DD287256A5 - METHOD FOR PRODUCING CHIRAL WATER-SOLUBLE AMMONIUM ALKANSULFONSAEURES AND THEIR SALTS AND SULFOBETAINS - Google Patents

Abstract

The invention relates to a process for the preparation of chiral water-soluble ammonium alkane sulfonic acids and their salts and sulfobetaines, which can be used as auxiliaries for chiral chromatographic separation and for catalysts in aqueous solutions and in multiphase systems. According to the invention, chiral primary, secondary or tertiary amines, imides or amino acids are reacted with aliphatic sultones in protic or non-protic solvents at temperatures between 0 and 200 ° C. {chiral amine; sulfonate; Transition metal compound; Multiphase system; Sulton; sulfobetaine; aminoalkanesulfonic; chromatographic separation; Catalyst}

Description

Field of application of the invention

The invention relates to a process for the preparation of chiral water-soluble ammonium alkane sulfonic acids and their salts and sulfobetaines.

The compounds obtained can be used as chiral phase transfer catalysts - in conjunction with transition metals - in asymmetric catalysts application. Furthermore, they are also useful in chromatography, e.g. in HPLC or in column chromatography, as chiral reagents in the mobile phase for the separation of chiral substances or as specific detergents.

Characteristic of the known state of the art

A number of water-soluble ligands for catalytically active transition metal complexes whose hydrophilicity is based on the presence of hydroxyl, polyether, carboxy, ammonium or sulfonate groups are known (F. Joo, Z. Toth, J. Mol. Catal.8 369 1980]). Of these, the sulfonic group has acquired the greatest importance. In principle, the reaction of amines with alkene sultones has long been known (JH Helberger, G. Manecke, JR Heydon, J. Liebigs Ann. Chem. 565.22 [1949], I.Zeid, I. Ismail, J.üebigs Ann. Chem 667 [1974]).

Kunitake et al. used 1,3-propane sultone to display long-chain amphiphilic ammonium sulfobetaines as vesicle building blocks (Y. Okkata, S. Tanamachi, M. Nagai, T. Kunitake, J. Colloid Interface, p. 82, 401 [1981]). All previously known reactions of amines with sultones (see review article D.N. Roberts, D.L. Williams, Tetrahedron 43, 1027 [1987]) did not lead to chiral o. Links.

Object of the invention

It is the object of the invention to develop a simple process for the preparation of chiral aliphatic or araliphatic ammonium sulfonic acids and sulfobetaines, which can be used as novel water-soluble compounds in catalytically active systems or as auxiliaries for chiral chromatographic separations.

Explanation of the essence of the invention

The invention is based on the object by suitable starting compounds, the representation of sulfonated water-soluble chiral sulfobetaines, Ammoniumalkansulfonsäuren and their salts, which are present as aminosulfonates, to achieve a simple way.

This object is achieved by a process for the preparation of chiral water-soluble ammonium alkane sulfonic acids and their salts and solfobetaines of the general formula I,

R * ¹ R ² R ³ N ⁺ CHR ⁴ (CH ₂ ) _n SO ₃ "I

in the

r i = r 2 = r 3 is chiral alkyl, cycloalkyl, arylalkyl or arylalkenyl,

R * ¹ = R ² with the meaning given above and

R ^{3 is} hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, arylalkyl, arylalkenyl or substituted alkyl,

R * ¹ with the meaning given above or also carboxyalkyl,

R ² = R ^{3 is} hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, arylalkyl, arylalkenyl or substituted alkyl,

R * ¹ with the meaning given above or also carboxyalkyl and

R ² and R ^3, which may be the same or different, are hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, arylalkyl, arylalkenyl

or substituted alkyl and

R ^{4 is} hydrogen or alkyl

in that according to the invention a chiral, primary, secondary or tertiary amine, imide or an amino acid of the general formulas II, III and IV,

R * ¹ NH ₂ II

R * ¹ R ² NH III

Ff ¹ R ² R ³ N IV

in which R * ¹ , R ² and R ^{3 have} the abovementioned meanings,

with an aliphatic sultone of the general formula V, R ⁴

in the

R ^{4 has} the abovementioned meaning and

η is an integer equal to 2 or 3,

or is reacted with Tolylsulton at temperatures between 0 and 200 ⁰ C in a solvent.

The sultone used are in particular the aliphatic sultones 1,3-propane, 1,3-butane or 1,4-butane sultone and also tolylsultone.

The solvents used are protic and non-protic solvents or solvent mixtures, preferably ethers and aromatics, and also alcohols and ketones or mixtures thereof.

The reaction temperature should preferably be between 20 and 120 ° C.

As chiral amines are (-) - and (+) - a-phenylethylamine, R - (+) - bornylamine, N-methylglucamine, (-) - L-menthylamine, 1- [4-nitrophenyl] -1 (S), 3-dihydroxy-2 (S) -aminopropane ("L-base") and amino acids such as L-valine, L-leucine, (+) - L-proline, (-) - D-proline and L-valine-tert. Butylamide suitable.

Often, especially when non-polar solvents are used to dissolve the starting compounds, the reaction products from the reaction mixture precipitate almost reagent-free. They are made by washing with cold o.g.

Solvent or purified by column chromatography. Recrystallization from various solvents, preferably from alcohols or water-alcohol mixtures, leads to very pure products.

Sulfobetaines, ammonium alkanoic acids and salts thereof, which are prepared by the process according to the invention, can be used as water-soluble chiral compounds for asymmetric catalysis or in mobile phases of the chromatography of enantiomeric separations.

embodiments

example 1

606mg (5mmol) of (-) - a-phenylethylamine and 519μΙ (5mmol) of 1,4-butanesultone are added in 3ml abs. Toluen refluxed for five hours. After cooling, the solvent was decanted from the precipitate formed, the crystals washed several times with ether and dried in vacuo.

Yield: 812 mg (3.15 mmol, 63%) of C ₁₂ H ₁₉ O ₃ NS = 257.35

[α] "= -19.9 ° (с = 1.35, MeOH)

calc.%: C = 56.00 H = 7.44 N = 5.45 S = 12.46

%. C = 55.78 H = 7.65 N = 5.3 S = 12.0

Example 2

In a solution of 606 mg (5 mmol) of (H -) - a-phenylethylamine in 3 ml abs. Benzene was added to 610 mg (5 mmol) of propanesultone.

The reaction was stirred at room temperature and allowed to stand overnight. After about one hour, the formation of a precipitate is observed. The precipitate formed was filtered off with suction over a frit after 18 hours, washed three times with ether and dried over P ₂ O ₆ in a desiccator.

Yield: 1.05 g (4.32 mmol, 86%) C ₁₁ Hi ₇ O ₅ NS = 243.27

[α] ² , ² = + 20,1 ° (c = 1,13, H ₂ O)

calc.%: C = 54.22 H = 7.04 N = 5.76 S = 13.17

%. C = 54.46 H = 6.88 N = 6.0 S = 12.6

Example 3

2mmol (+ JR-bornylamine hydrochloride was dissolved in 6 mL of water and 1 mL of 10% NaOH added The reaction became milky turbid The suspension was shaken three times with 10 mL of benzene, dried over MgSO ₄ overnight and the solvent was removed in vacuo.

Yield: 158 mg (1.1 mmol) of (+) - R-bornylamine.

The bornylamine and 134 mg (1.1 mmol) of propanesultone were in 2ml abs. Benzen dissolved and kept under reflux for two hours. This formed a precipitate. After cooling, it was filtered off with suction through a frit, washed with benzene and dried in air.

Yield: 260 mg (0.9 mmol, 86%) C ₁₃ H ₂₆ O ₃ NS = 275.41

[α] ² , ² = + 30.6 ° (c = 1.01, EtOH)

calc.%: C = 56.69 H = 9.15 N = 5.09 S = 11.64

%. C = 56.67 H = 9.10 N = 5.2 S = 11.2

Example 4

722μΙ (4mmol) (-) - L-menthylamine and 420μΙ (4mmol) of 1,4-butane sultone were added in 5ml abs. Toluen heated for eight hours in a boiling water bath. The solvent was removed in vacuo, the residue was washed several times with a little cold ether and dried in vacuo. Brittle, transparent crystals were obtained.

Yield: 1.05 g (3.6 mmol, 90%) C ₁₄ H ₂₉ O ₃ NS = 291.43 [α] ²² = -40.3 ° (c = 1.05, EtOH)

calc.%: C = 57.69 H = 10.03 N = 4.81 S = 11.00

%. C = 56.64 H = 10.14 N = 5.0 S = 11.5

Example 5

244 mg (2 mmol) of 1,3-propane sultone were added to a warm solution of 420 mg (2 mmol) of "L-base" (see above) in 5 mL abs of methanol and the batch was boiled for three hours separated, washed with ether and dried in vacuo.

Yield: 487 mg (1.5 mmol, 73%) C ₁₂ H ₁₈₇ O ₇ N ₂ S = 334.32 Ia] "= -48.7 ° (c = 1.01, H ₂ O)

calc.%: C = 43.10 H = 5.43 N = 8.38 S = 9.59

%. C = 43.32 H = 5.65 N = 8.7 S = 9.5

Example 6

230 mg (2 mmol) of (+) - D-proline and 244 mg (2 mmol) of 1,3-propane sultone were dissolved in 2 ml abs. Given ethanol. The batch was immediately milky and kept boiling for two hours. After cooling, the product was filtered off with suction, the precipitated crystals were washed with ether and dried in vacuo.

Yield: 258 mg (1.1 mmol, 54%) C ₈ H ₁₆ O ₆ NS = 237.27 [α] ² , ² = + 24.4 ° (c = 1.05, H ₂ O)

calc.%: C = 40.49 H = 6.37 S = 13.51

%. C = 40.65 H = 6.24 S = 12.7

Example 7

576 mg (5 mmol) of (-) - L-proline were dissolved in 10 ml of abs. Ethanol was refluxed for 24 hours with 0.80 ml (7.7 mmol) of 1,4-butanesultone, the solvent was removed in vacuo, the residue was washed several times with ether and dried in vacuo. Yield: 610 mg (3.99 mmol, 80%) C ₉ H ₁₇ O ₆ NS = 251.31 [α] ² , ² = -16.4 ° (σ = 1.83 m EtOH) calc.%: S = 11, 01 N = 4.81

%. S = 11.8 N = 4.9

Example 8

372 mg (2 mmol) of N-methylglucamine were in 4ml abs. Dissolved methanol and added 244 mg (2 mmol) of 1,3-propane sultone. The reaction was refluxed for three hours. After cooling, the crystalline precipitate on the frit was washed several times with ether and dried in vacuo.

Yield: 469 mg (1.48 mmol, 74%) C ₁₀ H ₂₂ O ₈ NS = 316.34 [α] ² , ² = -18.9 ° (с = 1.01, H ₂ O)

Calc.%: C = 37.97 H = 7.01 N = 4.43 S = 10.13

% F: C = 37.44 H = 7.68 N = 4.4 S = 10.0

Example 9

860 mg (5 mmol) of L-valine tert-butylamide and 680 mg (5 mmol) of 1,4-butane sultone were dissolved in 10 ml abs. Dissolved ethanol and heated to boiling for 10 hours. The alcohol was then removed in vacuo and the reaction product was purified by column chromatography on silica gel with the eluent CH ₂ Cl ₂ / MeOH (7: 3, v / v). Yield: 850 mg (2.76 mmol, 55%) C ₁₃ H ₂₈ O ₄ N ₂ S = 308.44 [α] ² , ² = -13.66 ° (с = 1, EtOH) mp = 126 ° C , IR = 1 200.1 050 / cm.

Claims (4)

1. A process for the preparation of chiral water-soluble ammonium alkanesulfonic acids and their salts and sulfobetaines of the general formula I, R * ¹ R ² R ³ N ⁺ CHR ⁴ (CH ₂ ) _n SO ₃ ~ I in the R * ¹ = R ² = R ³ chiral alkyl, cycloalkyl, arylalky! or aryl alkenyl, R ^ = R ² with above-mentioned meaning and R ^{3 is} hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, arylalkyl, arylalkenyl or substituted alkyl,
or R * ¹ with the meaning given above or also carboxyalkyl and R ² = R ^{3 is} hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, arylalkyl, arylalkenyl or substituted alkyl,
or R * ¹ with the meaning given above or also carboxyalkyl and R ² and R ^{3 may be} the same or different, hydrogen, alkyl, aryl, cycloalkyl, Cycloalkenyl, arylalkyl, arylalkenyl or substituted alkyl and
R ^{4 is} hydrogen or alkyl in that a chiral primary, secondary or tertiary amine, imide or an amino acid of the general formulas II, III and IV, R ^ NH ₂ Il R * ¹ R ² NH Ml R * ¹ R ² R ³ N IV in which R * ¹ , R ² and R ^{3 have} the abovementioned meanings, with an aliphatic sultone of the general formula V, R ⁴ - CH - 0 I I V (CH ₂ ) _n - So ₂ in the R ^{4 has} the abovementioned meaning and η is an integer equal to 2 or 3, or is reacted with tolylsulfone at temperatures between 0 and 200 ° C in a solvent. 2. The method according to claim 1, characterized in that the sultone used are the aliphatic sultones 1,3-propane, 1,3-butane or 1,4-butane sultone and also tolylsultone. 3. The method according to claim 1 and 2, characterized in that are used as the solvent ethers, aromatics, other protic and non-protic solvents or solvent mixtures. 4. The method according to claim 1 to 3, characterized in that the reaction takes place at a temperature between 20 and 120 ⁰ C.