Process for the high-yield preparation of P-(R)calix[9-20]arenes

Abstract

A process for the high-yield preparation of p-(R)calix[9-20]arenes.

Claims

1. A process for preparing: a large p-(R)calixarene selected from the group consisting of a p-(R)calix[9]arene, a p-(R)calix[10]arene, a p-(R)calix[11]arene, a p-(R)calix[12]arene, a p-(R)calix[13]arene, a p-(R)calix[14]arene, a p-(R)calix[15]arene, a p-(R)calix[16]arene, a p-(R)calix[17]arene, a p-(R)calix[18]arene, a p-(R)calix[19]arene, and a p-(R)calix[20]arene, or a mixture of at least two of said large p-(R)calixarenes in which said at least two large p-(R)calixarenes are present in said mixture each at a level of at least 5 mol. %, said process comprising: bringing at least one base selected from the group consisting of barium hydroxide, rubidium hydroxide, lithium hydroxide, caesium hydroxide, potassium hydroxide and sodium hydroxide, into contact with at least one phenol substituted in position 4 of the following formula (I): ##STR00005## in which R is selected from: a benzyl group optionally substituted in the ortho and/or para and/or meta position with one or more substituents selected from a halogen, SR′ and OR′, R′ representing a linear or branched C.sub.1-C.sub.20 alkyl chain, a C.sub.3 to C.sub.20 cycloalkyl group, NR.sub.aR.sub.b, PR.sub.aR.sub.b, P(O)R.sub.aR.sub.b, P(O)OR.sub.aOR.sub.b, R.sub.a and R.sub.b representing, independently of one another, a linear or branched C.sub.1-C.sub.20 alkyl, a linear or branched C.sub.1-C.sub.20 alkyl group, with the exclusion of the t-butyl group, a benzyloxy group optionally substituted in the ortho and/or para and/or meta position with one or more substituents selected from a halogen, SR′ and OR′, R′ representing a linear or branched C.sub.1-C.sub.20 alkyl chain, a C.sub.3 to C.sub.20 cycloalkyl group, NR.sub.aR.sub.b, PR.sub.aR.sub.b, P(O)R.sub.aR.sub.b, P(O)OR.sub.aOR.sub.b, R.sub.a and R.sub.b representing, independently of one another, a linear or branched C.sub.1-C.sub.20 alkyl, a linear or branched C.sub.1-C.sub.20 alkyloxy group, a linear or branched 1 to 10 O-PEG group, the —OH end group of which is alkylated with a linear or branched C.sub.1-C.sub.20 alkyl, a benzyl thioether group —S—CH.sub.2-Ph optionally substituted in the ortho and/or para and/or meta position with one or more substituents selected from a halogen, SR′ and OR′, NR.sub.aR.sub.b, PR.sub.aR.sub.b, P(O)R.sub.aR.sub.b, P(O)OR.sub.aOR.sub.b, R.sub.a and R.sub.b representing, independently of one another, a linear or branched C.sub.1-C.sub.20 alkyl, a linear or branched C.sub.1-C.sub.20 alkyl thioether group, of formula —S—(C.sub.1-C.sub.20-alkyl), an —NR.sub.aR.sub.b group, R.sub.a and R.sub.b representing, independently of one another, a linear or branched C.sub.1-C.sub.20 alkyl, and a dibenzylamine group of formula —N(benzyl).sub.2, in which the two benzyl groups are, independently of one another, optionally substituted in the ortho and/or para and/or meta position with one or more substituents selected from a halogen, SR′ and OR′, R′ representing a linear or branched C.sub.1-C.sub.20 alkyl chain, a C.sub.3 to C.sub.20 cycloalkyl group, NR.sub.aR.sub.b, PR.sub.aR.sub.b, P(O)R.sub.aR.sub.b, P(O)OR.sub.aOR.sub.b, R.sub.a and R.sub.b representing, independently of one another, a linear or branched C.sub.1-C.sub.20 alkyl, and a source of aqueous formaldehyde, in the absence of an organic solvent, thus constituting an initial reaction medium, said base being at a total concentration comprised from approximately 0.01 to 1 equivalent, with respect to said at least one phenol substituted in position 4 of formula (I), said initial reaction medium being heated to a temperature comprised from 100 to 165° C., in order to obtain a heated reaction medium; optionally, after said heating, additional heat treating of said heated reaction medium, in the presence of heat transfer means, in order to obtain a mixture (b), comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, said mixture (b) comprising in addition a mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20; and after said heating and optional additional heat treating, purifying said mixture (b), so as to remove said mixture (c) of giant p-(R)calixarenes, and to obtain said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes.

2. The process according to claim 1, for the preparation of: a large p-(R)calixarene selected from the group consisting of a p-(R)calix[9]arene, a p-(R)calix[10]arene, a p-(R)calix[11]arene, and a p-(R)calix[12]arene, or a mixture of at least two of said large p-(R)calixarenes in which said at least two large p-(R)calixarenes are present in said mixture each at a level of at least 5 mol. %.

3. The process according to claim 1, for the preparation of: a large p-(R.sub.1-oxy)calixarene selected from the group consisting of a p-(R.sub.1-oxy)calix[9]arene, a p-(R.sub.1-oxy)calix[10]arene, a p-(R.sub.1-oxy)calix[11]arene, a p-(R.sub.1-oxy)calix[12]arene, a p-(R.sub.1-oxy)calix[13]arene, a p-(R.sub.1-oxy)calix[14]arene, a p-(R.sub.1-oxy)calix[15]arene, a p-(R.sub.1-oxy)calix[16]arene, a p-(R.sub.1-oxy)calix[17]arene, a p-(R.sub.1-oxy)calix[18]arene, a p-(R.sub.1-oxy)calix[19]arene, and a p-(R.sub.1-oxy)calix[20]arene, or a mixture of at least two of said large p-(R.sub.1-oxy)calixarenes in which said at least two large p-(R.sub.1-oxy)calixarenes are present in said mixture each at a level of at least 5 mol. %, said process comprising: bringing at least one base selected from the group consisting of barium hydroxide, rubidium hydroxide, lithium hydroxide, caesium hydroxide, potassium hydroxide and sodium hydroxide, into contact with at least one phenol substituted in position 4 of the following formula (Ia): ##STR00006## in which R.sub.1 is selected from: a benzyl group optionally substituted in the ortho and/or para and/or meta position with one or more substituents selected from a halogen, SR′ and OR′, R′ representing a linear or branched C.sub.1-C.sub.20 alkyl chain, a C.sub.3 to C.sub.20 cycloalkyl group, NR.sub.aR.sub.b, PR.sub.aR.sub.b, P(O)R.sub.aR.sub.b, P(O)OR.sub.aOR.sub.b, R.sub.a and R.sub.b representing, independently of one another, a linear or branched C.sub.1-C.sub.20 alkyl, a linear or branched C.sub.1-C.sub.20 alkyl group, and a linear or branched PEG 1 to 10, the —OH end group of which is alkylated with a linear or branched C.sub.1-C.sub.20 alkyl, and a source of aqueous formaldehyde, in the absence of an organic solvent, thus constituting an initial reaction medium, said base being at a total concentration comprised from approximately 0.01 to 1 equivalent, with respect to said at least one phenol substituted in position 4 of formula (I), said initial reaction medium being heated to a temperature comprised from 100 to 165° C., in order to obtain a heated reaction medium; optionally, after said heating, additional heat treating of said heated reaction medium, in the presence of heat transfer means, in order to obtain a mixture (b), comprising said large p-(R.sub.1-oxy)calixarene or said mixture (a) of at least two of said large p-(R.sub.1-oxy)calixarenes, said mixture (b) comprising in addition a mixture (c) of giant p-(R.sub.1-oxy)calixarenes, the size of which is greater than 20; and after said heating and optional additional heat treating, purifying said mixture (b), so as to remove said mixture (c) of giant p-(R.sub.1-oxy)calixarenes, and to obtain said large p-(R.sub.1-oxy)calixarene or said mixture (a) of at least two of said large p-(R.sub.1-oxy)calixarenes, devoid of said mixture (c) of giant p-(R.sub.1-oxy)calixarenes.

4. The process according to claim 1, for preparing: a large p-(R.sub.1-oxy)calixarene selected from the group consisting of a p-(R.sub.1-oxy)calix[9]arene, a p-(R.sub.1-oxy)calix[10]arene, a p-(R.sub.1-oxy)calix[11]arene, and a p-(R.sub.1-oxy)calix[12]arene, or a mixture of at least two of said large p-(R.sub.1-oxy)calixarenes in which said at least two large p-(R.sub.1-oxy)calixarenes are present in said mixture each at a level of at least 5 mol. %.

5. The process according to claim 1, in which water present in the initial reaction medium, as well as that produced during the reaction, is removed from said reaction medium during said heating and a solid precursor in the form of optionally isolated hard brittle resin is obtained, wherein: said solid precursor in the form of hard brittle resin is isolated from the of reaction medium and not subjected to said additional heat treating, or said solid precursor in the form of hard brittle resin, contained in said reaction medium, is placed in the presence of heat transfer means in the form of an oven, or of a heated liquid in which said solid precursor in the form of hard brittle resin is very slightly soluble or totally insoluble in toluene, xylene, a linear or branched alkane with a boiling point greater than 50° C., or a silicone oil, and is subjected to said additional heat treating.

6. The process according to claim 1, comprising the steps of: a. bringing at least one base, selected from the group consisting of barium hydroxide, rubidium hydroxide, lithium hydroxide, caesium hydroxide, potassium hydroxide and sodium hydroxide, into contact with at least one phenol substituted in position 4 of formula (I), with aqueous formaldehyde, in order to constitute an initial reaction medium and heating of said initial reaction medium for a time comprised from 20 minutes to 2 hours, while optionally removing the water present in the initial reaction medium as well as that formed, b. continuing the heating of said reaction medium for 1 to 3 hours, while optionally removing the water present in the reaction medium as well as that formed, in order to obtain a reaction medium containing a solid precursor, in the form of hard brittle resin, c. heating of said reaction medium or said solid precursor using heat transmission means in the form of an oven, for 3 to 24 hours, or adding to said reaction medium or to said solid precursor in the form of hard brittle resin, a liquid in which said solid precursor in the form of hard brittle resin is very slightly soluble or totally insoluble in toluene, xylene, a linear or branched alkane with a boiling point greater than 50° C., or a silicone oil, in order to obtain a reaction medium containing a solid in the form of hard brittle resin, and heating of said reaction medium containing a solid in the form of hard brittle resin, for 3 to 24 hours, with or without stirring, in order to obtain a mixture (b), comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, said mixture (b) comprising in addition a mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20, d. optionally, after neutralizing the base, at least one washing of said mixture (b) with a polar solvent, in order to obtain said mixture (b) in neutralized form, e. purifying said mixture (b), optionally neutralized, so as to remove said mixture (c) of giant p-(R)calixarenes, and to obtain said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, f. optionally, purifying mixture (a) using GPC, by separating different fractions depending on their elution time, in order to obtain said large p-(R)calixarene.

7. The process according to claim 1, in which the water present in the initial reaction medium, as well as that produced during the reaction, are retained in the reaction medium during said heating and a solid precursor in the form of optionally isolated precipitate is obtained, wherein said solid precursor in the form of precipitate is isolated from the aforesaid reaction medium and not subjected to additional heat treatment.

8. The process according to claim 7, in which the water present in the initial reaction medium, as well as that produced during the reaction, are retained in said reaction medium during said heating and a solid precursor in the form of optionally isolated precipitate is obtained, wherein said solid precursor in the form of precipitate is isolated from the aforesaid reaction medium and not subjected to additional heat treatment.

9. The process according to claim 1, in which said purifying said mixture (b) comprises recrystallizing of said mixture (b) in order to obtain at the end of the recrystallizing a precipitate and a filtrate, said filtrate comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and the precipitate comprising said mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20.

10. The process according to claim 1, in which said purifying of said mixture (b) comprises a recrystallizing with two solvents of said mixture (b) in order to obtain, after adding the second solvent, a precipitate and a filtrate, said filtrate comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, and mixture (c) of giant p-(R)calixarenes, and the precipitate comprising mainly calix[8]arene.

11. The process according to claim 1, in which said purifying of said mixture (b) comprises the steps of: dissolving said mixture (b) in a minimum amount of a first solvent, hot, in order to obtain a hot solution of said mixture (b), adding a second solvent to the hot solution of said mixture (b), until a precipitate appears, and immediate filtration, in order to obtain a filtrate containing the large calixarenes and the giant calixarenes, after cooling of the filtrate obtained previously, filtration of said precipitate in order to obtain: a filtrate comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and the isolated precipitate, comprising said mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20.

12. The process according to claim 1, in which said purifying of said mixture (b) comprises the steps of: dissolving said mixture (b) in a minimum amount of a first solvent, hot, in order to obtain a hot solution of said mixture (b), adding a second solvent to the hot solution of said mixture (b), until a first precipitate appears, hot filtering of said first precipitate in order to obtain a filtrate, cooling of the filtrate in order to obtain the formation of a second precipitate, filtering of said second precipitate in order to obtain: a filtrate comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and the isolated precipitate, comprising said mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20.

13. The process according to claim 1, in which said purifying of said mixture (b) comprises the steps of: dissolving said mixture (b) in a minimum amount of DMSO, at a temperature comprised from approximately 80° C. to approximately 160° C., in order to obtain a hot solution of said mixture (b), adding a second, averagely polar solvent, in particular acetone, to the hot solution of said mixture (b), until a first precipitate appears, hot filtering of said first precipitate in order to obtain a filtrate, cooling of the filtrate to approximately 0° C. in order to obtain the formation of a second precipitate, filtering of said second precipitate in order to obtain: a filtrate comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and the isolated precipitate, comprising said mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20, concentrating said filtrate in order to obtain said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes.

14. The process according to claim 1, in which said purifying of said mixture (b) comprises the steps of: dissolving said mixture (b) in a minimum amount of DMSO, at a temperature comprised from approximately 80° C. to approximately 160° C., in order to obtain a hot solution of said mixture (b), adding a second, averagely polar solvent, in particular acetone, to the hot solution of said mixture (b), until a first precipitate appears, hot filtering of said first precipitate in order to obtain a filtrate, cooling of the filtrate to approximately 0° C. in order to obtain the formation of a second precipitate, filtering of said second precipitate in order to obtain: a filtrate comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and the isolated precipitate, comprising said mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20, concentrating of said filtrate in order to obtain a residue devoid of acetone, adding to said residue of a polar solvent, in order to obtain a solution of said residue in said polar solvent, cooling of said solution of said residue, in order to obtain a suspension, said suspension being filtered in order to obtain a filtrate, said filtrate being concentrated in order to obtain said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes.

15. The process according to claim 1, wherein water present in the initial reaction medium, as well as that produced during the reaction, is removed from said reaction medium during said heating and a solid precursor in the form of optionally isolated hard brittle resin is obtained, and said process comprises the steps of: bringing at least one base selected from the group consisting of barium hydroxide, rubidium hydroxide, lithium hydroxide, caesium hydroxide, potassium hydroxide and sodium hydroxide, into contact with at least one phenol substituted in position 4 of formula (I), with aqueous formaldehyde, in order to constitute an initial reaction medium, and heating of said initial reaction medium for a time comprised from 20 minutes to 2 hours, while optionally removing the water present in the initial reaction medium as well as that formed, continuing the heating of said reaction medium for 1 to 3 hours, while optionally removing the water present in the reaction medium as well as that formed, in order to obtain a reaction medium containing a solid precursor, in the form of hard brittle resin, optionally: heating of said reaction medium or said solid precursor using heat transmission means in the form of an oven, for 3 to 24 hours, adding to said reaction medium or to said solid precursor in the form of hard brittle resin, a liquid in which said solid precursor in the form of hard brittle resin is very slightly soluble or totally insoluble in toluene, xylene, a linear or branched alkane with a boiling point greater than 50° C., or a silicone oil, in order to obtain a reaction medium containing a solid in the form of hard brittle resin, and heating of said reaction medium containing a solid in the form of hard brittle resin, for 3 to 24 hours, with or without stirring, in order to obtain a mixture (b), comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, said mixture (b) comprising in addition a mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20, optionally, after neutralizing the base, at least one washing of said mixture (b) with a polar solvent, in order to obtain said mixture (b) in neutralized form, purifying said mixture (b), optionally neutralized, so as to remove said mixture (c) of giant p-(R)calixarenes, and to obtain said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and optionally purifying said mixture (a) using GPC, by separating different fractions depending on their elution time, in order to obtain said large p-(R)calixarene.

16. The process according to claim 1, wherein the water present in the initial reaction medium, as well as that produced during the reaction, are retained in the reaction medium during said heating and a solid precursor in the form of optionally isolated precipitate is obtained, and said process comprises the steps of: bringing at least one base, selected from the group consisting of barium hydroxide, rubidium hydroxide, lithium hydroxide, caesium hydroxide, potassium hydroxide and sodium hydroxide, into contact with at least one phenol substituted in position 4 of formula (I), with aqueous formaldehyde, in order to constitute an initial reaction medium and heating of said initial reaction medium for a time comprised from 20 minutes to 5 hours, without removing the water present in the initial reaction medium as well as that formed, in order to obtain a reaction medium containing a solid precursor, in the form of precipitate, optionally, adding to said reaction medium or to said solid precursor in the form of precipitate, a liquid in which said solid precursor in the form of precipitate is very slightly soluble or totally insoluble in toluene, xylene, a linear or branched alkane with a boiling point greater than 50° C., or a silicone oil, in order to obtain a reaction medium containing a solid in the form of precipitate, and heating of said reaction medium containing a solid in the form of precipitate, for 3 to 24 hours, with or without stirring, in order to obtain a mixture (b), comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, said mixture (b) comprising in addition a mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20, optionally, after neutralizing the base, at least one washing of said mixture (b) with a polar solvent, in order to obtain said mixture (b) in neutralized form, purifying said mixture (b), optionally neutralized, so as to remove said mixture (c) of giant p-(R)calixarenes, and to obtain said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and optionally, purifying mixture (a) using GPC, by separating different fractions depending on their elution time, in order to obtain said large p-(R)calixarene.

17. The process according to claim 16, comprising the steps of: bringing at least one base, selected from the group consisting of barium hydroxide, rubidium hydroxide, lithium hydroxide, caesium hydroxide, potassium hydroxide and sodium hydroxide, into contact with at least one phenol substituted in position 4 of formula (I), with aqueous formaldehyde, in order to constitute an initial reaction medium and heating of said initial reaction medium for a time comprised from 20 minutes to 5 hours, without removing the water present in the initial reaction medium as well as that formed, in order to obtain a reaction medium containing a solid precursor, in the form of precipitate, adding to said reaction medium or to said solid precursor in the form of precipitate, a liquid in which said solid precursor in the form of precipitate is very slightly soluble or totally insoluble in toluene, xylene, a linear or branched alkane with a boiling point greater than 50° C., or a silicone oil, in order to obtain a reaction medium containing a solid in the form of precipitate, and heating of said reaction medium containing a solid in the form of precipitate, for 3 to 24 hours, with or without stirring, in order to obtain a mixture (b), comprising said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, said mixture (b) comprising in addition a mixture (c) of giant p-(R)calixarenes, the size of which is greater than 20, optionally, after neutralizing the base, at least one washing of said mixture (b) with a polar solvent, in order to obtain said mixture (b) in neutralized form, purifying said mixture (b), optionally neutralized, so as to remove said mixture (c) of giant p-(R)calixarenes, and to obtain said large p-(R)calixarene or said mixture (a) of at least two of said large p-(R)calixarenes, devoid of said mixture (c) of giant p-(R)calixarenes, and optionally purifying of mixture (a) using GPC, by separating different fractions depending on their elution time, in order to obtain said large p-(R)calixarene.

Description

EXAMPLES

Example 1: Synthesis of Large Calixarenes, with Additional Heat Treatment in a Silicone Oil

(1) 104 g de p-(benzyloxy)phenol, 133 ml of formaldehyde in aqueous solution at 37%, and 36 ml of CsOH in aqueous solution at 50% are introduced into a 2-liter three-necked flask equipped with a mechanical stirrer.

(2) The resulting white suspension is brought to reflux under vigorous stirring.

(3) After approximately 30 minutes of reflux, a clear bright yellow solution is obtained.

(4) Vigorous argon flushing is introduced in the flask, in order to remove the water. The solution is thus progressively concentrated, until a hard brittle solid material is obtained.

(5) Then, 280 ml of silicone oil is added under argon and the heterogeneous reaction medium thus obtained is heated at 145° C. under argon flushing for 24 hours. No solubilization/evolution of solid is observed during this time.

(6) The silicone oil is removed by filtration. The yellow solid is then washed with 1 L of pentane under vigorous mechanical stirring. Then, it is dispersed in 1.5 l of MeOH under vigorous stirring. 40 ml of HCl at 37% is added to the fluid suspension thus obtained. The resulting precipitate is recovered by filtration, then dried in air.

(7) This precipitate is suspended in 1.5 l of acetonitrile under vigorous stirring overnight. The resulting fluid suspension is filtered, and the precipitate obtained recrystallized in a DMSO/acetone mixture (1/9) and filtered hot. After storing the filtrate in a refrigerator (1° C.) for 48 hours, 60 g of a precipitate constituted by giant calixarenes is obtained.

(8) The corresponding filtrate is concentrated in a rotary evaporator (removal of the acetone), and 20 ml of ethanol is added.

(9) The clear solution thus obtained is stored in a refrigerator (1° C.) for 48 hours. The suspension obtained is filtered.

(10) The corresponding filtrate is concentrated in a rotary evaporator and precipitated with 1 L of methanol.

(11) After filtration, 25 g of a mixture containing “large” calixarenes is thus obtained.

Example 2: Synthesis of Large Calixarenes, with Heat Treatment in Xylene

(12) 104 g de p-(benzyloxy)phenol, 140 ml of formaldehyde in aqueous solution at 37%, and 72 ml of CsOH in aqueous solution at 50% are introduced into a 2-liter three-necked flask equipped with a mechanical stirrer.

(13) The resulting white suspension is brought to reflux under vigorous stirring.

(14) After approximately 30 minutes of reflux, a clear bright yellow solution is obtained.

(15) Vigorous argon flushing is introduced in the flask, in order to remove the water. The solution is thus progressively concentrated, until a hard brittle solid material is obtained.

(16) Then, 200 ml of xylene is added under argon and the heterogeneous reaction medium thus obtained is brought to reflux at 145° C. without stirring for 5 hours.

(17) The yellow solid obtained is then neutralized with a mixture of 500 ml of THF and 50 ml of HCl at 37%, under vigorous stirring for one day.

(18) The suspension is evaporated to dryness, then washed with 1.2 L of MeOH under vigorous stirring overnight, then filtered. The precipitate obtained is suspended in 1.5 l of acetonitrile under vigorous stirring overnight. The resulting fluid suspension is filtered, and the precipitate obtained recrystallized in a DMSO/acetone mixture (175 ml/2 L) and filtered hot. After storing the filtrate in a refrigerator (1° C.) for 48 hours, 20 g of a precipitate constituted by giant calixarenes is obtained.

(19) The corresponding filtrate is concentrated in a rotary evaporator (removal of the acetone), and 20 ml of ethanol is added.

(20) The clear solution thus obtained is stored in a refrigerator (1° C.) for 48 hours. The suspension obtained is filtered.

(21) The corresponding filtrate is concentrated in a rotary evaporator and precipitated with 1 L of methanol.

(22) After filtration, 56 g of a mixture comprising “large” calixarenes is thus obtained.

Example 3: Synthesis of Large Calixarenes, with Heat Treatment in Xylene

(23) 104 g de p-(benzyloxy)phenol, 140 ml of formaldehyde in aqueous solution at 37%, and 50 ml of RbOH in aqueous solution at 50% are introduced into a 2-liter three-necked flask equipped with a mechanical stirrer.

(24) The resulting white suspension is brought to reflux under vigorous stirring.

(25) After approximately 30 minutes of reflux, a clear bright yellow solution is obtained.

(26) Vigorous argon flushing is introduced in the flask, in order to remove the water. The solution is thus progressively concentrated, until a hard brittle solid material is obtained.

(27) Then, 200 ml of xylene is added under argon and the heterogeneous reaction medium thus obtained is brought to reflux at 145° C. without stirring for 7 hours 30 minutes.

(28) The yellow solid obtained is then neutralized with a mixture of 500 ml of THF and 50 ml of HCl at 37%, under vigorous stirring for one day.

(29) The suspension obtained is evaporated to dryness, then washed with 2 L of MeOH under vigorous stirring overnight, then filtered. The precipitate obtained is suspended in 1 L of acetonitrile under vigorous stirring overnight. The resulting fluid suspension is filtered, and the precipitate obtained recrystallized in a DMSO/acetone mixture (200 ml/2 L) and filtered hot.

(30) After storing the filtrate in a refrigerator (1° C.) for 48 hours, 20 g of a precipitate constituted by giant calixarenes is obtained.

(31) The corresponding filtrate is concentrated in a rotary evaporator (removal of the acetone), and 20 ml of ethanol is added.

(32) The clear solution thus obtained is stored in a refrigerator (1° C.) for 24 hours. The suspension obtained is filtered.

(33) The corresponding filtrate is concentrated in a rotary evaporator and precipitated with 1 L of methanol.

(34) After filtration, 30 g of a mixture containing “large” calixarenes is thus obtained.

Example 4: Synthesis of a Star Polymer Derived from a Large Calixarene

(35) Synthesis of the Initiator

(36) ##STR00003##

(37) A large calixarene, here calix[12]arene (500 mg, 0.0002 mol), is introduced into a Schlenk tube. 5 mL of DMF and 1.5 mL of Et.sub.3N are then added under argon. The system is immersed in an ice bath. Then 300 μL of bromopropionyl bromide is introduced. The solution is stirred for 1 h. A precipitation is carried out from 50 mL of MeOH. Filtration under vacuum is carried out. The initiator is solubilized in a few milliliters of THF. Then a second precipitation is carried out with 50 mL of MeOH. Filtration under vacuum is carried out. The product is dried in a desiccator.

(38) Yield=60%.

(39) RMN.sup.1H (350 MHz, CDCl3) δ.sub.ppm: 7.1-7.6 (m, 60H, —OCH.sub.2—Ar), 6.8-6.4 (m, 24H, Ar), 5.1-4.7 (m, 24H, —OCH.sub.2—Ar—), 4-3.5 (m, 24H, —Ar(phenol)-CH.sub.2—), 3-1.5 (m, 24H, CH.sub.3—CH(COR)—Br), 2-1.5 (m, 36H, CH.sub.3—CH(COR)—Br).

(40) Synthesis of the Star Polymer by Atom Transfer Radical Polymerization (ATRP)

(41) ##STR00004##

(42) CuBr (25 mg, 0.00017 mol), bipyridine (80 mg, 0.00052 mol), the initiator obtained previously (60 mg, 0.00017 mol) and 2 mL of styrene are introduced into a Schlenk tube under argon. The reaction medium is degassed using 3 freeze-thaw cycles. The Schlenk tube is immersed in an oil bath heated at 100° C. for a given period of time. The mixture is solubilized in THF. The mixture is filtered on a column of basic Al.sub.2O.sub.3. The polymer is precipitated from MeOH

(43) $\left(\mathrm{with}a\mathrm{ratio}=\frac{\mathrm{THF}}{\mathrm{MeOH}}=10\right).$
The polymer is filtered under vacuum and rinsed with MeOH. The product is dried in a desiccator.

(44) Yield=50%.

(45) RMN.sup.1H (360 MHz, CDCl3) δ.sub.ppm: 7.1-7.6 (m, 5H, —OCH.sub.2—Ar), 7.2-6.9 (m, 5H, Ar.sub.styrene), 7.2-6.9 (m, 1H, —CH.sub.2—CH(Ar)—CH.sub.2—), 6.8-6.4 (m, 2H, Ar), 2.1-1.6 (m, 2H, —CH—CH.sub.2—CH—), 2.1-1.6 (m, 1H, HO.sub.2C—CH(CH.sub.3)—CH.sub.2—), 1.6-1.3 (m, 3H, CH.sub.3—CH—).

(46) The star polymers derived from the calix[12]arene exhibit specific “hard sphere”-type hydrodynamic behaviour, and therefore form well-defined nanoobjects in solution (THF), which are potentially useful for encapsulation and vectorization.