074 *
KIM, T. H.; KWON, N. Y.; LEE, T. S., TETRAHEDRON LETT., vol. 51, 2010, pages 5596 - 5600
LI, Y.; LIU, J.; DU, G.; YAN, H.; WANG, H.; ZHANG, H.; AN, W.; ZHAO, W.; SUN, T.; XIN, F., PHYS. CHEM. B., vol. 114, 2010, pages 10321 - 10326
MAKAREVIC, J.; JOKIC, M.; FRKANEC, L.; KATALENIC, D.; ZINIC, M., CHEM. COMMUN., 2002, pages 2238 - 2239
STEED, J. W., CHEM. SOC. REV., vol. 39, 2010, pages 3686 - 3699
ZHAO, W.; LI, Y.; SUN, T.; YAN, H.; HAO, A.; XIN, F.; ZHANG, H.; AN, W.; KONG, L.; LI, Y., COLLOIDS SURFACES A, vol. 374, 2011, pages 115 - 120

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015136311A1 (en) 2014-03-13 2015-09-17 The Secretary Of State For Health Antimicrobial conjugates, method for production and uses thereof
WO2024062180A1 (fr) * 2022-09-22 2024-03-28 Sorbonne Universite Organogélateurs biosourcés et organogels les contenant
FR3140084A1 (fr) * 2022-09-22 2024-03-29 Sorbonne Universite Organogélateurs biosourcés et organogels les contenant

Also Published As

Publication number Publication date
ES2395979B1 (es) 2013-12-05
ES2395979A1 (es) 2013-02-18

Similar Documents

Publication Publication Date Title
ES2911186T3 (es) Formas cristalinas de aminolípidos
Nanda et al. Single amino acid based thixotropic hydrogel formation and pH-dependent morphological change of gel nanofibers
ES2730474T3 (es) Proceso para la preparación de ivacaftor y solvatos de este
ElShaer et al. Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin
Chen et al. Novel self-assembling peptide hydrogel with pH-tunable assembly microstructure, gel mechanics and the entrapment of curcumin
Liu et al. Structure–property relationship of a class of efficient organogelators and their multistimuli responsiveness
Hooper et al. Gelation by supramolecular dimerization of mono (urea) s
ES2879294T3 (es) Formas polimórficas de Belinostat y procesos para la preparación de las mismas
PT2754682T (pt) Método para o fabrico de copolímero de bloco
Yadav et al. DAP derived fatty acid amide organogelators as novel carrier for drug incorporation and pH-responsive release
Paikar et al. Influence of side-chain interactions on the self-assembly of discotic tricarboxyamides: a crystallographic insight
WO2013017714A1 (es) Compuestos organogelantes de alta temperatura
CN105478054A (zh) 一种萘酚衍生物季铵盐阳离子表面活性剂及其制备方法
Blokhina et al. Thermodynamic study of aceclofenac solubility, distribution and sublimation
Rubio et al. Synthesis and organogelating ability of bis-urea pseudopeptidic compounds
WO2017152821A1 (zh) 一种异喹啉类化合物、其中间体、制备方法和应用
Wu et al. Gelation induced reversible syneresis via structural evolution
Kenarkoohi et al. Synthesis of malonamide pseudopeptidic compounds using a pseudo five-component reaction and evaluation of their gelation properties
CN104478886A (zh) 一种富勒烯双加成氨基酸及其合成方法
CN104725389B (zh) 黑三棱内酯b衍生物及其制备方法和用途
Sazonova et al. Synthesis of GK-2, a dimeric dipeptide nerve growth factor mimetic and potential neuroprotective agent
Biswas et al. Structural sensitivity of peptoid-based low molecular mass organogelator
CN107176913A (zh) 轴手性联萘酚衍生物Gemini型两亲分子对映异构体及其制备方法和应用
SG194957A1 (en) Stable crystal modifications of dotap chloride
Haldar et al. Spontaneous physical gelation from functionally modified tripeptides [C16-Ser (OBz)-X-Ser (OBz)-C16] via supramolecularly assisted polarophobic association in diverse organic media

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12820150

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12820150

Country of ref document: EP

Kind code of ref document: A1