JPH0144193B2 - - Google Patents

Description

[Detailed description of the invention] The present invention is based on the general formula (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH(CH ₂ ) _o X
・(HY) _p (where m and n are integers, p is 0 or a positive number, R
provides a haloalkylamino group-substituted trialkoxysilane represented by an alkyl group, X and Y are halogen atoms, and a method for producing the same. Conventional functional alkylsilane compounds, such as 3-
It is known that functional propylsilane compounds such as aminopropyltriethoxysilane and 3-(glycidyloxy)propyltriethoxysilane are used as water repellent treatment agents for fiber surfaces, rust preventive agents, and the like. The present inventor has continued research on the synthesis and utilization of various useful functional organosilicon compounds for many years. As a result, aminoalkyltrialkoxysilane represented by the general formula, (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH ₂ (where m is an integer, R is an alkyl group) and the general formula
By reacting with a halogen compound represented by (CH ₂ ) _o Y (where n is an integer and X and Y are halogen atoms), a new compound of the general formula (RO) ₃ SiCH ₂ CH ₂ CH ₂ ( NHCH ₂ CH ₂ ) _n NH(CH ₂ ) _o X
・(HY) _p (where n and m are integers, p is 0 or a positive number, R
We succeeded in synthesizing a haloalkylamino group-substituted trialkoxysilane represented by the alkyl group (X and Y are halogen atoms). Thereafter, the structure and uses of the above compound were confirmed, and the present invention was completed and provided. The haloalkylamino group-substituted trialkoxysilane, which is a new compound of the present invention, has the general formula: (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH(CH ₂ ) _o X
・(HY) _p (where m and n are integers, p is 0 or a positive number, R
is an alkyl group, and X and Y are halogen atoms). The haloalkylamino group-substituted trialkoxysilane and its hydrohalide salt are usually yellowish solids, and are generally confirmed to be each compound of the general formula by the following methods (a) to (d). You can. (a) Measurement of the infrared absorption spectrum (hereinafter sometimes abbreviated as ir) shows a wide range of absorption based on NH bonds around 3400 cm ^-1 . (b) By measuring the mass spectrum (hereinafter sometimes abbreviated as ms), the composition formula corresponding to each peak (generally the mass number expressed as m/e, which is the ion mass m divided by the charge number e) can be determined. By calculating , it is possible to estimate the binding mode of the compound subjected to measurement. For example, in the case of the haloalkylamino group-substituted trimethoxysilane used in the present invention, strong peaks are usually observed at m/e192 and m/e160. (c) ¹³ carbon nuclear magnetic resonance spectrum (hereinafter ¹³ C−
By measuring (sometimes abbreviated as nmr), it is possible to know the number and type of methylene groups, methyl groups, etc. present in the compound subjected to measurement. For example, the approximate chemical shift values of each characteristic peak observed in ¹³ C-nmr of the haloalkylamino group-substituted trimethoxysilane in the present invention are as follows. (d) Calculate the weight percent of oxygen by determining the weight percent of each of carbon, hydrogen, nitrogen, halogen, and silicon through elemental analysis, and then subtracting the sum of the weight percent of each recognized element from 100. Therefore, the compositional formula of the compound subjected to measurement can be determined. General formula of the present invention (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH(CH ₂ ) _o X
・(HY) _p (where m and n are integers, p is 0 or a positive number, R
As described above, the haloalkylamino group-substituted trialkoxysilane represented by the alkyl group and the halogen atom (X and Y are halogen atoms) and its hydrohalide salt are usually yellowish and odorless solids.
The haloalkylamino group-substituted trialkoxysilane and its hydrohalide salt include methanol,
It is well soluble in ethanol, N,N-dimethylformamide, dimethyl sulfoxide, etc., but not very soluble in benzene, hexane, petroleum ether, etc. In addition, in water or a water-containing solvent, the alkoxy group in the haloalkylamino group-substituted trialkoxysilane molecule is hydrolyzed.
It tends to form Si--OH bonds and also Si--O--Si bonds, and when completely hydrolyzed, it yields an organosilicon polymer called polysilsesquioxane. The rate of the hydrolysis reaction is significantly accelerated by the presence of a small amount of acid or base in the reaction system. The haloalkylamino group is generally not changed by hydrolysis under normal mild conditions, and the haloalkylamino group remains in the polysilsesquioxane molecule that is the hydrolysis product. The haloalkylamino group-substituted trialkoxysilane and its hydrohalide salt of the present invention are generally stable without a solvent or in a solvent. Normally 100℃
It will melt if heated to a certain degree, and its fluidity will increase depending on the degree of heating. Also, if it is heated for a long time above 150℃, it tends to decompose and turn brown depending on the degree of heating. General formula of the present invention, (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH(CH ₂ ) _o X
・(HY) _p (where m and n are integers, p is 0 or a positive number, R
The method for producing the haloalkylamino group-substituted trialkoxysilane (wherein is an alkyl group and X and Y are halogen atoms) is not particularly limited, and any method may be used. A typical manufacturing method that is generally suitably employed will be described below. That is _, by reacting an aminoalkyltrialkoxysilane represented by the following formula with a halogen compound represented by _the general formula The haloalkylamino group-substituted trialkoxysilane and its hydrohalide salt of the invention can be obtained. The chemical formula for the above reaction is as follows. (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH ₂ X(CH ₂ ) n
Y ――――――――→ (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH (CH ₂ ) _o X
・(HY) _p The aminoalkyltrialkoxysilane represented by the above general formula is not limited to its manufacturing method, and for example, those obtained by known manufacturing methods can be used without particular restriction, but usually when m in the above general formula is 1 or 2 is preferably used. Also, general formula
A halogen compound represented by (CH ₂ ) _oY can also be used without being limited to its manufacturing method, but usually m in the general formula is represented by 1 to 6, and X and Y are the same or different chlorine, Those represented by bromine or fluorine atoms are preferably used. Specific examples of the halogen compound preferably used include ClCH ₂ Br,
_{ClCH2CH2Br , ClCH2CH2CH2Br , _}
Chloroalkyl bromides such as ClCH ₂ CH ₂ CH ₂ CH ₂ Br; Alkylene dibromides such as CH ₂ Br ₂ , BrCH ₂ CH ₂ Br; FCH ₂ Br, FCH ₂ CH ₂ Br,
_{FCH2CH2CH2Br , _}
Fluoroalkyl bromides such as FCH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ Br; ClCH ₂ CH ₂ Cl,
Examples include alkylene dichlorides such as ClCH ₂ CH ₂ CH ₂ Cl. In addition, in this reaction, hydrogen halide is produced as a by-product as the reaction progresses, and depending on the reaction conditions, the by-product hydrogen halide reacts with the target product, such as haloalkylamino-substituted trialkoxysilane, resulting in various reactions. Therefore, it is desirable to dissipate the hydrogen halide out of the reaction system by introducing an inert gas such as nitrogen gas or helium gas into the reaction system. Also, organic chlorine (e.g. triethylamine, tributylamine, pyridine, etc.) is used in the reaction system.
Alternatively, it is also an extremely desirable embodiment to add an inorganic base (eg, sodium carbonate, potassium carbonate, etc.) as a scavenger for the hydrogen halide. Representative examples of this reaction will be described in detail in the Examples below.
Although the reaction can generally be carried out without a solvent, it is generally carried out in the presence of a solvent. The solvent is not particularly limited and can be used as long as it is a polar nonaqueous solvent that does not react with the raw materials or the catalyst, and generally includes hydrocarbon solvents such as benzene, toluene, and hexane; dimethyl ether,
Ether solvents such as diethyl ether are used. Further, the reaction conditions are not particularly limited, but may vary depending on the type of raw materials, the type of catalyst, the presence or absence of a solvent, etc., so it is preferable to select suitable conditions in advance and carry out the reaction. Generally, it is sufficient to select a temperature of -20 to 160°C for a period of several tens of minutes to ten days. Furthermore, since the reaction proceeds sufficiently under atmospheric pressure, it is usually sufficient to carry out the reaction at normal pressure, but it can also be carried out under increased pressure or reduced pressure if necessary. Furthermore, as is clear from the above reaction formula, in order to obtain 1 mole of haloalkylamino group-substituted trialkoxysilane, the general formula
At least 1 mole of the halogen compound represented by (CH ₂ ) _o Y is required. However, the ease of separation of the above reaction generally varies to a considerable extent depending on the structure of the halogen compound used, and when a halogen compound with low reactivity is used in the reaction, more severe conditions are required. In addition to carrying out the reaction described below, the desired haloalkylamino group-substituted trialkoxysilane can often be obtained more efficiently when the halogen compound is used in a larger amount than the stoichiometrically required amount. In addition, when the halogen compound used has high reactivity, depending on the reaction conditions, only the terminal amino group described in the above reaction formula may be haloalkylated trialkoxysilane, that is, (CH ₃ O ) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH
In addition to the compound represented by (CH ₂ ) _o X or its hydrogen halide salt, the general formula (However, m and n are integers, X is a halogen atom, and x+y is represented by m+y>x+y>0) or a hydrogen halide salt thereof may also be obtained. Furthermore, when the halogen compound is used in an amount of 1 mole or less per mole of aminoalkyltrimethoxysilane during the reaction, in the above general formula, 1>x+y>0, x>0, y≧0
In some cases, a product represented by is obtained. After the completion of the reaction, the haloalkylamino group-substituted trialkoxysilane and its hydrohalide salt produced under the various reaction conditions described above can be recovered by removing the solvent by distillation and removing the excess general formula
When a halogen compound represented by (CH ₂ ) _o Y is used, the halogen compound remaining after the reaction can be isolated very easily by distilling it off together with the solvent. As the distillation means, in addition to normal pressure distillation, means such as reduced pressure distillation and vacuum distillation are preferably used. If an excess of the halogen compound is used in the reaction, or if a solvent with a relatively high boiling point such as N,N-dimethylformamide or diethylene glycol dimethyl ether is used, the target product, the halogenoalkylamino group-substituted trimester, may be removed during the distillation. In order to prevent thermal decomposition of the alkoxysilane and to obtain the desired product in a more pure manner, it is desirable to perform distillation under reduced pressure or vacuum distillation. Furthermore, depending on the type of solvent, for example, in the case of hexane, only the desired product becomes an insoluble solid and precipitates, so it can be easily isolated by removing the solvent etc. at an angle. . Although the haloalkylamino group-substituted trialkoxysilane of the present invention isolated by the above-described procedure is extremely pure, if a haloalkylamino group-substituted trialkoxysilane of even higher purity is required, recrystallization, column chromatography, A method such as reprecipitation may be used. Since the haloalkylamino group-substituted trialkoxysilane of the present invention contains a trialkoxysilyl group in its molecule that is easily dehydrated and condensed by hydrolysis, it can be Hydrolysis together with compounds gives various dehydration condensation products. Therefore, by applying this property, it can be used as a coating material that changes the surface condition of paper, wood, fiber cloth, glass, etc. Further, when the haloalkylamino group-substituted trialkoxysilane of the present invention is hydrolyzed under mild conditions alone or together with other hydrolytically polymerizable compounds, it becomes a haloalkylamino group-substituted polysilsesquioxane or a derivative thereof. The haloalkylamino group-substituted polysilsesquioxane obtained by this hydrolysis has excellent physiological activity, as is clear from the application examples described below, and is particularly effective against cancer cells such as Ehrlichi's cancer in mice. It exerts cancer effect. Such haloalkylamino group-substituted trialkoxysilanes and their hydrohalides are extremely useful new compounds that can be used for various purposes. The present invention will be explained in more detail with reference to the following examples and application examples, but the present invention is not limited to these examples and application examples. Example 1 Distilled purified r-(2-aminoethyl)aminopropyltrimethoxysilane (6.39g,
0.029 mole) was dissolved in ether (20 ml), chloroethyl bromide (23.85 g, 0.166 mole) was added, and the mixture was stirred at room temperature for 34 hours. The mixture was then heated to reflux for 8 hours. A small amount of colorless solid produced was separated, the yellow liquid was concentrated under reduced pressure, and the residue was further dried in vacuo to obtain a yellow candy-like solid (10.52 g). When the infrared absorption spectrum was measured by smearing it on a potassium bromide plate, it was found that 3400
Broad absorption based on NH bonds at cm ^-1 , 2950 cm ^- and
Absorption based on CH bond at 2830cm ^-1 , 1180cm ^-1 ~980
A broad absorption based on SiO bonds was observed at cm ^-1 . When the mass spectrum was measured, m/e192
In addition to the peak corresponding to (CH ₃ O) ₂ SiCH ₂ CH ₂ CH ₂ NHCH ₂ , characteristic strong peaks at m/e160 and m/e99 were shown. In addition, its elemental analysis values are C31.71%, H7.28%, N6.90%, Cl10.52%,
Si7.97% and composition formula C ₁₀ H ₂₆ N ₂ O ₃ ClBrSi
(365.80) is the calculated value of C32.83%, H7.17
%, N7.66%, Cl9.69%, Si7.68%.
Furthermore, ¹³ C-nuclear magnetic resonance spectrum (δ, ppm:
Tetramethylsilane (standard) was measured in methanol, and the analysis results were as follows. From the above results, the isolated product has the following formula (CH ₃ O) ₃ Si−CH ₂ CH ₂ CH ₂ NHCH ₂ CH ₂ NHCH ₂ CH ₂ Cl
It was revealed that it was r-(chloroethylaminoethyl)aminopropyltrimethoxysilane hydrobromide represented by ・HBr. Example 2 Distilled purified r-[2-(ethylenediamino)ethyl]aminopropyltrimethoxysilane (6.45
g, 0.024 mole) in ether (50 ml),
After adding chloroethyl bromide (24.51 g, 0.171 mole) and heating under reflux for one day, a green-yellow viscous solid precipitated at the bottom. The solution portion was decanted and the residue was dried in vacuo to give a yellow solid (9.80 g).
When we measured its infrared absorption spectrum, we found that 3400
Broad absorption based on NH bonds at cm ^-1 , 2950 cm ^-1
Absorption based on CH bond at 2830cm ^-1 , 1180cm ^-1 ~960
A broad absorption based on SiO bonds was observed at cm ^-1 . When the mass spectrum was measured, m/e192
In addition to the peak corresponding to (CH ₃ O ₃ )SiCH ₂ CH ₂ CH ₂ NHCH ₂ , a characteristic strong peak was also shown at m/e160. In addition, elemental analysis revealed that
C33.98%, H7.56%, N10.20%, Cl9.03%,
Shows a value of Si7.15%, composition formula
Calculated values as C ₁₂ H ₃₁ N ₃ O ₃ ClBrSi (408.86): C35.25%, H7.64%, N10.28%, Cl8.67%,
It matched with Si6.87%. Furthermore, the nuclear magnetic resonance spectrum was measured in methanol, and the analysis results were as follows. From the above results, it was revealed that the isolated product was a chloroethylamino group-substituted trimethoxysilane hydrobromide represented by the following formula. (CH ₃ O) ₃ SiCH ₂ CH ₂ CH ₂ NHCH ₂ CH ₂ NHCH ₂ CH ₂ NHCH ₂ CH ₂
Cl・HBr Example 3 r-(2-aminoethyl)aminopropyltriethoxysilane (8.46 g, 0.032 mole) and triethylamine (5.05 g) were dissolved in anhydrous benzene (80
ml). Furthermore, fluorohexyl bromide (15.23 g, 0.083 mole) was added to the mixture and stirred at room temperature overnight. The reaction mixture was further heated under reflux for 6 hours, then cooled, the precipitated hydrobromide of tritylamine was separated, and the liquid was concentrated and dried in vacuo to obtain a pale yellow solid (9.41 g). The product was subjected to instrumental analysis and elemental analysis in the same manner as in Example 1, and it was confirmed that the product was a fluorohexylamino group-substituted triethoxysilane represented by the following formula. ( _CH3CH2O ) _{3SiCH2CH2CH2NHCH2CH2NH} ( _CH2 ) _6F Example 4 r-( _{2 -} aminoethyl ₎ aminopropyltri _{( n -} propoxy)silane (8.58g, 0.028 mole)
was dissolved in anhydrous hexane (40 ml), and a solution of ethylene dipromide (5.58 g, 0.03 mole) in anhydrous hexane (10 ml) was added dropwise under ice water cooling. After the dropwise addition, the mixture was stirred at room temperature for 3 days, and then volatile components were removed by distillation. The residue was vacuum-dried to obtain r-(2-bromoethylaminoethyl)aminopropyltri(n-propoxy)silane (13.29 g) as a yellowish brown solid. The structure of the product is as in Example 1.
It was determined by the method described in . Reference Example 1 Dissolve r-(chloroethylaminoethyl)aminopropyltrimethoxysilane hydrobromide (10.39 g) obtained in Example 1 in methanol (30 ml), then add water (80 ml) and stir at room temperature. After stirring for 4 days, a small amount of precipitate was removed by filtration. The liquid was concentrated to dryness and dried under vacuum to obtain a chloroethylamino group-substituted polysilsesquioxane (9.22 g) represented by the following formula. Reference Example 2 The chloroethylamino group-substituted trimethoxysilane (9.78 g) obtained in Example 2 was mixed with methanol (80 g).
ml), then added water (200 ml) and stirred at room temperature for 2 days. The volatile components were removed by distillation and the residue was vacuum-dried to obtain a chloroethylamino group-substituted polysilsesquis represented by the following formula. Oxane (8.55g) was obtained as a yellow solid. Application Example Each chloroethylamino group-substituted polysilsesquioxane obtained in Reference Examples 1 and 2 was added to physiological saline to prepare a sample solution containing a specified amount of sample. The sample contains 1 x ¹⁰⁶ Ehrlichi cancer cells.
0.5ml each into the abdominal cavity of 6 CDF ₁ mice (female)
Continuous injections were administered for days. Based on the results of the 60-day life extension test, the mean survival time (MST) was calculated.
T/C% was accurately calculated using a computer by comparing with the average survival days of the control group (30 animals).
That is, the mean survival days (T) of the test subjects by this test
Calculate the average survival days (C) of the control and control animals, and calculate T/C x 100
(%) T/C was calculated. The results are shown in Table 1. Although 30 mice were used as a control group, the average value for 6 mice is shown in the table. 【table】

Claims (1)

[Claims] 1 General formula (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH(CH ₂ ) _o X
・(HY) _p (where m and n are integers, p is 0 or a positive number, R
is an alkyl group, and X and Y are halogen atoms). 2 Halogen compounds represented by the general formula X (CH ₂ ) _o Y (where n is an integer, X and Y are halogen atoms) and the general formula (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH ₂ (where m is an integer and R is an alkyl group) General formula (RO) ₃ SiCH ₂ CH ₂ CH ₂ (NHCH ₂ CH ₂ ) _n NH (CH ₂ ) _o
・(HY) _p (where m and n are integers, p is 0 or a positive number, R
is an alkyl group, and X and Y are halogen atoms.