Making ethylenediaminetetraacetic acid

Abstract

To provide a composition comprising a diacid / dinitrile compound (DADN).SOLUTION: The present invention provides a composition that comprises a compound with the structure DADN illustrated below. In the formula, each -R is -CH2C(O)OM (M being independently hydrogen, an alkali metal, or a mixture thereof).SELECTED DRAWING: None

Description

Summary of the Invention [Problem to be solved by the invention]

[0001] Ethylenediaminetetraacetic acid (EDTA) is, for example, a metal ligand and / or a chiral It is a chemical compound that has many important industrial uses as a sedative. A commonly used process for producing A is to react with 1,2-dichlorophenyl ether in the presence of aqueous sodium hydroxide. It involves adding glycolonitrile (GN) to ethylenediamine (EDA). The problem with the process is that in addition to EDTA, the unwanted by-product nitrilotriacetic acid (NTA ) is produced. NTA is undesirable because it is suspected of being carcinogenic. It would be desirable to provide an improved method for making EDTA that reduces the formation of Another goal is to provide a method for making EDTA that minimizes the formation of color bodies. This is what we should do.

[0002] CN106045867A is ethylenediamine-N-N'-diacetate (DA) The first step is to add EDA to GN to form The dinitrile derivative (DN) of EDA is generated, and in the next step, DN is converted to DA. CN106045867A teaches how to make DA, but not how to make EDTA. It is desirable to provide a method for

[0003] The following is a description of the present invention.

[0004] The first aspect of the present invention is (a) A reaction mixture containing ethylenediamine (EDA) and glycolonitrile (GN) ( a) providing a reaction mixture (a) in an amount of about 1000 to about 15000 g / l based on the weight of the reaction mixture (a); 0% to 0.1% by weight of any compound having a pKa (pKaH) of 13 or more of a conjugate acid providing a base; (b) causing or allowing the reaction mixture (a) to react to form a compound of the structure DN forming a dinitrile compound having the formula: [ka] (c) contacting DN with an aqueous solution of a base having a pKaH of 11 or greater, and the resulting mixture causing or allowing to react to form a diacid compound having the structure DA. The method comprises the steps of: [ka] wherein each -R has the structure: [ka] wherein each M is independently hydrogen, or an alkali metal, or a mixture thereof; forming a (d) causing or enabling the DA to react sequentially or simultaneously with additional GNs; forming a product (Pd); (e) Cause the product (Pd) to react with a base that has a pKaH of 11 or greater. or allowing to form EDTA. This is a method for producing EDTA.

[0005] A second aspect of the invention is a composition comprising a compound having the structure DADN, [ka] wherein each -R has the structure: [ka] wherein each M is independently hydrogen, or an alkali metal, or a mixture thereof.

[0006] The following is a detailed description of the present invention. Unless otherwise indicated by the context, the following definitions is used herein.

[0007] The ratios presented herein are characterized as follows: For example, a ratio of 3:1 or more, the ratio may be 3:1, or 5:1, or 100:1. This characterization can be described in general terms as follows: When the ratio is said to be X:1 or more in this specification, the ratio is Y:1. where Y is greater than or equal to X. In another example, the ratio is said to be 15:1 or less. When used, the ratio may be 15:1, or 10:1, or 0.1:1, but It cannot be 0:1. Generally, the ratio is referred to herein as being less than or equal to W:1. means that the ratio is Z:1, where Z is less than or equal to W.

[0008] The following abbreviations are used herein to represent the following chemical structures: In the structure of -R has the same meaning. [Table 1-1] [Table 1-2]

[0009] As used herein, the term "very strong base" is defined as follows: A base is a compound that can bond to a hydrogen atom to form the conjugate acid of the base. The dissociation reaction of the conjugate acid is shown in reaction (I) below:

number

[0010] For example, hydroxide ion (OH - ) has a pKaH of 14 and is a very strong base. In another example, EDA has a pKaH of about 9.9 and falls into any of the following categories: Not applicable: Mildly strong base, moderately strong base, or very strong base.

[0011] When it is described herein that a compound is added to a vessel at a "constant rate," The period during which the compound is added is called "T 合計 " and label it as T 合計 Duration of 10% of the time, T 合計 of the times (labeled T10) that fall entirely within the Considering either interval, the rate of compound addition is the same as that of the compound added during T10, regardless of the selection of T10. The amount of compound added is 合計 Between 5% and 15% of the total of all compounds added In some cases, it is "stable."

[0012] The process of the present invention produces EDTA. The EDTA formed may be in the acid form, the salt form, or the like. or a mixture thereof. That is, in the structure shown above, each M can independently be: All four R groups on the EDTA molecule can be hydrogen or an alkali metal. can be hydrogen as M, or all four R groups on the EDTA molecule can be hydrogen as M. All R groups may be alkali metals, or the EDTA molecule may contain one or more R groups where M is hydrogen. and one or more R groups where M is an alkali metal. It is possible that a mixture of EDTA molecules with any number of R groups may exist.

[0013] The process of the present invention involves providing a reaction mixture (a). a) is probably composed of ethylenediamine (EDA) and glycolonite, among other compounds. Reaction mixture (a) contains very little or no very strong base. That is, there is no very strong base present in the reaction mixture (a) or there is no very strong base present in the reaction mixture (a). If any very strong base is present, the total amount of very strong base is The total amount of very strong bases is preferably 0 to 0.1% by weight based on the total amount of very strong bases. 03%, more preferably 0 to 0.01%, and more preferably zero.

[0014] Preferably, during step (a), the amount of moderately strong base in reaction mixture (a) is 0 to 0.1%, more preferably 0 to 0.03%, by weight based on the weight of the reaction mixture (a). , more preferably 0 to 0.01%, more preferably zero. Preferably, the reaction mixture The amount of the mildly strong base in (a) is from 0 to 0.1 by weight based on the weight of the reaction mixture (a). %, more preferably 0 to 0.03%, more preferably 0 to 0.01%, and more preferably zero. It is Ro.

[0015] Preferably, little or no hydroxide ions are present in reaction mixture (a). That is, preferably, the amount of hydroxide ions in the reaction mixture (a) is a) by weight based on the weight of the component (a), preferably 0 to 0.1%, more preferably 0 to 0.03%, and even more preferably The range is usually 0 to 0.01%.

[0016] In the reaction mixture (a), the molar ratio of GN to EDA is preferably 0.1:1 or more, more preferably 0.1:1 or more. Preferably 0.3:1 or more, more preferably 1:1 or more, more preferably 1.5:1 or more In the reaction mixture (a), the molar ratio of GN to EDA is preferably 3:1 or less, more preferably 1:1 or less. The ratio is preferably 2:1 or less.

[0017] The reaction mixture (a) may be at any temperature. Preferably, the reaction mixture (a) is The reaction mixture (a) is preferably at a temperature of 100° C., 0° C. or higher. ° C. or less, more preferably 50 ° C. or less, more preferably 25 ° C. or less, more preferably 10 ° C. The temperature is as follows.

[0018] The reaction mixture (a) can be formed by any method. For example, GN (neat or in aqueous solution) is placed in the vessel, and then EDA (neat or in aqueous solution) is added to the vessel at a constant rate. In another example, GN (neat or in aqueous solution) and EDA (neat or in aqueous solution) can be added simultaneously to the vessel in a semi-continuous process. In this embodiment (the "GN-added" embodiment), EDA (neat or in an aqueous solution) is placed in a vessel. Then GN (neat or in an aqueous solution) is added slowly (preferably at a constant rate) to the vessel. In these GN addition embodiments, the G in the vessel is preferably cooled before the start of the GN addition. The amount of N is 0 to 0.1%, preferably 0 to 0.1%, by weight of GN based on the weight of EDA in the container. It is 0 to 0.01%, and more preferably zero.

[0019] Preferably, the GN and EDA are used in a method of controlling the temperature of the resulting reaction mixture (a). GN is added to EDA, or EDA is added to GN, or Whether the two are added to the vessel simultaneously depends on whether the temperature ("TA") of the reaction mixture (a) is at a value of TA It is preferable to select conditions so as not to exceed -Max. The conditions are, for example, among the following: including one or more of: rate of addition, mechanical agitation, and / or externally applied via heat exchange. Preferably, TA-Max is 40° C. or less, more preferably 30° C. or less, and even more preferably The temperature is preferably 20° C. or lower, more preferably 15° C. or lower, and more preferably 10° C. or lower. Preferably, TA is 0° C. or higher.

[0020] Preferably, the EDA is added to the GN prior to contacting the EDA with the GN to form reaction mixture (a). is either neat or in an aqueous solution. Preferably, EDA is In an aqueous solution, preferably, the concentration of EDA is 30% to 50% by weight based on the weight of the aqueous solution. It is preferably 100%, more preferably 50% to 100%, and even more preferably 60% to 100%. In this specification, an aqueous solution having a concentration of 100% EDA is considered to be neat EDA and does not contain water. It means that it does not have.

[0021] Preferably, prior to contacting EDA with GN to form reaction mixture (a), GN is Preferably, the concentration of GN in the solution is 10% or more, more preferably The concentration of GN in the solution is preferably 20% or more, more preferably 30% or more. The degree is 70% or less, more preferably 60% or less, and more preferably 50% or less.

[0022] Preferably, all compounds in reaction mixture (a) other than EDA, GN, and water are The total amount is 0 to 3%, more preferably 0 to 1%, by weight based on the weight of the reaction mixture (a); More preferably, it is 0 to 0.3%, more preferably, it is 0 to 0.1%, more preferably, it is 0 to 0.0 It is 3%.

[0023] The reaction mixture (a) may be kept under an inert atmosphere or exposed to air. This is also fine.

[0024] In the practice of the invention, in step (b), a chemical reaction takes place in reaction mixture (a). , EDA reacts with GN to give a product ( Next, in step (c), DN is reacted with a mildly strong base (i.e., i.e., pKaH above 11 and below 12), or moderately strong bases (i.e., pKaH above 12 or stronger bases (i.e., pKaH of 13 or more). The aqueous solution containing the base is contacted with the base (Bc Preferably, the base (Bc) is a moderately strong base or a non-strong base. It is always a strong base, more preferably the base (Bc) is a very strong base.

[0025] Preferably, the base (Bc) is a hydroxide ion. is introduced as an aqueous solution of an alkali metal hydroxide, preferably sodium hydroxide. Potassium oxide may also be used.

[0026] The compound DN can be contacted with an aqueous solution of a base (Bc) by any method. Preferably, the mixture of products (Pb) formed in step (b) is subjected to further purification or Optionally, water is added to the product (Pb) prior to step (c). In some embodiments, the aqueous solution of base (Bc) may be DN (neat, or It is added slowly to a vessel containing either the iodine (Pb) or the product (Pb). In a preferred embodiment, DN (either neat, or in solution, or in product (Pb)) is slowly added to a vessel containing an aqueous solution of a base (Bc).

[0027] Regardless of the form of DN that is contacted with an aqueous solution of base (Bc), DN is In the embodiment in which the mixture containing DN and a base (Bc) is added to an aqueous solution of Under conditions that maintain the TC below the TC-Max value, DN gradually increases (preferably at 100 nm). The conditions are preferably adjusted by, for example, the rate of addition of DN, mechanical stirring, etc. and / or externally applied heating and / or cooling. Preferably, TC-Max is 90° C. or less, more preferably 70° C. or less, and even more preferably is 60° C. or less, more preferably 45° C. or less. Preferably, TC is 0° C. or more. .

[0028] In the aqueous solution of the base (Bc), prior to contact with the DN, the concentration of the base (Bc) is preferably , by weight based on the weight of the aqueous solution, is 10% or more, more preferably 20% or more, and even more preferably In the aqueous solution of the base (Bc), the concentration of the base (Bc) is preferably 30% or more. 75% or less, more preferably 70% or less, more preferably 6% or less, by weight based on the weight of the solution It is 5% or less, more preferably 55% or less, and more preferably 50% or less.

[0029] In step (c), the molar ratio of base (Bc) to DN is preferably 2:1 or more, more preferably In step (c), the ratio is preferably 3:1 or more, and more preferably 4:1 or more. Alternatively, the molar ratio of base (Bc) to DN is 6:1 or less, more preferably 5:1 or less. .

[0030] Preferably, the chemical reaction of step (c) is carried out at a temperature of 0° C. or higher, more preferably at a temperature of 10° C. or higher. Preferably, the chemical reaction of step (c) is carried out at a temperature below 100° C., more preferably Preferably, the temperature is 90° C. or lower, more preferably, 65° C. or lower, more preferably, 55° C. or lower, and even more preferably, is carried out at a temperature of 45°C or less.

[0031] In step (c), after combining DN and base (Bc), the resulting mixture is a diacid compound as defined above, which is caused or enabled to undergo an oxidative reaction A product containing DA (Pc) is formed. This reaction also produces ammonia, which It can be released into the atmosphere as ammonia gas or into the water as ammonium hydroxide. It is contemplated that the cellulose acetate solution may be dissolved in, or a mixture thereof. If the ammonia is dissolved in water, the ammonia is preferably removed. Examples include air sparging, nitrogen sparging, and vacuum distillation. If sparging is performed, chemical It can be carried out during the reaction or after the chemical reaction. Preferably, the amount of ammonia dissolved in water is The weight is based on the weight of ammonia produced in the chemical reaction that formed the product (Pc), % or less, more preferably 5% or less, more preferably 2% or less, more preferably 1% or less. be.

[0032] In the compound DA formed, the moiety M that binds to the carboxyl group is hydrogen, an alkali metal , or mixtures thereof. The preferred alkali metals are sodium or potassium. Preferably, the molar percentage of carboxyl groups in the DA molecule is an alkali metal. The percentage is preferably 50% or more, more preferably 75% or more, and even more preferably 90% or more.

[0033] Following step (c), step (d) is carried out. In step (d), The substance DA is contacted with GN. Some or all of the GN used in step (d) is All of the GNs used in steps (a) and (b) are added to the GNs used in steps (a) and (b). Step (d) is In a preferred embodiment, the method of the present invention is to generate a method for detecting a cellular component by using a method for detecting a cellular component. The product (Pc) is contacted with GN. Prior to contacting with the product (Pc), the GN is Preferably, it is in the form of an aqueous solution. Preferably, the concentration of GN in the aqueous solution is about 100% by weight of the aqueous solution. Preferably, the concentration in the aqueous solution is 25% or more, more preferably 35% or more, based on the weight of the aqueous solution. The concentration of GN should be 55% or less, more preferably 45% or less, by weight based on the weight of the aqueous solution. be.

[0034] In some embodiments, the GN (possibly in the form of an aqueous solution) is preloaded in the container. In some embodiments, the GN (probably Both products (Pc) in the form of an easily dissolved aqueous solution are slowly added to the vessel. In some embodiments, two consecutive sequences, one containing GN and the other containing the product (Pc), are The streams are contacted prior to adding the mixed stream to the vessel. is defined as above, the product (Pc) is present in the vessel, and GN is preferably constant. When GN is added gradually, the time required to add GN is The total time is preferably 30 minutes or more, more preferably 1 hour or more. When added, the temperature in the vessel ("TD") preferably remains above TD-Min. The conditions are selected such that the addition rate remains below the TD-Max. , mechanical stirring, and / or externally applied heating via heat exchange. Preferably, TDd-Min is 40° C. or higher, more preferably 100° C. or higher. The temperature is preferably 60° C. or higher, more preferably 80° C. or higher, and more preferably 90° C. or higher. Preferably, TD-Max is 120° C. or lower, more preferably 100° C. or lower.

[0035] In step (d), it is useful to estimate the molar ratio of GN to DA. The GN used for the evaluation is either or both of steps (a), (b), (c), and (d). includes the sum of all GN added during. Preferably, the molar ratio is 3. The molar ratio is 5:1 or more, more preferably 4:1 or more. Preferably, the molar ratio is 5:1 or less. More preferably, it is 4.5:1 or less, more preferably, it is 4.2 or less, more preferably, it is 4.1 or less. It is.

[0036] In carrying out step (d), DA and GN are reacted with each other to produce a product (Pd). The product (Pd) is probably Among the compounds are those containing the diacid / dinitrile compound DADN, as defined above. It is intended that:

[0037] Following step (d), step (e) is executed. In step (e), The substance (Pd) is in contact with an aqueous solution of a base with a pKaH of 11 or greater. Pd) is caused to react with a base having a pKaH of 11 or greater; or This reaction is believed to produce EDTA, among other compounds. The EDTA may be in the acid form, salt form, or a mixture thereof. It also produces ammonia, which can be released into the atmosphere as ammonia gas, or It is contemplated that it may be dissolved in water as ammonium hydroxide or a mixture thereof. As described above with respect to step (c), the ammonia dissolved in the water is removed. It is preferable that

[0038] In some embodiments, water containing DA, GN, and a base having a pKaH of 11 or greater. A mixture containing the solution is formed. In such an embodiment, DA and GN react to form DADN, which then reacts with a base having a pKaH of 11 or greater to form EDTA. Thus, in such an embodiment, all the same In the same vessel, step (d) occurs and then step (e) occurs.

[0039] In some preferred embodiments, the DA used in step (d) is In such an embodiment, GN and the product ( The mixture formed by combining Pc and Pd contains some base (Bc). It is expected that the base (Bc) reacts with DADN to produce EDTA. In these preferred embodiments, the sequence of chemical reactions that take place is steps (d) and including step (e) thereafter, but including all steps (d) and (e) required for both steps of reactants in the mixture formed by combining GN and product (Pc) Therefore, in these preferred embodiments, step ( e) occurs without the need to add any additional reactants.

[0040] In the compound EDTA that is formed, the moiety M that is bonded to the carboxyl group is hydrogen, alkali, Preferably, the metals are one or more alkali metals, more preferably one or more alkali metals. Preferably, M is an alkali metal, an alkali metal, or a mixture thereof. The mole percentage of the carboxyl group of the EDTA molecule, which is a lithium metal, is 50% or more, more preferably It is preferably 75% or more, and more preferably 90% or more.

[0041] After step (e) is completed, it is useful to characterize the composition of the resulting mixture. , herein labeled as product mixture (Pe). The amount of each compound is It is characterized as a weight percent based on the total solids weight of the mixture (Pe). The total solids weight of the substance (Pe) includes the weight of water and excludes the weight of ammonia. The product mixture (Pe) contains EDTA and ED3A. Preferably, EDTA The amount of is 10% or more, more preferably 15% or more, more preferably 20% or more. In some embodiments, the amount of EDTA is 50% or less.

[0042] In the product mixture (Pe), the amount of ED3A is preferably less than 10%, more preferably The ED3A is preferably 5% or less, more preferably 2% or less, and even more preferably 1% or less. It is not the desired product of the process. However, in some embodiments, The ED3A may be present in an amount of, for example, 0.1% or more or 0.2% or more in the product mixture (Pe ) may be present.

[0043] In the product mixture (Pe), preferably the amount of NTA is less than or equal to 3%, more preferably In the product mixture (Pe), in some embodiments, some NTA is present. Most preferably the amount of NTA is zero.

[0044] It is also useful to characterize the product mixture (Pe) by the weight ratio of EDTA to NTA. It is desirable to have this ratio as high as possible. Preferably, EDTA to NTA is 7:1 or more, more preferably 8:1 or more, more preferably 9:1 or more. .

[0045] Although the present invention is not limited to any particular mechanism, the NTA production in the process of the present invention is Regarding the reduction in the formation of GN, the following inference is made: the reaction of GN with a very strong base reduces NTA. In a previously known process, approximately 4 equivalents of G are reacted in the presence of caustic. N (i.e., 2 moles of GN for each -NH group on EDA) was mixed with EDA. In contrast, in the method of the present invention, steps (a) and (b) use about half the amount of GN( That is, one mole of GN for each -NH2 group on EDA (2 equivalents) reacts with EDA. Most or all of the GN reacts with EDA to form DN. In steps (a) and (b), there is little or no very strong base present, so In step (b), two equivalents of GN are consumed, and therefore in the presence of a very strong base When DN is converted to DA, NTA is not generated. That is, in the whole process of the present invention, About half of the GN used is consumed when it is not exposed to very strong bases. In the latter step (d) of the process of the present invention, some GN is reacted with a very strong base Generally, the present invention relates to contacting the G Reducing the amount of N and the contact between GN and very strong bases reduces the amount of NTA produced. It is expected that this will reduce

[0046] The following are examples of the present invention. The work was carried out at ambient temperature (approximately 100° C.) unless otherwise stated. The experiments were carried out at room temperature, also referred to as 23°C.

[0047] Example 1: Preparation of EDTA This was a laboratory-scale demonstration of the process of the present invention. A 1 L round bottom flask containing a stainless steel fritted gas sparger was placed under the liquid surface and 37.4 g of The reaction was cooled to 5° C., and the solution in the 1 L flask was then diluted with ethylenediamine. 160.0 g of 40 wt. % aqueous solution was added to the flask while stirring with overhead stirring at 0 rpm. Glycolonitrile was added over 127 minutes. The maximum temperature reached during the addition was 12°C. The solution was stirred at 5°C for 1 h and then at ambient temperature for 1 h, giving a pale yellow solution. 194.1 g of solution (98% mass recovery) was removed from the 1 L flask and poured into the addition funnel. The 1 L flask was rinsed with water and then 236.1 g of 50 wt % aqueous sodium hydroxide was added. 1 L of caustic solution was warmed to 40°C, then dinitrile solution was added through the dropping funnel. The mixture was added to the 1 L flask over 145 minutes using a stainless steel frit during the addition. An air sparge of 0.6 L / min was used to scrub the water through the solution. The heating mantle was dropped to allow for the addition to proceed smoothly, and the addition was paused when the temperature exceeded 42°C. The maximum temperature was 44°C. The resulting solution was pale orange in color. The pH increased from 4.95 to 5.51 during the addition and was 5.51 after an overnight hold at 40°C. A yellow solid formed overnight which rose to the condenser due to air sparging. The mixture was heated to 90°C and the yellow solid was dissolved in a 1 L flask. 6°C and run 0.6 L / min of evaporative cooling to provide reflux and rinse solid material from the condenser. Air sparging was re-established. An additional 26.5 g of water was added. The solids were dissolved and transferred to a 1 L reactor. After rinsing, the temperature was reduced to 95°C and then 206.5 g of 40% by weight aqueous glycolonite was added. The rill was added over a 2 hour period. Based on the temperature profile, no significant exotherm was detected. The maximum temperature reached during the feed was 95°C. The p of the scrubber at the end of the addition H was 10.02 and 9.95 after the red reaction solution was kept at 95°C for 3 hours. After cooling, 551.0 g of solution (82.7% mass recovery) was recovered and analyzed.

[0048] Example 2: Preparation of EDTA. This was a laboratory-scale demonstration of the process of the present invention. g (0.62 mol) of a 63 wt% EDA / water mixture was placed in a 1 L jacketed reactor. The jacket temperature was set to 20°C. Agitation was set to 300 rpm. 29.3 mL of a 40 wt% glycolonitrile solution (1.6 equiv., 1 mol) was added to the ISCO The EDA was added via pump at 5 mL / min over 26 min. The internal temperature of the reaction mixture The temperature rose from 23°C to 32°C during the addition. The jacket temperature was then set to 40°C. The reaction mixture was then held at that temperature for an additional 60 minutes to ensure complete conversion. The dinitrile reaction mixture was colorless to pale yellow at this time. 224.2 g (2.8 moles) of 50% by weight aqueous caustic (NaOH) solution (4.5 equivalents) and 50 mL of deionized (DI) water. The reaction solution was then kept at room temperature (22 °C). While maintaining the temperature, dinitrile (DN) was fed to the Hastelloy reactor at 2.4 mL / min. During the process, the internal temperature rose from 22°C to 27°C. During the DN supply, the agitation was set to 350 rpm. The nitrogen sparge was maintained at 2.5 L / min. The pH of the scrubber dropped from 8.38 to 1.50 during the addition. The temperature of the reactor mantle changed to 9.47. The reactor mantle temperature was set at 95°C for an additional 4 hours. 00 mL of DI water was added to make up for the loss of water (336.2 g of water was added to the knockout pot). During this charge hold time, the pH of the scrubber dropped from 9.47 to 10.0. The reaction mixture was held overnight at 85° C. with stirring without sparging. Reactor contents The mixture was heated to 95°C and the nitrogen sparge was set at 2.5 L / min. The second glycolonitrile was then added. 198 mL (1.53 mol) of 40 wt% glycolonitrile was charged into the ISCO The reaction mixture was added to the Parr reactor via a pump at 2 mL / min over 99 min. The temperature was held for an additional 4 hours. The final scrubber pH was 10.4. An additional 280 g of DI water was added to compensate for the loss of water. The reaction mixture was agitated with air at 1 L / min. The temperature (85° C.) was maintained overnight under sparging. After cooling, 474.0 g of final product was recovered. and analyzed (90% mass accountability).

[0049] Example 3: Preparation of EDTA: This was a laboratory-scale demonstration of the process of the present invention. g (0.62 mol) of a 63 wt% EDA / water mixture was placed in a 1 L jacketed reactor. The jacket temperature was set to 40°C. The agitation was set to 300 rpm. 129. 3 mL of a 40 wt% glycolonitrile solution (1.6 equiv., 1 mol) was pumped through an ISCO pump. The EDA was added via a 26-minute flow rate of 5 mL / min. The internal temperature of the reaction mixture was During the course of addition, the temperature rose from 35 to 39 °C. The reaction mixture was held at that temperature for an additional 60 min. The dinitrile reaction mixture at the end of the hold was colorless to pale yellow. In a 1 L Hastelloy C Parr reactor, 224.2 g (2.8 mol) of 50 wt. Aqueous caustic solution (4.5 eq.) and 50 mL of DI water were charged and then heated to 90° C. The DN solution was then fed into the Hastelloy C reactor at 1.9 mL / min. The agitation was set at 350 rpm and the nitrogen sparge was maintained at 1.0 L / min. The reactor temperature was then increased for an additional 4 The temperature was maintained at 90° C. for 1 hour. 100 mL of DI water was added during the hold to make up for water loss ( (110.8 g of water was collected in the knockout pot). The reaction mixture was stirred without sparging. The contents of the reactor were then heated to 90°C and the nitrogen sparge was turned on for 2. After setting the flow rate to 5 L / min, the second glycolonitrile was charged. 40% glycolonitrile (100 ml) was pumped via an ISCO pump at 2 mL / min over 99 min. The reaction mixture was held at temperature for an additional 4 hours. The pH of the clover was 10.28. An additional 500 g of DI water was added during the hold. The water loss was compensated for. The reaction mixture was kept at that temperature overnight under 1 L / min air sparge. After cooling, 589.0 g of final product was obtained and analyzed (92% mass accountability). ).

[0050] Example 4C: Comparative Preparation of EDTA This is a step similar to that used in previously known processes, where a very strong base is present from the very beginning of the process. This was a laboratory-scale demonstration. 35 g (0.58 mol) of EDA was added to a 1 L flask. The reactor was then charged with 209.7 g (2.62 moles) of 5 0 wt% aqueous caustic solution and 21.0 g water. Jacket temperature was set at 90° C. Agitation was set at 350 rpm. 305.8 mL of 40 wt. % glycolonitrile was added. The solution (2.36 mol) was reacted via an ISCO pump at 2 mL / min for 2.5 h. The internal temperature of the reaction mixture was maintained at 90° C. during the addition. Nitrogen was sparged through the reaction mixture at a rate of 1 L / min when 1 / 3 of the nitrile was added. The reaction mixture is held at temperature for an additional 4 hours to ensure complete conversion and then sparged. The mixture was held at 85°C overnight without any further rinsing. The final scrubber pH was 10.05. An additional 570 g of DI water was added to make up for the loss of water. After cooling, the final weight was 592.6 g. The product was removed from the reactor and analyzed (94% mass accountability).

[0051] Comparative Example 5C: Comparative Preparation of EDTA This is a step similar to that used in previously known processes, where a very strong base is present from the very beginning of the process. This was a laboratory-scale demonstration. A 1 L round-bottom flask was placed under the liquid. The system is equipped with a glass frit gas sparger, a water-cooled condenser, an overhead stirrer, and an addition funnel. The reactor was connected to a water scrubber that was acidified with acetic acid. After assembly, the 1 L reactor contained 11 Charged with 3.1g of 50% by weight sodium hydroxide and 20.14g of ethylenediamine The reaction was warmed to 95° C., then 195 g of 40 wt. % aqueous glycolonitrile was added to the reaction mixture. The reaction solution was added over a period of 10 minutes. The maximum temperature reached was 96°C. The pH of the scrubber was 4.38. The pH increased from 1.0 to 10.21. Some solids were observed to form on the walls of the 1 L reactor. This was dissolved in the reaction solution by adding 60.5 g of water. The solution was heated to 95°C for 1 The mixture was stirred at 05°C for 2.5 hours, then cooled and 316.3 g of the reaction solution was removed. The results are shown in Table 1.

[0052] Example 6C: Comparative Preparation of EDTA This is a step similar to that used in previously known processes, where a very strong base is present from the very beginning of the process. This was a laboratory-scale demonstration. A 1 L round-bottom flask was placed under the liquid. The system is equipped with a glass frit gas sparger, a water-cooled condenser, an overhead stirrer, and an addition funnel. The reactor was connected to a water scrubber (acidified with acetic acid). 50% by weight sodium hydroxide, 6.8 g water, and 21.15 g ethylenediamine The reactor was then warmed to 80° C. After reaching 80° C., 206.9 g of 40 wt. % aqueous glycolonitrile was added by continuous addition over 91 minutes. The temperature was 86° C. During the feed, the reaction solution was passed through a water scrubber, and the emptying rate was 2.5 L / min. The air stream bubbled. The pH of the scrubber increased from 5.42 to 10.28. The solution was diluted with 95% water. The mixture was stirred at .degree. C. overnight, then cooled and 319.4 g of reaction solution was removed.

[0053] Example 7: Preparation of EDTA This was a laboratory-scale demonstration of the process of the present invention. The bottom flask was equipped with a water-cooled condenser, an overhead stirrer, and an addition funnel. The system was placed under a nitrogen atmosphere. The reactor was charged with 97.5 g of 40 wt. % aqueous glycololine. The mixture was charged with 100 ml of tolyl and then cooled to 2° C. Ethylenediamine (22.5 g) was then added over 55 min. The maximum temperature reached during the feed was 9°C. The addition funnel was placed at 16.5°C. g of water was rinsed into the 1 L reactor and then fed into the reactor. The solution was allowed to warm to ambient temperature and then Transferred to the addition funnel along with 19 g of water. Add 140.7 g of 50 wt. % aqueous Sodium hydroxide was charged. The reaction solution was passed through an acidified (acetic acid) water scrubber, but 2. A stream of nitrogen at 5 L / min was bubbled in. The solution in the 1 L reactor was warmed to 36° C. Then, in the addition funnel The solution was added to a 1 L reactor over 135 minutes and the reaction temperature was increased from 36°C to 44°C. After the solution was dispensed from the funnel, water (33 grams) was added to the funnel to rinse down the sides. and then added to the 1 L reactor. The pH of the scrubber increased from 4.08 to 9.25. The solution was stirred at 40° C. overnight and then warmed to 95° C. Next, 128.8 g of 40 wt. of aqueous glycolonitrile was added over a period of approximately 3 hours. A nitrogen sparge was used to purify the air for the addition. The pH of the scrubber increased to 10.48. It was held at 95°C for an additional 2 hours. After that, the solution was cooled and taken out to obtain 397.2 g of a reaction solution.

[0054] Example 8: Preparation of EDTA This was a laboratory-scale demonstration of the process of the present invention. The bottom flask was equipped with a water-cooled condenser, an overhead stirrer, and an addition funnel. The reaction flask was charged with 168.5 g of 40 wt. % aqueous glycolonitrile and then cooled in an ice bath. The addition funnel was charged with 39.2 g of ethylenediamine. EDA was added to a 1 L flask so that the temperature was 12°C. The solution was warmed to 40°C and then 35.2 g of 50 wt. % aqueous sodium hydroxide was charged. The gas was sent to an acidified (acetic acid) water scrubber to capture ammonia, but the scrubber was operated at 2.5 L / min. The maximum temperature reached during the supply was 48°C. During this time, the scrubber The pH also increased from 4.06 to 9.82. The solution was stirred at 40° C. overnight and then cooled to 85° C. After reaching 85°C, 214.4 g of 40 wt% aqueous The glycolonitrile was added over a period of approximately 2 hours. After being held at 95° C. overnight, the solution was cooled. After removal, 649.2 g of a reaction solution was obtained.

[0055] Example 9: Preparation of EDTA This was a laboratory-scale demonstration of the process of the present invention.137. 4 mL (1.06 mol) of 40 wt% aqueous glycolonitrile solution was placed in a 1 L jacketed A glass reactor was loaded. The jacket temperature was set at 0° C. Agitation was set at 300 rpm. 59.5 g (0.62 mol) of a 63 wt% EDA / water mixture was added over a period of approximately 1 hour. The GN was added at 1 mL / min via an ISCO pump. The internal temperature of the reaction mixture was The reaction mixture was kept at 10°C for an additional 6 hours to ensure complete conversion. The dinitrile reaction mixture at the end of the hold was colorless to pale yellow. , the dinitrile was dissolved in 224.2 g (2.8 moles) of 50% by weight aqueous caustic solution (4.5 equivalents) and 60 mL of DI water was transferred to a 1 L jacketed reactor pre-charged with The reaction temperature was maintained at 40° C. (1.9 mL / min) during the reaction. The stirring was increased to 35° C. for the duration of the reaction. The rpm was set at 0.0. Air sparging was maintained at 2.0 L / min throughout the addition. The temperature was maintained at 40° C. for an additional 8-10 hours using air sparging. After an additional 4 hours of distillation at 95°C-100°C with 1.0 mL / min air sparge, the first The column was charged with 189.9 mL (1.46 mol) of 40 wt. % glycolonitrile. Coronitrile was added to the reactor via an ISCO pump at 1 mL / min over 190 min. The reaction mixture was kept at 85°C for an additional 8 hours under 1 L / min air sparge. The pH of the scrubber was 8.15. An additional 600 g of DI water was added during the hold. The water loss was compensated for. After cooling, 577.2 g of final product was analyzed (86% mass account intability).

[0056] Example 10: Test results. The products from Examples 1, 5C, 6C, 7, and 8 were analyzed. The following compounds were detected: The following compounds have been reported: EDTA, NTA, SEDDA (symmetric ethylenediamine-N-N'-diamine) Acetic acid = DA), UEDDA (unsymmetric ethylenediamine-N-N'-diacetic acid), and ED 3A (Ethylenediaminetriacetic acid). The results were as follows. The amounts shown are: Weight percentages are based on the total weight of the final product. [Table 2]

[0057] All of the examples show relatively good productivity for making EDTA, demonstrating the effectiveness of the present invention. The examples had lower NTA than the comparative examples.

[0058] The above laboratory scale example is based on a comparative method of making EDTA. The changes to the process of the invention result in comparable yields of EDTA and reduced production of NTA. These results are believed to be evidence that the same comparisons could be made on a larger scale (e.g., production regulation). This suggests that a significant reduction in NTA formation would be achieved if the That is, the NTA generated by the large-scale operation of the method of the present invention is comparable to the large-scale operation of the comparative method. It is expected that this will be less than the NTA produced in the work.

Claims

1. 1. A method for making ethylenediaminetetraacetic acid (EDTA), comprising: (a) A reaction mixture containing ethylenediamine (EDA) and glycolonitrile (GN). Providing a reaction mixture (a), the reaction mixture (a) comprising, based on the weight of the reaction mixture (a), Based on this, 0% by weight to 0.1% by weight of any compound having a pKa (PKaH) of the conjugate acid of 13 or more providing a base comprising (b) causing or allowing the reaction mixture (a) to react to form a compound of Structure D forming a dinitrile compound having N; 【Chemistry 1】 (c) contacting said DN with an aqueous solution of a base having a pKaH of 11 or greater; causing or allowing the compound to react to form a diacid compound having the structure DA. forming a 【Chemistry 2】 wherein each -R has the structure: 【Chemistry 3】 wherein each M is independently hydrogen, or an alkali metal, or a mixture thereof. , forming a (d) causing the DA to react sequentially or simultaneously with additional GN; or or allowing to form product (Pd); (e) Cause the product (Pd) to react with a base having a pKaH of 11 or greater.

20. The method of claim 19, further comprising the step of:

2. The reaction mixture (a) may further comprise any of the EDA used in step (a) optionally and placing the GN in a container in the form of an aqueous solution at E DA, which is 0-0.1% by weight based on the weight of DA, and then optionally GN.

2. The method of claim 1, wherein the aqueous solution is added to the container. 。

3. Reaction mixture (a) is formed by contacting an aqueous solution of EDA with an aqueous solution of GN. The method of claim 1 .

4. 2. The method of claim 1, wherein step (b) is carried out at a temperature of from 0° C. to 10° C.

5. 2. The method of claim 1, wherein in reaction mixture (a) the molar ratio of GN to EDA is 3:1 or less. How to.

6. At the end of step (e), the weight ratio of EDTA to nitrilotriacetic acid is 7:1 or greater. The method of claim 1 .

7. A composition comprising a compound having the structure DADN, 【Chemistry 4】 wherein each -R has the structure: 【Chemistry 5】 wherein each M is independently hydrogen, or an alkali metal, or a mixture thereof. , composition.

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