FR2997951A1 - New bis(aza-crown ethers) comprising aza-crown ether and diaza-crown ether interconnected by carbon arm connecting the nitrogen atom of aza-crown ether and nitrogen atoms of diaza-crown ether, useful as phase transfer catalyst - Google Patents

Abstract

Bis(aza-crown ethers) (Q) are new. (Q) comprise aza-crown ether and diaza-crown ether interconnected by at least one carbon arm connecting the nitrogen atom of the aza-crown ether and one of the nitrogen atoms of the diaza-crown ether, where second nitrogen atom of diaza-crown ether comprises hydrogen or carbon chain. Bis(aza-crown ethers) (Q) of formula (I) or (II) are new. (Q) comprise aza-crown ether and diaza-crown ether interconnected by at least one carbon arm connecting the nitrogen atom of the aza-crown ether and one of the nitrogen atoms of the diaza-crown ether, where second nitrogen atom of diaza-crown ether comprises hydrogen or carbon chain. X1, Y1 : H or carbon chain having 1-4 atoms; m : 1, 2, 3, 4, 5 or 6 (preferably 3 or 4); n : 1, 2 or 3 (preferably 1 or 2); p : 1, 2 or 3 (preferably 2); y : 5-30 (preferably 16-26); and Z : 3, 4, 5, 6, 7, 8, 9 or 10 (preferably 3, 4, 5 or 6). Independent claims are included for: (1) an intermediate compound comprising bis(aza-crown ethers) of formula (IV), (V) or (VII); and (2) preparing (Q). GP : amine protecting group. [Image] [Image].

Description

Field of the Invention The present invention relates to novel crown ether compounds. The invention also relates to the process for the preparation of said compounds.

Although their preparation is generally difficult to implement, there is still a growing interest in crown ether compounds. Indeed, these compounds find an interest in many applications. Their use as complexing agent, phase transfer catalyst, detergent, surfactant, structurant for the synthesis of organogels or mineral solids or in various methods in analytical chemistry may be mentioned. Martin R. Johnson et al. described in Journal of Chemical Society. Perkin 1, 1980, 586, mono azo crown ethers. Later, he was described by Gong-Xin HE et al. 15 (Bull Chem Soc Jpn, 1990, 63, 401) crown monoazo and bis-mono aza crown ethers as well as their study in the complexation of cations. The Applicant in his research has discovered a new family of compounds of general formula (I) and (I '), comprising at least one aza-crown ether and a crown diaza-ether connected together by at least one carbon arm (or spacer) connecting the nitrogen atom of the aza-crown ether and one of the nitrogen atoms of the diaza-crown ether, the second nitrogen atom of the diaza-crown ether comprising a hydrogen atom or a carbon chain Where X, Y = either H or a carbon chain m = 1, 2, 3, 4, 5 or 6 n = 1, 2 or 3 p = 1.2 or 3 y = 5 to 30 z = 3,4,5,6,7,8,9 or 10.

DETAILED DESCRIPTION OF THE INVENTION The novel compounds of general formula (I) and (I ') comprise at least one crown azaether and one crown diaza-ether connected together by at least one carbon arm (also called spacer) connecting the atom of nitrogen of the aza-crown ether and one of the nitrogen atoms of the diaza-crown ether, the second nitrogen atom of the diaza-crown ether comprising a hydrogen atom or a carbon chain, CI-13 I HN in which X, Y = indifferently H or a carbon chain m = 1, 2, 3, 4, 5 or 6 n = 1, 2 or 3 p = 1.2 or 3 y = 5 to 30 z = 3.4, 5,6,7,8,9 or 10.

The substituents X and Y may be independently selected from a hydrogen atom or a carbon chain. According to the invention, the carbon chain is advantageously an alkyl chain comprising 1 to 4 carbon atoms.

Advantageously according to the invention, the compounds of general formula (I) and (I ') have a structure such that: m = 3 or 4 n = 1 or 2 p = 2 y = 16 to 26 z = 3.4, 5 or 6. The compounds of general formulas (I) and (I ') according to the invention can be advantageously isolated in hydrochloride form, after treatment, for example with a solution of HCl in an apolar aprotic solvent such as diethyl ether. (Et20). Process for the preparation of the compounds of general formula (I) and (I ') The compounds of general formula (I) and (I') according to the invention are advantageously prepared according to a process comprising the following steps: a1) a coupling step wherein a compound of general formula (II) and a compound of general formula (III) are contacted under suitable coupling reaction conditions to produce a compound of general formula (IV) IV b1) a deprotection step wherein the compound (IV) obtained in step a1) is brought into contact with a suitable reagent for removing the protecting group GP and thus producing a compound of the general formula (V) COOH II z-2 V cl) optionally, contacting the deprotected compound (V) with a compound of the general formula (VI) in the presence of a base in a polar solvent to produce a compound of the general formula (VII), YCH3 Y VI VII dl) a step discount in lac a compound of general formula (VII) resulting from step c1) or the compound of general formula (V) resulting from step 1) 1) is brought into contact with a reducing agent in order to obtain the compound of general formula (I) or (I ') according to the invention, X, Y, m, n, p, y and z of the compounds (I) or (I'), (II), (III), (IV) , (V), (VI), (VII) having the values given according to the invention, GP being an amine protecting group and Q being a leaving group.

In a variant of the process of the process according to the invention, the preparation of the compounds of general formula (I) or (I ') comprises the following steps: a2) a step in which the compound of general formula (III) is brought into contact with a compound of the general formula (VI) in the presence of a base in a polar solvent to produce a compound of the general formula (VIII), a deprotection step in which the product is brought into contact with of general formula (VIII) obtained in step a2) with a reagent adapted to remove the protective group GP and thus produce a compound of general formula (X) y HNP H3C Y \ NP GPX c2) a step in which the compound of general formula (X) or the compound of general formula (III) is contacted under suitable coupling reaction conditions in the presence of the compound of general formula (II) in order respectively to produce the compounds of general formula (VII ) or (IV), COOH z-. VII IV d2) a reduction step in which the compounds of general formula (VII) or (IV) are brought into contact with a reducing agent in order to obtain the compounds of general formula (I) or (I ') according to invention, the compounds of general formula (IV) being previously subjected to a deprotection step in which they are brought into contact with a reagent adapted to remove the protective group GP in order to obtain the compound of general formula (V), VX , Y, m, n, p, y and z of compounds (I) or (I '), (II), (III), (IV), (V), (VI), (VII) having the 10 values data according to the invention, GP being an amine protecting group and Q being a leaving group. Advantageously according to the invention, the protective group GP is chosen from the group comprising the carboxybenzyloxy (Cbz), p-methoxybenzyl cabonyl (Moz), tert-butyloxycarbonyl (Boc), acetyl (Ac) and benzoyl (Bz) protecting groups. , benzyl (Bn) or p-methoxybenzyl (PMB). Advantageously according to the invention, the leaving group Q may be any leaving group known to those skilled in the art. Advantageously, the leaving group Q is selected from the group consisting of halogens, alkylsulfonates, perfluoroalkylsulphonates, arylsulphonates, preferably Q is a halogen and more preferably Q is a bromine atom. Step of deprotection According to the process of the invention, the deprotection steps 131), b2) of the protective group as well as the step of prior deprotection of the compound of general formula (V) carried out before step d2) are advantageously carried out. implemented under standard deprotection conditions known to those skilled in the art as a function of the protecting group GP to be deprotected. Preferably, the deprotection of the protective group GP is carried out in an acid medium in the presence of acids such as HCl, CF 3 COOH, H 2 O 4, p-toluenesulphonic acid (TsOH), in an aprotic solvent such as an ether or an ester, preferably at a temperature between 0 and 100 ° C for a period of between 1 and 24 hours. Preferably, the solvent used is ethyl ether. Coupling step According to the method of the invention, the coupling reaction carried out in steps a1) and c2) is advantageously carried out under standard synthesis conditions known to those skilled in the art allowing the formation of a link amide between a carboxylic acid function and an amine. Advantageously, the coupling reaction according to the invention is carried out using at least one coupling agent chosen from dicyclohexylcarbodimide (DCC), 1-ethyl-3 (3-dimethylaminopropyl) carbodimide. (EDC), diisopropylcarbodiimide (DIC), and imethylaminopyridine (DMAP), 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-aza-benzotriazole (HOAt), hexafluorophosphate (2H), - (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyluronium (HBTU), (2- (7-aza-1H-benzotriazol-1-yl) -1,1,3 hexafluorophosphate , 3-tetramethyluronium (HATU) and benzotriazol-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (PyBOP), in an aprotic solvent such as dichloromethane or chloroform, at a temperature between 0 and 100 ° C for a period of between 1 and 24 hours, the coupling agent is advantageously dicyclohexylcarbodiimide (DCC).

Grafting step of a carbon chain on the second nitrogen of the diaza-crown ether According to the invention, the compounds of general formula (I) have a carbon chain grafted on the second nitrogen atom of the diaza-crown ether. Said carbon chain corresponds to the carbon chain of the compound of general formula (VI): CH 3 Y Thus, according to the preparation method of the invention, steps c1) and a2) of grafting said carbon chain of the compound of general formula ( VI) compounds of general formula (V) or (III) according to the preparation variants, are produced under the conventional conditions known to those skilled in the art for grafting a carbon chain on a secondary amine such as in the compounds of general formula (V) and (III). Advantageously, the steps c1) and a2) are carried out in the presence of a base such as an alkaline carbonate, preferentially Na2CO3, in a polar aprotic solvent such as a nitrile and more advantageously in Et3CN, at a temperature of between 80 and 150 ° C, preferably between 90 and 120 ° C for a period of between 1 and 24 hours. Stage of reduction of the ketones of the carbon arm.

The preparation method according to the invention leads to the formation of intermediate compounds of general formulas (IV), (V) or (VII), IV IV VII According to the preparation method of the invention, steps d1) and d2 ) are carried out in the presence of an amide reducing agent such as a hydride and more particularly with LiAlH 4 in an aprotic solvent such as an ether and more particularly in tetrahydrofuran (THF), at a temperature between 0 and 100 ° C for a period of between 1 and 24 hours. The intermediate compounds of the general formulas (V) or (VII) can be advantageously isolated in hydrochloride form after treatment, for example with a solution of HCl in an aprotic solvent such as diethyl ether (Et20). Other details and features of the invention will appear more clearly in the description of the two variants of the preparation method according to the invention illustrated in schemes A and B for the compound la in which X = Y = H, m = 3 , n = 1, p = 2, z = 4, y = 21. These embodiments given for the compound are it by way of example, and do not have any limiting character. This illustration of the method of the invention does not include all the components necessary for its implementation. Only the elements necessary for the understanding of the invention are represented therein, the person skilled in the art being able to complete this representation to implement the invention. According to a variant of the process of the invention, compound Ia is obtained according to scheme A. 4 - [(1-aza- (15-ether-crown-5) - 1-yl) -4-oxolbutyric acid (Compound 1) is reacted with tert-butyl 1,7-diaza- (15-ether-crown-5) -1-carboxylate (Compound 2) under coupling conditions in the presence of dicyclohexylcarbodiimide (DCC), triethylamine (NEt3) at room temperature in chloroform to obtain compound 3. Compound 3 is subsequently deprotected in a solution of HCl in anhydrous Et 2 O to obtain the 4 'compound directly which corresponds to the hydrochloride of the compound in free secondary amine form, here named compound 4: Advantageously, the compound 4 'is reacted with bromodocosane and Na 2 CO 3 in propionitrile at 100 ° C. to obtain the compound 5 which is subsequently reduced in the presence of LiAlH 4 in tetrahydrofuran (THF) to give compound 1a. ## STR3 ##, ## STR3 ##, ## STR2 ##, 25 ° C 2 HCl, Et 2 O / C 2 2 1-1, 45B, N a 2 CO 3 EtCN, 100 ° C LiAlH 4, THF 0, the 0 NJ b 22I According to another variant of the process of the invention, the compound la is obtained according to scheme B.

The tert-butyl 1,7-diaza- (15-ether-crown-5) -1-carboxylate (compound 2) is reacted with bromodocosane and Na 2 CO 3 in propionitrile at 100 ° C. to obtain the compound Compound 10 is then deprotected in a solution of HCl in Et2O to obtain compound 11. Compound 11 is then reacted with 4 - [(1-aza- (15-ether-crown-5) acid) 1-yl) -4-oxo] butyric acid (compound 1) under coupling conditions in the presence of dicyclohexylcarbodiimide (DCC), triethylamine (NEt3) at room temperature in chloroform to give the compound 5 which is subsequently reduced in the presence of LiAlH 4 in tetrahydrofuran (THF) to give the compound la (0 (0 HCl, Et 2 O -NH 2 JN-Boc C 22 F F EtCN, 100 ° C 45 Br, Na 2 CO 3 N-Boc C 22 H 4 L 5 C2245, N, N Et3N, DCC, CHCl3, 25 ° C L1AIH4, THF C0 0 Ni b221-145 Scheme B: preparation of the compound EXAMPLES Compound 1, acid 4-1 (1-aza- (15-crown-ether) -5) -1-v1) -4-oxo-butylene reaction medium containing aza-15-ether-crown-5 (1 g, 4.56 mmol, 1 eq.), succinic anhydride (0.91 g, 9.0 mmol, 2 eq.) and NEt 3 ( 2.5 mL, 18.0 mmol, 4 eq.) Is stirred at room temperature for 17 h under argon in 2 mL of acetonitrile. After evaporation of the solvent under reduced pressure, the solid is dissolved in 20 ml of CH 2 Cl 2 and then washed 3 times with 5 ml of a solution of 1 M HCl and 3 times with 5 ml of a 20% aqueous NaCl solution. The different aqueous phases are extracted twice with 10 ml of CH 2 Cl 2 because the product 1 has a relatively high affinity for water due to the large number of hetero atoms it contains. After combining the organic phases and evaporation of the solvent, 1 is obtained in the form of a semi-solid yellowish resin (1.3 g, 4.0 mmol) in a yield of 89%. 1H NMR 1H (δ, J): (CDCl3, 400MHz, 295K): 2.71 (m, 4H: COCH2CH2CON); 3.58 (m, 12H: CH 2 O); 3.64 (m, 6H: 2H CH 2 O + 4H CH 2 N); 3.83 (t, JCH 2 O = 6.0 Hz, 2H: CH 2 O). 13 C NMR (δ): (CDCl3, 100 MHz, 295K): 28.0 (1C: CH2COOH); 29.8 (1C, CH2CON); 49.79, 50.5 (2C, CH2N crown ether); 69.2, 69.4, 70.0, 70.3, 70.5, 71.5 (8C, CH 2 O crown ether); 172.7 (1C: CONR2), 176.2 (1C: COOH). IR (pure): ν (crril): 3300-2200, 1784, 1730, 1642, 1420, 1355, 1115, 731 Compound 2, 1,7-diaza- (15-ether-crown-5) -1-carboxylate tert-butyl The reaction medium containing 1,7-diaza-15-ether-crown-5 (1.0 g, 4.6 mmol, 1 eq.), and di-tert-butyl dicarbonate (1.0 g. g, 4.6 mmol, 1 eq.) is stirred at room temperature for 16 h in 15 ml of acetonitrile. After evaporation of the solvent under reduced pressure, the mixture obtained is purified by column chromatography with eluent acetone / NEt3 (95/5). The mono-protected compound elutes with a frontal ratio of 0.25 after the di-protected compound, the starting diamine remaining trapped in the silica, it is therefore difficult to recover. After evaporation of the eluent, the carbamate 2 is obtained in the form of an orange oil (0.61 g, 1.9 mmol) with a yield of 42%. (0 LN-Boc NH 2 NMR 1H (δ, J): (CDCl 3, 400 MHz, 295K): 1.32 (s, 9H, t-Bu); 2.5 (broad s, 1H, NH); 2.66 (m, 4H: CH2NH) 3.33 (m, 4H: CH2NBOC) 3.45 (m, 12H: CH2O) 13C NMR (δ): (CDCl3, 100 MHz, 295K): 28.3 (3C: t-Bu CH3); , 48.7, 48.9, 49.1, 49.5, 49.9 (4C, CH2N), 68.7, 68.9, 69.7, 69.8, 70.0, 70.3, 70.6, 70.8 (6C, CH2O), 79.5 (1C: Cquat of t-Bu), 155.5 ( 1C: NC00) IR (neat): v (cm-1): 1690, 1459, 1405, 1365, 1288, 1235, 1112, 77325 Compound 3, 7-1 (1-aza- (15-ether-crown) 5) tert-butyl -1- (1,4-dioxo-but-4-yl) -1,7-diaza (15-ether-crown-5) -1-carboxymate The reaction medium containing 1-acid (100 mg, 0.31 mmol, 1 eq) and the DCC (64 mg, 0.31 mmol, 1 eq) is stirred at room temperature for 1 h in 0.4 ml of chloroform. carbamate 2 (150 mg, 0.47 mmol, 1.5 eq) and NEt 3 (128 μl, 0.92 mmol, 3 eq) The mixture is stirred at room temperature for 17 h 50 μL is added to the mixture of distilled water and one ag It is vigorously kept for 4 hours. This step makes it possible to hydrolyze DCC to 1,3-dicyclohexylurea. The solution is then coevaporated with toluene under reduced pressure. The mixture is then extracted 3 times with 1 ml of anhydrous toluene. 234 mg of products are obtained in the organic phase, while 60 mg of urea are collected in the precipitate which appears. The organic phase mixture is then separated by column chromatography in a pure acetone (50 ml) and then acetone / NEt 3 (95/5) eluent, the desired compound having a 0.62 front ratio. After evaporation of the eluent, the compound 3 is obtained in the form of an orange oil (75 mg, 0.12 mmol) with a yield of 39%. (-0) O / OtBu 3 1H NMR (δ, J): (CDCl3, 400 MHz, 295K): 1.45 (s, 9H, t-Bu); 2.68 (m, 4H, NCOCH 2); 3.66 (m, 40H: CH 2 N + CH 2). 13 C NMR (δ): (CDCl3, 100 MHz, 295K): 28.3 (3C: t-Bu CH3); 28.5, 29.1 (2C: NCOCH2); 48.0, 48.2, 48.7, 49.3, 49.5, 50.2 (6C: CH2N); 68.6, 69.0, 69.3, 69.4, 69.5, 70.0, 70.1, 70.4, 70.5, 70.6, 70.9, 71.3 (14C, CH2O); 79.5 (1C: Cquat of t-Bu); 155.5 (1C: NC00), 172.5, 172.7 (2C: NCOCH2).

Compound 4 ', f (1-aza- (15-ether-crown-5) -1- (1,4-dioxo-but-4- V01-1,7-diaza) (15-ether-crown) hydrochloride 5) The reaction medium containing compound 3 (290 mg, 0.47 mmol, 1 eq.) And a solution of 2.5 M HCl in anhydrous Et 2 O (1 ml, 2.5 mmol of HCl, 5 eq. ) is stirred at room temperature for 18 h After evaporation of the solvent, the hydrochloride 4 'is obtained in the form of a yellowish paste (260 mg, 0.47 mmol) in a yield of 100%. O, J): (CDCl3, 400 MHz, 295K): 2.65 (m, 4H, NCOCH2), 3.26 (m, 6H: 3 GH2N), 3.59 (m, 34H, 3 CH2N + 14CH2O), 9.13 (s, 1H: NH 2 Cl); 9.30 (s, 1H: NH 2 Cl) 13C NMR (δ): (CDCl 3, 100MHz, 295K): 28.0, 28.3 (2C: CH 2 CON), 47.5, 47.8, 48.4, 49.0, 49.1, 49.6, 50.0 (4C: CH2NCO); 65.6, 65.9 (2C: CH2NH2Cl); 67.9, 68.6, 69.3, 69.7, 70.0, 70.5, 71.0 (14C, CH2O); 172.2, 172.7 (2C: NCOCH2). IR (pure): v (cm-1): 3100-2500, 1636, 1579, 1518, 1447, 1355, 1115, 74825 Compound 5, 7-1 (1-aza- (15-ether-crown-5) -1- (1) , 4-dioxo-but-4-yl) 1-1,7-diaza (15-ether-crown-5) -1-docosyl A solution of 4 'hydrochloride (245 mg, 0.44 mmol, 1 eq.) , bromodocosane (172 mg, 0.44 mmol, 1 eq.) and Na2CO3 (94 mg, 0.88 mmol, 2 eq.) is heated at 100 ° C for 22 h in 25 mL of propionitrile. After evaporation of the solvent under reduced pressure, a mixture of 882 mg of crude products is obtained which is resolved by column chromatography with an acetone / NEt 3 mixture (95/5) as eluent, the frontal ratio of compound 5 is 0.52. .

After evaporation of the eluent, the product is obtained as an orange-yellow oil (120 mg, 0.15 mmol) with a yield of 33%. Carbon chain numbered starting from the nitrogen of the heterocycle to which it is connected 1H NMR (δ, J): (CDCl3, 400 MHz, 295K): 0.88 (t, 3H, J (22.21) = 6, 8 Hz, CH3 (22)); 1.26 (broad s, 38H); 1.42 (m, 2H, CH 2 (2)); 2.46 (broad t, J (1, 2) = 7 Hz, 2H, NCH 2 (1)); 2.71 (m, 4H, NCOCH 2); 2.73 (m, 4H, NCH 2); 3.65 (m, 36H, 14 OCH 2 + 4 NCH 2). 13 C NMR (δ): (CDCl3, 100 MHz, 295K): 14.1 (C (22)); 22.7 (C (21)); 27.4 (C (3)); 28.4 (C (2)); 29.3, 29.6, 29.7, 30.9 (16C: C (4-19)); 31.9 (C (20)); 53.9, 54.4 (4NCH2); 56.8 (NC (1)); 69.0, 69.4, 69.6, 70.1, 70.3, 70.7, 71.5 (14C: OCH2); 172.4, 172.5 (2C: NCO). IR (neat): ν (crril): 1642, 1467, 1355, 1293, 1119, 720 HRMS: calcd. For C46H89N3O9 + H: 828.66716, found: 828.66759 calcd for C46H89N3O9 + Na: 850.64910, found: 850.64939 Compound la, 7-1 (1-aza- (15-ether-crown-5) -1- (but-4-yl) 1-1,7-diaza- (15-ether-5-crown) - 1-docosvl The reaction medium containing compound 5 (563 mg, 0.68 mmol, 1 eq.) And LiAlH 4 (100 mg, 2.6 mmol, 4 eq.) Is stirred at 25 ° C. for 18 h in 18 hours. Then, the reaction mixture is added with a portion of 1.5 g of (Na 2 SO 4 · 10H 2 O) and then with 0.5 ml of a 1M solution of NaOH. ml of AcOEt (vigorous stirring for 20 minutes) then centrifuged This operation is repeated 3 times in order to extract the whole product After evaporation of the AcOEt, the oil obtained is dissolved in Et20 and then isolated under form of its crystalline trihydrochloride salt by addition of a solution of 5M HCl in Et 2 O. 431 mg of t Hydrochloride is obtained at a yield of 70%. (Ho C) CI -) HCI 0 HCIN N '\ I-C221-145 la, 3HCI carbon chain numbered starting from the nitrogen of the heterocycle to which it is connected.

1 H NMR (δ, J): (CDCl3, 300 MHz, 295K): 0.81 (t, 3H, J (22.21) = 6.8 Hz, CH3 (22)); 1.26 (broad s, 40H); 1.75 (m, 4H, CH 2 in [3 of the nitrogen]; 3.2-4.6 (solid, 46H, 18 NCH2 + 28 OCH2, 9.09 (s, 1H: NHCI), 9.79 (s, 1H: NHCI), 10.34 (s, 1H: NHCI) 13C NMR (δ): (CDCl3, 75) MHz, 295K): 13.1 (C (22)), 21.7 (C (21)), 25.8 (C (3)), 28.1, 28.3, 28.5, 28.6, 28.7, (19C: C (2), C (4); - 19), C at p of nitrogen; 30.9 (C (20)), 46.5, 46.6, 46.8, 51.3, 52.1, 52.5, 53.2, 53.6 (9C: NCH2), 63.0, 63.2, 64.1, 64.6, 64.7, 65.1, 68.2, 68.6, 68.8, 69.4 (14C: OCH2) IR (neat): v (cm-1): 3390, 1640, 1467, 1125, 1100, 721 HRMS: calcd for C46H93N3O7 + H: 800.70863 found: 800.70926 calcd for C461-193N3O7 + Na: 822.69057, found: 822.69157

Claims (16)

REVENDICATIONS1. Bis-aza-ether crowns corresponding to the general formula (I) or (I ') comprising at least one aza-crown ether and a diaza-crown ether connected together by at least one carbon arm connecting the nitrogen atom of the aza-ether crown and one of the nitrogen atoms of the diaza-crown ether, the second nitrogen atom of the diaza-crown ether comprising a hydrogen atom or a carbon chain, CH315in which X, Y = indifferently H or a carbon chain m = 1, 2, 3, 4, 5 or 6 n = 1, 2 or 3 p = 1,2 or 3 y = 5 to 30 z = 3,4,5,6,7,8,9 or 10 2. Bis-aza-ether crowns according to claim 1 wherein m = 3 or 4 n = 1 or 2 p = 2 y = 16 to 26 z = 3, 4, 5 or 6 3. Bis-aza-ether crowns according to claim 1 or 2 wherein X, Y represents indifferently a carbon chain comprising 1 to 4 carbon atoms. 4. Bis-aza-ether crowns according to claims 1 to 3 in hydrochloride form. 25 5. Bis-aza-ether rings of formula of formulas (IV), (V) or (VII) VII IV VII wherein X, Y, m, n, p, y and z have the values given in claim 1 and GP being an amine protecting group. 6. Bis-aza-ether crown (V) or (VII) according to claim 5 in hydrochloride form. 7. Process for the preparation of a compound of general formula (I) or (I ') according to claim 1, comprising the following steps: a1) a coupling step in which a coupling reaction is brought into contact under suitable coupling conditions; compound of the general formula (II) and a compound of the general formula (III) to produce a compound of the general formula (IV) H 15 (Of ---) ## STR2 ## bl) a deprotection step in which the compound (IV) obtained in step a1) is brought into contact with a reagent adapted to eliminate the protective group GP and thus produce a compound of general formula (V) V cl) a step optional for bringing the compound (V) deprotected in step b1) into contact with a compound of general formula (VI) in the presence of a base in a polar solvent in order to produce a compound of general formula (VII), orsj N ......-- GP 0 VIVII dl) a reduction step in which we put in contact with a reducing agent, the compound of general formula (VII) resulting from stage c1) or the compound of general formula (V) resulting from stage b1) in order to obtain the compound of general formula (I) or ( I ') according to claim 1, X, Y, m, n, p, y and z of the compounds (I) or (I'), (II), (III), (IV), (V), (VI ), (VII) having the values given in claim 1, GP being an amine protecting group and Q being a leaving group. 8. Process for the preparation of a compound of the general formula (I) or (I ') according to claim 1 comprising the following steps: a2) a step of contacting the compound of the general formula (III) with a compound of the general formula (VI) in the presence of a base in a polar solvent to produce a compound of the general formula (VIII), a deprotection step in which is brought into contact with the product of general formula (VIII) obtained in step a2) with a reagent adapted to remove the protective group GP and thus produce a compound of general formula (X) X c2) a coupling step in which the compound of general formula (X) or the compound of general formula (III) is contacted under suitable coupling reaction conditions in the presence of the compound of general formula (II) in order respectively to produce the compounds of general formula (VII ) or (IV), VII COOH 11 N GP or -s / IV d2) a reduction step in which the compounds of general formula (VII) or (IV) are brought into contact with a reducing agent in order to obtain the compounds of general formula (I) or (I ') according to claim 1, the compounds of general formula (IV) being previously subjected to a deprotection step in which they are brought into contact with a reagent adapted to remove the protective group GP in order to obtain the compound of the general formula (V), VX, Y, m, n, p, y and z of the compounds (I) or (I '), (II), (III), (IV), (V), (VI), (VII) having the values given in claim 1, GP being an amine protecting group and Q being a leaving group. 9. Process according to claims 7 and 8 wherein the protective group GP is selected from the group comprising the protecting groups carboxybenzyloxy (Cbz), p-methoxybenzyl cabonyl (Moz), tert-butyloxycarbonyl (Boc), acetyl (Ac), Benzoyl (Bz), benzyl (Bn) or p-methoxybenzyl (PMB). 10. The method of claims 7 to 9 wherein the leaving group Q is selected from the group consisting of halogens, alkyl sulfonates, perfluoroalkyl sulfonates, aryl sulfonates. 11. Process according to claims 7 to 10 wherein steps 1) 1), b2) and the preliminary deprotection of the compound of general formula (V) carried out before step d2) is carried out in an acid medium in the presence of acids such as HCl, CF 3 COOH, H 2 SO 4, p-toluenesulphonic acid (T 50 H), in an aprotic solvent such as an ether or an ester, at a temperature between 0 and 100 ° C. for a duration of between 1 and 24 hours. The process of claim 11 wherein the solvent is ethyl ether. 13. A process according to claims 7 to 12 wherein the coupling reaction of steps a1 and c2) is carried out using at least one coupling agent selected from dicyclohexylcarbodiimide (DCC), 1-ethyl-3 ( 3-dimethylaminopropyl) carbodiimide (EDC), diisopropylcarbodiimide (DIC), and dimethylaminopyridine (DMAP), 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-aza-benzotriazole (HOAt), (2- (1H-benzotriazol-1-yl) -1,3,3,3-tetramethyluronium hexafluorophosphate (HBTU), (2- (7-aza-1H-benzotriazol-1-yl) hexafluorophosphate 1,1,3,3-tetramethyluronium (HATU) and benzotriazol-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (PyBOP), in an aprotic solvent such as dichloromethane or chloroform, at a temperature between 0 and 100 ° C for a period of between 1 and 24 hours. The method of claim 13 wherein the coupling agent is dicyclohexylcarbodiimide (DCC). 15. The process as claimed in claim 7, in which steps c1) and a2) are carried out in the presence of a base such as an alkaline carbonate in a polar aprotic solvent such as a nitrile at a temperature of between 80 and 150. ° C for a period between 1 and 24 hours. 16. The process as claimed in claim 7, in which the steps d1) and d2) are carried out in the presence of a functional reducing agent such as a hydride in an aprotic solvent such as an ether at a temperature between 0 and 100 ° C for a period of between 1 and 24 hours. 15 20 25