RU2360866C1 - Method of obtaining cis-dichlorodiisopropylamineplatinum (ii) - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: pure salt of cis-dichlorodiisopropylamineplatinum (II) has biological activity and can be applied in medicine and pharmaceutics. Potassium tetrachloroplatinate(II) is dissolved in water solution of isopropylamine chloride at room temperature, to obtained solution solution of isopropylamine is added. Deposited cis-dichlorodiisopropylamineplatinum (II) salt is filtered, washed with alcohol and dried.

EFFECT: increase of target product output and exclusion of product contamination.

3 tbl, 3 ex

Description

The invention relates to methods for producing pure platinum (II) compounds, namely cis-dichlorodiisopropylamineplatinum (II), which has antitumor activity.

The method of producing cis-dichlorodiisopropylamineplatinum (II) is based on the amination reaction of K ₂ PtI ₄ with the formation of cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ I ₂ ], followed by precipitation of AgI and the addition of KCl, which leads to the formation of cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] [1].

Closest to the claimed is a method for producing cis-dichlorodipropylamineplatinum (II), based on the interaction of potassium tetrachloroplatinate (II) with propylamine [2].

10 g of pure potassium chloroplatinate is dissolved in 100 ml of water in the cold and 25 ml of aqueous 33% propylamine are added. After some time, a yellow precipitate is formed. After 24 hours, a quantitatively yellow crystalline precipitate precipitated, very slightly contaminated with a small admixture of red salt [Pt (C ₃ H ₇ NH ₂ ) ₄ ] · [PtCl ₄ ], which was recrystallized from a hot hydrochloric acid solution. The yield of pure cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] is 6.5 g and 70%, respectively. This salt is a pale yellow crystalline powder.

The disadvantage of this method, as well as the previous one, is the low yield of the main product, as well as the need for recrystallization. In the synthesis [1], a silver solution is used, which can contaminate the main product.

The aim of the invention is to increase the yield and purity of cis-dichlorodiisopropylamineplatinum (II).

The goal is achieved:

- using high purity K ₂ PtCl ₄ [3].

- the creation of an optimal ratio of the concentration of the complex in solution and isopropylamine in concentrated hydrochloric acid.

The essence of the proposed method is as follows.

The potassium tetrachloroplatinate (II) salt is dissolved in an aqueous solution of isopropylamine chloride at room temperature. Isopropylamine is added to the solution. The precipitated salt of cis-dichlorodiisopropylamineplatinum (II) is filtered off, washed with alcohol and dried. The basis of the proposed method for producing cis-dichlorodiisopropylamineplatinum (II) is based on the following new data. The maximum accumulation in the solution of isopropylamine chloride was found depending on the reaction time. The reason for the appearance of side processes of amination, the formation of a double salt of the platinum (II) complex, the isomer of the platinum (II) complex, is established, and their contributions to the preparation of the final product are minimized.

Comparison with the prototype shows that the proposed method has the following advantages:

- the amination reaction is carried out by isopropylamine,

- the process of obtaining the complex does not require recrystallization, as a result, we obtain an increase in the yield and purity of the main product of cis-dichlorodiisopropylamineplatinum (II) up to 80%.

Example 1. To 8 g of K ₂ PtCl ₄ (1.92 · 10 ^-2 mol) add 6.44 g of iC ₃ H ₇ NH ₂ · HCl (6.74 · 10 ^-2 mol) in 50 ml of H ₂ O. Then, 1.65 ml of iC ₃ H ₇ NH _{2 was} added to the solution of this mixture at room temperature. After 2 hours, the process ends. The precipitated pale yellow precipitate was filtered off, washed with alcohol and dried. The amount of the isolated cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl] complex is 5.90 g, which is 80% of the theoretical. The complex compound cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] was characterized by the following methods: PCTA, elemental analysis (Table 1), UV spectrophotometry (Table 2), and IR spectroscopy (Table 3). ) Impurities of [Pt (i-C ₃ H ₇ NH ₂ ) ₄ ] [PtCl ₄ ], trans- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] and KCl were not detected. For the cis- [Pt (iC ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] salt, an X-ray diffraction study was carried out for the first time, the parameters of a monoclinic cell with the symmetry group P2 _{1 / s were} determined a = 16.870 (3) Å, b = 10.788 (4) Å, c = 6.872 (4) Å, β = 97.750 ° (3), V = 1149.61 Å ³ , Z = 4.

Table 1 Elemental analysis cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] Pt Cl N FROM N Found: 50.84 18.37 7.35 18.80 4.74 Calculated: 50.78 18.45 7.29 18.74 4.68

table 2 Molar absorption coefficients ε (mol ^-1 l cm ^-1 ) of the cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] complex synthesized according to the procedure described above ν · 10 ^-3 , cm ^-1 41 40 39 38 37 36 35 34 33 32 31 thirty ε, (mol ^-1 l cm ^-1 ) 142.1 118.4 130.5 163.2 200.3 215.4 209.2 195 177.4 145.5 104.3 72,2

Table 3 The assignment of absorption frequencies cm ^-1 in the IR spectra of the complex compound cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] cis- [Pt (iC ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] Attribution 3248 3211 ν (NH) 3131 2975 2929 ν (CH) 2875 1592 1572 δ (NH ₂ ) 1509 1462 δ _as (CH ₃ ) 1388 δ _s (CH ₃ ) 1370 δ (CH) 1250 ω (NH ₂ ) 1160 ν (C-C) 1111 τ (NH ₂ ) 1070 940 ρ (CH ₃ ) 762 ρ (NH ₂ ) 440 ν (Pt-N)

Example 2. To 15 g of K ₂ PtCl ₄ (3.61 · 10 ^-2 mol) add 12.07 g of iC ₃ H ₇ NH ₂ · HCl (1.26 · 10 ^-2 mol) in 95 ml of H ₂ O. Then, 6 ml of i-C ₃ H ₇ NH _{2 was} added to the solution of this mixture at room temperature. After 1 hour, the process ends.

The precipitate formed is filtered off, washed with alcohol and dried. The amount of the isolated cis- [Pt (iC ₃ H ₇ NH ₂ Cl ₂ ] complex was 8.30 g, which is 70% of the theoretical. The precipitated salt was characterized by the following methods: PCTA, elemental analysis, UV spectrophotometry, and IR spectroscopy. Found an admixture of [Pt (i-C ₃ H ₇ NH ₂ ) ₄ ] [PtCl ₄ ].

Example 3. To 12 g of K ₂ PtCl ₄ (2.84 · 10 ^-2 mol) add 9.66 g of iC ₃ H ₇ NH ₂ · HCl (1.01 · 10 ^-2 mol) in 75 ml of H ₂ O. Then, 1.3 ml of iC ₃ H ₇ NH _{2 was} added to the solution of this mixture at room temperature. After 4 hours, the process ends. The precipitate formed is filtered off, washed with alcohol and dried. The amount of the isolated cis- [Pt (i-C ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] complex is 9.22 g, which is 83% of the theoretical. The released salt was characterized by the following methods: PCTA, elemental analysis, UV spectrophotometry and IR spectroscopy. An admixture of trans- [Pt (iC ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] salt was detected.

Example 1 shows the optimal conditions for obtaining both the concentration of platinum in solution and the purity of the main product. A change in the concentration of the initial complex in solution in the direction of increase is impossible due to its limited solubility in concentrated chloride medium. A decrease in the concentration of the starting complex in the solution will lead to a decrease in the yield of the main product. The increase in the concentration of isopropylamine in the solution is accompanied by a deeper amination of the platinum (II) complex in the solution, which reduces the yield of the main product and contaminates with the double salt [Pt (iC ₃ H ₇ NH ₂ ) ₄ ] [PtCl ₄ ] (example 2). The decrease in the concentration of isopropylamine leads to a longer reaction, contamination of the main product with the salt of trans- [Pt (iC ₃ H ₇ NH ₂ ) ₂ Cl ₂ ] (example 3). Thus, this method allows to obtain a complex salt of cis-dichlorodiisopropylamineplatinum (II) in high yield, without impurities (example 1).

Information sources

1. M.J. Clear, J.D. Hoeschele Studies on the Antitumor activity of Group VIII Transition Metal Complexes Part 1. Platinum (II) Complexes. Bioinorganic Chemistry. - 1973. V.2. - P.187-210.

2. S.M. Jergensen. On the structure of platinum bases. // Izv. Institute for the study of platinum and other precious metals. - 1933. issue 11. - S.159-203.

3. A.K. Starkov, V.I. Kazbanov, T.K.Kazbanova, V.V. Borisov, N.P. Sokolova, L.M. Malinovskaya. A method of producing tetrachloroplatinate (II) potassium or ammonium. - A.S. USSR No. 1649771, 01/15/1991.

Claims (1)

A method of producing cis-dichlorodiisopropylamine platinum (II) from an aqueous solution of potassium tetrachloroplatinate (II) using isopropylamine, characterized in that the potassium tetrachloroplatinate (II) solution is reacted with isopropylamine chloride and treated with a solution of isopropylamine.