Method for purifying ethylene cyanohydrin

Abstract

The present invention relates to a method for purifying ethylene cyanohydrin, comprising incubating technical-grade ethylene cyanohydrin product with at least one titanium(IV) alkoxide, and to an ethylene cyanohydrin product having a purity greater than 99% and containing less than 0.05% ethylene glycol (EG) and / or containing a water content of less than 1000 ppm.

Description

[Technical Field]

[0001] Technical field of the invention The present invention relates to a method for producing high-purity ethylene cyanohydrin.

[0002] Background of the Invention The production of ethylene cyanohydrin from ethylene oxide and hydrogen cyanide is well known in the art. To carry out these processes on an industrial scale, there are various solutions in the prior art:

[0003] U.S. Patent No. 2,653,162 describes the preparation of alkyl cyanohydrins by reacting alkyl oxides with hydrocyanic acid in the presence of a cation exchange resin having alkali metal carboxylate functional groups, which must be regenerated in a subsequent process step, which is very laborious.

[0004] U.S. Patent No. 2,364,422 discloses a method for preparing alkyl nitriles by reacting a tertiary alkyl epoxide with hydrocyanic acid. In an intermediate step, a cyanohydrin is formed, which is immediately hydrated.

[0005] In DE-B 1 232 570, ethylene oxide and liquid hydrocyanic acid are converted to ethylene cyanohydrin in an alkaline medium by pumping them through a closed tube circuit and transferring the reaction mixture to a post-reactor.

[0006] In WO 2007 / 144212, ethylene oxide and liquid hydrocyanic acid are converted to ethylene cyanohydrin in an alkaline medium.

[0007] CN109665974 further teaches that cyanohydrin synthesis generally requires a certain amount of base to promote the reaction. The cyanohydrin product is often unstable under such conditions. The decomposition products of hydrocyanic acid or some aldehydes are unexpected and unpredictable and often directly detectable by the darkening of the color of the cyanohydrin product. Furthermore, impurities and water introduced into the reaction or carried by the raw materials also exacerbate product decomposition and polymerization. To ensure product quality and stable storage requirements for a certain period of time, measures must be taken to enhance its stability. This is achieved by maintaining, handling, and storing the cyanohydrin under acidic conditions with a pH value below 7.

[0008] Bulk samples of ethylene cyanohydrin obtained from various plants are usually of high purity. This purity grade of ethylene cyanohydrin is preferably used as a preliminary product in the pharmaceutical and cosmetic industries.

[0009] However, even ethylene cyanohydrin that is described as being highly pure still contains impurities, particularly water and ethylene glycol, which prevent its use in highly sensitive applications such as medicinal chemistry and synthetic DNA / RNA chemistry.

[0010] In addition to the other aforementioned uses, ethylene cyanohydrin is commonly used in the synthesis of nucleosides, oligonucleosides, nucleoside phosphoramidites, and subsequent use in RNA and DNA sequence synthesis. For example, ethylene cyanohydrin is used to generate bis(diisopropylamino)(2-cyanoethoxy)phosphine, which is used to prepare phosphoramidite reagents required for the synthesis of oligodeoxynucleotides, as a phosphorylating agent in the synthesis of 1,2-diacyl-sn-glycerophosphatidylserine, for the in situ preparation of deoxyribonucleoside phosphoramidites, in the preparation of 2'-deoxy-2'-fluoro-3'-O-(β-cyanoethyl-N,N-diisopropylphosphoramido)-5'-O-(4-methoxytrityl)-4'-thio-β-D-arabinolidine and 1-(3-O-(β-cyanoethyl-N,N-diisopropylphosphoramido)-2-deoxy-2-fluoro-5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-arabinofuranosyl)-thymine, and as a reagent for synthesizing phosphorylated nucleotides.

[0011] Ethylene cyanohydrin is also an important source of the disubstituted derivative bis(2-cyanoethoxy)-N,N-diisopropylaminophosphine, which is also a useful phosphorylating reagent in oligonucleotide synthesis for adding terminal phosphate groups to 3' or 5' hydroxyl functions. Another derivative based on ethylene cyanohydrin is chloro(diisopropylamino)-β-cyanoethoxyphosphine, which is used for the selective monophosphorylation of carbohydrates and nucleosides, to convert protected ribonucleosides to phosphoramidites, as a phosphitylating agent for 3'-hydroxyl groups in the synthesis of oligodeoxyribonucleotides, and in scalable solution-phase oligonucleotide synthesis utilizing phosphoramidite chemistry and DMT-, iBu-, and Bz-protected monomers.

[0012] In nucleoside synthesis, the 2-cyanoethyl group is considered both a powerful protecting group and a modifiable substituent at the phosphorus atom. Phosphites are typically protected with the base-labile 2-cyanoethyl group. The 2-cyanoethyl group is introduced via alcoholysis of a basic phosphorus-containing precursor and ethylene cyanohydrin, making this alcohol of great industrial importance.

[0013] Generally, phosphorus-containing molecules with -OCH2CH2CN substituents are obtained by reacting phosphorus-containing precursors with an appropriate (basic) leaving group with ethylene cyanohydrin, or by reacting phosphorus-containing precursors with other substituents (e.g., halides: Cl, Br, I), ethylene cyanohydrin, and acid scavengers, such as amines. More generally, phosphorus-containing molecules react with ethylene cyanohydrin or its corresponding alcoholates. If other R-OH or RO-containing contaminants are present in the reaction, side reactions can occur, as these contaminants can equally react and bond to the phosphorus atom. This can result in, for example, contaminated nucleosides, which may not function properly and lead to defects in DNA / RNA structure. Water, methanol, ethanol, and ethylene glycol (and their corresponding alcoholates) can convert -OH / O - All parts of the present invention are relevant and expressly incorporated herein by reference.

[0014] Therefore, the availability of high-purity ethylene cyanohydrin is significant, especially purity grades that do not contain water and / or ethylene glycol. Improved synthesis of phosphoramidites and their derivatives is possible only if high-purity ethylene cyanohydrin is synthesized and used. Unfortunately, industrial processes for the production of ethylene cyanohydrin result in products containing variable amounts of water and / or ethylene glycol.

[0015] The two most prominent methods of synthesizing ethylene cyanohydrin are: - A) Reaction of ethylene oxide with hydrocyanic acid (HCN) - B) (catalytic) addition of water to acrylonitrile In particular, pathway (B) is evident in product contamination with water, whereas pathway A allows for the formation of ethylene glycol from ethylene oxide.

[0016] Therefore, both variants result in products with poor impurity profiles, and the applications described above require significant additional efforts for purification and work-up.

[0017] In view of the above drawbacks, the object of the present invention was to provide a simple, resource- and cost-efficient method for purifying ethylene cyanohydrin that is applicable on an industrial production scale.

[0018] Summary of the Invention This problem is solved by the method according to the present invention. The inventors have surprisingly found that technical grade ethylene cyanohydrin (ECH) can be purified in a simple and cost-effective manner by incubating said technical grade ECH with at least one titanium(IV) alkoxide.

[0019] The term "technical grade ECH" in the context of the present invention refers to commercially available bulk ECH obtained directly from the reaction of ethylene oxide with hydrocyanic acid (HCN) or from the (catalytic) addition of water to acrylonitrile. The term "technical grade" refers to a product quality suitable for many industrial applications, where the product generally contains small amounts of impurities (ethylene glycol, water) and is less pure than pharmaceutical purity grade.

[0020] The term "incubating technical grade ECH with at least one titanium(IV) alkoxide" refers to contacting technical grade ECH with at least one titanium(IV) alkoxide for a specified period of time.

[0021] In accordance with the above, the present invention relates to a method for purifying ECH, comprising incubating technical grade ECH with at least one titanium(IV) alkoxide.

[0022] The method according to the present invention allows for the production of ECH products with novel product qualities, i.e., novel purities, in contrast to purification methods commonly known in the art (see comparative examples included herein).

[0023] More specifically, the method according to the invention allows the production of ECH with a purity of greater than 99%, containing less than 0.05%, preferably 0.01% or less ethylene glycol (EG) and / or containing a water content of less than 1000 ppm, typically less than 500 ppm.

[0024] Detailed Description of the Invention The present invention relates to a novel method for producing and / or purifying ECH, which comprises incubating technical-grade ECH product with at least one titanium(IV) alkoxide, and to a high-purity ECH product obtained by such method.

[0025] Titanium(IV) alkoxides are esters of orthotitanic acid, H4TiO4.

[0026] Titanium(IV) alkoxides suitable for the method according to the invention are, for example, Ti(OMe), Ti(OEt), Ti(OiPr) and Ti(OBu), where R=C1 to C 20 The linear or branched titanium(IV) alkylalkoxides are Ti(OR)4. Ti(OiPr4) is particularly preferred.

[0027] Advantageously, the titanium(IV) alkoxide used in the incubation step is present in an amount between 1% and 15% by weight, preferably between 5% and 10% by weight.

[0028] The incubation of technical-grade ECH with at least one titanium(IV) alkoxide can preferably be carried out with stirring, with the stirring speed particularly preferably being in the range of 50 to 2000 rpm, very particularly preferably being in the range of 100 to 500 rpm.

[0029] The incubation temperature can be 20°C to 70°C, preferably 25°C to 50°C.

[0030] The incubation time depends, inter alia, on the selected parameters, such as temperature. Generally, the incubation time should be between 0.5 and 20 hours, preferably between 2 and 18 hours. Those skilled in the art can find further information regarding reaction times in the accompanying examples.

[0031] Technical grade ECH can be obtained from the reaction of ethylene oxide with hydrocyanic acid (HCN) or from the (catalytic) addition of water to acrylonitrile.

[0032] To further increase the purity of ECH, a distillation step can be performed after incubation with titanium(IV) alkoxide. Distillation can be carried out by several techniques, such as using thin-film evaporators, short-hole evaporators, and fractional distillation apparatus with or without columns. Distillation can be carried out at ambient or elevated temperatures and ambient or reduced pressures, with both parameters adjusted to the physical properties of the ECH.

[0033] The method of the present invention can produce ECH with a purity of greater than 99% and containing less than 0.05% ethylene glycol (EG), preferably less than 0.01% ethylene glycol (EG). The purity and impurities of ethylene cyanohydrin, such as EG content, can be measured and quantified via gas chromatography (GC). For example, a gas chromatograph GC6890, 7890 (Agilent) or equivalent device equipped with an FID detector can be used in combination with a quartz capillary column (DB-FFAP, DB-WAX, or other separation phase, 30 m). Helium can be used as the carrier gas with injector and detector temperatures of 250°C. The area percent of the components is determined (automatically) by the area percent reporting option of the chromatographic control system. % is converted to ppm by multiplying by 10,000.

[0034] In one embodiment of the present invention, the ECH has a water content of less than 1000 ppm. A water content of less than 500 ppm is particularly advantageous. The water content of ethylene cyanohydrin can be determined by coulometric Karl Fischer titration, or alternatively, by volumetric titration. A Karl Fischer coulometer (e.g., Metrohm Type 756) is preferably used in conjunction with an analytical balance, a calibrated syringe, and a calibrated titration reagent.

[0035] Preferably, the ECH has an APHA color value (Pt / Co) of less than 30, preferably less than 5. The color value can be determined photometrically, in which visual comparison with standard color solutions on the platinum-cobalt scale is replaced by measurement of the absorbance of the sample at wavelengths of 460 nm and 620 nm. The absorbance difference E 460nm -E 620nm= ΔE is a linear relationship with the color units of platinum-cobalt standards. Plotting color values ​​against ΔE yields a calibration line whose slope serves as a "factor" for calculating color values, provided that the colorimetric specifications of the sample to be analyzed, i.e., its hue, largely correspond to the platinum-cobalt scale. A spectrophotometer or filter photometer equipped with filters in the 460 nm and 620 nm ranges is used with 5 cm and 1 cm cuvettes. Calibration materials are potassium hexachloroplatinate (K2PtCl6), cobalt(II) chloride hexahydrate (CoCl2 x 6H2O), and concentrated hydrochloric acid (PA32). Pt / Co standard solutions are prepared and measured in 5 cm cuvettes at 460 nm and 620 nm using a spectrophotometer or filter photometer equipped with the appropriate filters. (The reference cuvette contains demineralized water.) The Pt / Co color values ​​and these (E 460nm -E 620nm The extinction coefficient, set against the σ, exhibits a linear relationship. The slope of this linear calibration line can be determined graphically or by regression and serves as the basis for the calculation of Pt / Co color values ​​(b and m values). Pt / Co color value=((E 460nm -E 620nm )-b) / m (b = axis intercept, m = slope)

[0036] Synonyms for platinum-cobalt color value are APHA and Hazen number. [Brief explanation of the drawings]

[0037] [Figure 1] FIG. 1 shows the ethylene glycol content in the sump. [Figure 2] FIG. 1 shows the ethylene cyanohydrin content in the sump.

[0038] Example Ethylene cyanohydrin was obtained directly from the manufacturing plant and used as received. Samples were analyzed by GC / GC-MS (purity), Karl Fischer titration (water) and Pt / Co scale (APHA, color). Naturally, analytical data for different ECH manufacturing batches vary, hence the ranges given. [Table 1]

[0039] Comparative Example Attempts to purify ethylene cyanohydrin with the requirements of simultaneously reducing the water content, ethylene glycol content, color value, and increasing the ethylene glycol content by utilizing common methods known in the art:

[0040] Azeotropic distillation using a cosolvent Removal of water and / or other polar materials, for example, from the reactor by azeotropic distillation is known and has been investigated in the art.

[0041] Under Dean-Stark conditions, 200 g of ethylene cyanohydrin and 250 g of toluene were heated to reflux for 5 hours. The mixture was then allowed to cool to room temperature, and after phase separation, ethylene cyanohydrin was obtained as a yellow liquid. [Table 2]

[0042] Discussion: Azeotropic distillation with a co-solvent yields a product with reduced water content and increased ethylene glycol. Simultaneous reduction of water and ethylene glycol content was not achieved. Furthermore, the color value increased dramatically. Furthermore, the co-solvent must also be distilled from the product.

[0043] absorption The use of porous materials such as molecular sieves to remove water and / or other polar substances, for example, from liquids (or gases) is known and has been investigated in the art.

[0044] 100 g of ethylene cyanohydrin was mixed with thoroughly dried molecular sieves (4 Å, 10-20 wt%) and allowed to stand / dry for 10 days. The molecular sieves were removed by filtration. [Table 3]

[0045] Discussion: After absorption by molecular sieves, the color value of ethylene cyanohydrin increases. The water content decreases, and the ethylene glycol content also decreases, but to a lesser extent. Simultaneous reductions in the water content and ethylene glycol content were achieved, but the ethylene cyanohydrin content also decreased, and the color value increased.

[0046] Additionally, the formation of acrylonitrile was observed.

[0047] Note: Using larger amounts of molecular sieves is not economical and will not result in the improvements in purity and color described above.

[0048] Distillation 1 Distillation as a purification method is known and investigated in the art.

[0049] Distillations were carried out under a variety of conditions, for example, between 50°C and 150°C and negative pressures ranging from 1 mbar to 500 mbar. Representative samples are shown below: 100 g of ethylene cyanohydrin was distilled at reduced pressure (10-30 mbar) at 130-150° C. 81 g of a clear, colorless distillate was collected together with 18 g of a yellow-red residue. [Table 4]

[0050] Discussion: The distillation resulted in a clear, colorless distillate, thus effectively reducing the color value of ethylene cyanohydrin (removal of colorant by distillation). While ethylene glycol increased in the distillate, the water content decreased. A simultaneous reduction in water content and ethylene glycol content was not achieved. Additionally, the ethylene cyanohydrin content decreased.

[0051] Distillation 2 An increasing amount of ethylene cyanohydrin sample (1.5 kg) was distilled on a column with 20 theoretical plates. The sample was initially heated at total reflux, followed by collection and analysis of different distillation fractions (reflux ratio 2), with intermediate total refluxes between each fraction. The column pressure was set at 250 mbar. One additional sump probe was collected at each distillation fraction.

[0052] Observations: During the heating phase, a clear color change in the sump was observed (from colorless to brown). As the distillation time progressed, the color of the mixture increased. Furthermore, an unexpectedly large amount of liquid was collected in the cold trap (23% of the initially applied mass), which also constituted two phases.

[0053] The mixture was analyzed to determine the water content (via Karl Fischer method): [Table 5]

[0054] Apparently, water is formed during the distillation procedure, and the water content increases at the column head (as the boiler is low). Due to the good stripping effect of the water, most of the liquid is collected in the cold trap. To rule out material incompatibility between the distillation equipment and ethylene cyanohydrin, the feed sample was heated separately in a vial (above 100°C). A color change and an increase in water content (from 250 ppm to 510 ppm, +104%) were observed, which proves a decomposition process under the distillation conditions and rules out material incompatibility.

[0055] Additionally, the distillate and sump were analyzed via GC and GC-MS. The results indicate that new components are formed during the distillation procedure, as peaks not observed in the starting material arise. [Table 6]

[0056] As the ethylene glycol content in the sump decreases (increases in the distillate), and more side reactions occur and by-products are formed, the ethylene cyanohydrin content decreases. Furthermore, the color value of the sump constantly increases. Therefore, it is impossible to obtain high-purity ethylene cyanohydrin as a distillation residue obtained by evaporation of contaminants.

[0057] Furthermore, the distillate obtained under these conditions exhibits a significantly reduced ethylene cyanohydrin content. It is also contaminated with ethylene glycol and water, which build up in the vapor phase. Furthermore, water is constantly formed during sump temperature exposure, making it impossible to obtain an anhydrous distillate.

[0058] In summary, continuous distillation of crude ethylene cyanohydrin did not result in ethylene cyanohydrin of high purity suitable for further reaction in biochemical applications.

[0059] Column chromatography purification Column chromatography is known in the art as a method for purifying chemicals or separating chemicals from one another.

[0060] Column chromatographic purification of large volumes of liquid (over 100 tons) is uneconomical compared to methods such as distillation. However, chromatographic purification of ethylene cyanohydrin has been attempted.

[0061] Aluminum oxide: The column was loaded with aluminum oxide (90). The column was loaded with ethylene cyanohydrin using a feed pump (flow rate 2 mL / min, residence time approximately 5 min, 25°C). 650 g of crude ethylene cyanohydrin was chromatographed and 16 fractions (approximately 40 g each) were collected and analyzed. [Table 7]

[0062] Discussion: Effective purification of ethylene cyanohydrin by column chromatography was not possible under the applied conditions. An increase in water content and color value was observed in all collected fractions. Furthermore, no effect on the ethylene cyanohydrin and ethylene glycol contents was observed.

[0063] Tonsil 312 FF: The column was loaded with Tonsil 312 FF. The column was loaded with ethylene cyanohydrin using a feed pump (flow rate 2 mL / min, residence time approximately 3.8 min, 25° C.).

[0064] Discussion: The column packing was compressed / condensed, so no eluate could be obtained. Therefore, chromatographic purification of ethylene cyanohydrin using clay as absorbent is not possible.

[0065] Molecular sieves (3 Å): The column was loaded with molecular sieves (3 Å). Ethylene cyanohydrin was loaded onto the column using a feed pump (flow rate 2 mL / min, residence time approximately 4.7 min, 25°C). 660 g of crude ethylene cyanohydrin was chromatographed, and 16 fractions (approximately 40 g each) were collected and analyzed. [Table 8]

[0066] Discussion: Effective purification of ethylene cyanohydrin by column chromatography was not possible under the applied conditions. In all collected fractions, an increase in water content was observed, but the color value slightly decreased. Furthermore, no effect on the ethylene cyanohydrin and ethylene glycol contents was observed. Furthermore, the formation of acrylonitrile was observed.

[0067] Molecular sieves (4 Å): The column was loaded with molecular sieves (4 Å). Ethylene cyanohydrin was loaded onto the column using a feed pump (flow rate 2 mL / min, residence time approximately 5.3 min, 25°C). 655 g of crude ethylene cyanohydrin was chromatographed, and 16 fractions (approximately 40 g each) were collected and analyzed. [Table 9]

[0068] Discussion: Effective purification of ethylene cyanohydrin by column chromatography was not possible under the applied conditions. In all collected fractions, an increase in water content was observed, but the color value slightly decreased. Furthermore, no effect on the ethylene cyanohydrin and ethylene glycol contents was observed. Furthermore, the formation of acrylonitrile was observed.

[0069] Molecular sieves (13X): The column was loaded with molecular sieves (13X). Ethylene cyanohydrin was loaded onto the column using a feed pump (flow rate 2 mL / min, residence time approximately 5.2 min, 25°C). 661 g of crude ethylene cyanohydrin was chromatographed, and 16 fractions (approximately 40 g each) were collected and analyzed. [Table 10]

[0070] Discussion: Effective purification of ethylene cyanohydrin by column chromatography was not possible under the applied conditions. In all collected fractions, an increase in water content was observed, but the color value slightly decreased. Furthermore, no effect on the ethylene cyanohydrin and ethylene glycol contents was observed. Furthermore, the formation of acrylonitrile was observed.

[0071] Activated carbon (Epibon Y 12x40 special (Donau Carbon)): The column was loaded with activated carbon. Ethylene cyanohydrin was loaded onto the column using a feed pump (flow rate 2 mL / min, residence time approximately 5.4 min, 25°C). 662 g of crude ethylene cyanohydrin was chromatographed, and 16 fractions (approximately 40 g each) were collected and analyzed. [Table 11]

[0072] Discussion: Effective purification of ethylene cyanohydrin by column chromatography was not possible under the applied conditions. In all collected fractions, an increase in water content was observed, but the color value decreased only slightly and initially. Furthermore, no effect on the ethylene cyanohydrin and ethylene glycol contents was observed.

[0073] Silica gel (silica gel 60, 0.060-0.2 nm): The column was loaded with silica gel. Ethylene cyanohydrin was loaded onto the column using a feed pump (flow rate 2 mL / min, residence time approximately 3.8 min, 25 °C). 655 g of crude ethylene cyanohydrin was chromatographed, and 16 fractions (approximately 40 g each) were collected and analyzed. [Table 12]

[0074] Discussion: Effective purification of ethylene cyanohydrin by column chromatography was not possible under the conditions applied. In all collected fractions, an increase in water content was observed, but the color value decreased slightly and only initially. Furthermore, no effect on the ethylene cyanohydrin and ethylene glycol contents was observed. Furthermore, the formation of acrylonitrile was observed.

[0075] Recrystallization Recrystallization as a method for purifying materials is known in the art, however, recrystallization of liquid ethylene cyanohydrin (mp: -46°C) to purify materials is not a viable process for obvious reasons.

[0076] Examples according to the present invention Purification of ECH by addition of titanium(IV) alkoxides An ester of orthotitanic acid H4TiO4, such as Ti(OR4) (R = Me, Et, iPr, Bu, 2-ethylhexyl, neopentyl, etc.), is stirred with ethylene cyanohydrin at ambient conditions for 2 hours.

[0077] Example 1a: A 100 g sample of technical grade ethylene cyanohydrin was mixed with Ti(OiPr)4 (5 g, 5 wt%) and stirred at 25°C for 2 hours. [Table 13]

[0078] Example 1b: A 100 g sample of technical grade ethylene cyanohydrin was mixed with Ti(OMe)4 (5 g, 5 wt%) and stirred at 50°C for 3 hours. [Table 14]

[0079] Example 2: A 20 g sample of technical grade ethylene cyanohydrin was mixed with Ti(OiPr)4 (2 g, 10 wt%) and stirred at 25°C for 18 hours. [Table 15]

[0080] Example 3: 537 g of technical-grade ethylene cyanohydrin sample was mixed with Ti(OiPr)4 (50 g, 10 wt%) and stirred at 25°C for 18 hours. The mixture was then evaporated using a rotary evaporator. First, the fore distillate was collected (15 wt%) at temperatures between 25°C and 150°C and pressures between 20 mbar and 60 mbar. The main distillate was collected (65 wt%) at 150°C and pressures between 10 mbar and 20 mbar. The residue (20 wt%) was retained. [Table 16]

[0081] Example 4: A 516.5 g sample of technical grade ethylene cyanohydrin was mixed with Ti(OiPr)4 (51.7 g, 10 wt %), heated to 50°C, and stirred for 4 to 20 hours. The mixture was then fractionally distilled at elevated temperature (50°C to 140°C, usually 90°C to 130°C) under vacuum (500 mbar to 1 mbar, usually 20 mbar to 5 mbar). The overall distillation yield of ethylene cyanohydrin is greater than 90%, typically greater than 95%.

[0082] To ensure the long-term stability of the distillate, the pH value of the product must be acidic and therefore below 7. [Table 17]

[0083] In contrast to all previous attempts, ethylene glycol content and water content were reduced, with a concomitant increase in ethylene cyanohydrin content and a decrease in color value to ethylene cyanohydrin.

Claims

1. The process comprises incubating technical grade ethylene cyanohydrin (ECH) with at least one titanium (IV) alkoxide, wherein the titanium (IV) alkoxide is Ti(OMe) ４ , Ti(OEt) ４ , Ti(OiPr) ４ and Ti(OBu) ４ A method for purifying ethylene cyanohydrin selected from the group consisting of:

2. 10. The method of claim 1, wherein the titanium (IV) alkoxide used in the incubation step is present in an amount of 1% to 15% by weight.

3. Alkyl titanate is Ti(OiPr) ４ The method according to claim 1 or 2, wherein

4. 4. The method according to any one of claims 1 to 3, wherein the incubation step is carried out at a temperature between 20°C and 70°C with stirring.

5. 5. The method according to any one of claims 1 to 4, wherein the incubation step is carried out at a temperature between 25°C and 50°C with stirring.

6. 6. The method according to any one of claims 1 to 5, wherein the incubation time is between 0.5 hours and 20 hours.

7. 7. The process of any one of claims 1 to 6, wherein technical grade ethylene cyanohydrin is obtained by reacting ethylene oxide with hydrocyanic acid (HCN).

8. 8. The process of claim 1, wherein technical grade ethylene cyanohydrin is obtained by catalytic addition of water to acrylonitrile.

9. 9. The process of any one of claims 1 to 8, further comprising a distillation step.

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