Process for the preparation of methoxylamine hydrochloride

Abstract

A process (100) and reactor assembly (200) for synthesis of methoxylamine hydrochloride (MAHCl) is disclosed. Methoxylamine hydrochloride is a key reagent for the preparation of one or more than one oxime derivative. The present disclosure relates to development of a process (100) for preparation of methoxylamine hydrochloride product by utilizing different reaction routes which minimizes the time consumption and is an economical process thereby minimizing the energy consumption of the overall process.

Description

[0001] Cross-reference and priority of related applications

[0002] This application claims priority to Indian Provisional Patent Application No. 202121005116, filed on February 5, 2021, and PCT Application No. PCT / IB2022 / 050854, filed on February 1, 2022, the contents of which are incorporated herein by reference. Technical Field

[0003] The subject matter described herein generally relates to methods for preparing methoxyamine hydrochloride. In particular, this subject matter relates to the preparation of high-yield solid methoxyamine hydrochloride and 30% to 40% methoxyamine hydrochloride solutions. Background Technology

[0004] Methoxyamine hydrochloride (hereinafter referred to as "MAHCl") is a major reagent used to prepare one or more oxime derivatives. Currently, traditional MAHCl preparation processes suffer from drawbacks such as low yield, large product loss, long processing time, low productivity, and high energy consumption.

[0005] Therefore, there has long been a need to develop an economical method to prepare methoxyamine hydrochloride products by utilizing different reaction routes, minimizing time consumption and thus minimizing the energy consumption of the entire process. Summary of the Invention

[0006] This invention is provided to introduce concepts related to the preparation method of methoxyamine hydrochloride (MAHCl). This invention is not intended to identify the essential features of the claimed subject matter, nor is it intended to define or limit the scope of the disclosed subject matter.

[0007] In one embodiment, a method for preparing methoxyamine hydrochloride is disclosed herein. The method for preparing methoxyamine hydrochloride may include various stages and sub-steps performed in multiple stages.

[0008] In one embodiment of the present application, the first stage can include the preparation of hydroxylamine disulfonate salt (hereinafter referred to as "HADS"). In the second stage, the process can include a methylation step of HADS. In the third stage of the process, the methylated HADS is subjected to hydrolysis to obtain methoxyamine sulfate. In the fourth stage, the process can include the recovery of methoxyamine base from methoxyamine sulfate under alkaline conditions. In the fifth stage, the process can include the conversion of methoxyamine base to obtain methoxyamine hydrochloride (MAHCl) by maintaining predetermined conditions. In the sixth stage, the process can include the concentration of the crude reaction mass of methoxyamine hydrochloride (MAHCl) to obtain a concentrated crude liquid mass of methoxyamine hydrochloride (MAHCl). In the seventh stage, the process can include the solidification and crystallization of a predetermined amount of methoxyamine hydrochloride (MAHCl) in the form of a concentrated liquid to obtain the final product of solid methoxyamine hydrochloride (MAHCl).

[0009] Abbreviations

[0010] HADS - Hydroxylamine disulfonate disodium salt

[0011] MADS - Methyl hydroxylamine disulfonate disodium salt

[0012] MAS - Methoxyamine sulfate

[0013] NODi - N, O-Dimethylhydroxylamine; N, O-dimethylhydroxylamine

[0014] MA Base - Methoxyamine base

[0015] MAHCl - Methoxyamine hydrochloride

[0016] DMS - Dimethyl sulfate

[0017] CSL - Caustic soda solution (sodium hydroxide)

[0018] DM water - Deionized water

[0019] BRIEF DESCRIPTION OF DRAWINGS

[0020] The detailed description will refer to drawings. In the drawings, the left-most digit of a reference number identifies the first figure in which this reference number appears. The use of the same reference numbers in different figures indicates similar and / or like components in the figures.

[0021] Figure 1 A process (100) for preparing crude methoxyamine hydrochloride according to an embodiment of the present subject matter is described.

[0022] Figures 2(a) to 2(f) A reaction assembly (200) for preparing crude methoxyamine hydrochloride according to an embodiment of the present subject matter is described.

[0023] Figure 2(a) depicts the reaction tank (201, 202) of the reaction assembly (200) for the preparation of basic HADS at a stable basic pH, according to an embodiment of the present subject matter.

[0024] Figure 2(b) depicts the reaction tank (203) of the reaction assembly (200) for the methylation of basic HADS, according to an embodiment of the present subject matter.

[0025] Figure 2(c) depicts the reaction tank (204) of the reaction assembly (200) for basic distillation and removal of O, N-dimethylhydroxylamine; N, O-dimethylhydroxylamine (NODi) impurities from MADS liquor, according to an embodiment of the present subject matter.

[0026] Figure 2(d) depicts the reaction tank (205) of the reaction assembly (200) for acid hydrolysis and acid distillation of MADS, according to an embodiment of the present subject matter.

[0027] Figure 2(e) depicts the reaction tank (206) of the reaction assembly (200) for the recovery of methoxylamine base, according to an embodiment of the present subject matter, by using a vacuum jet pump.

[0028] Figure 2(f) depicts the reaction tank (207) of the reaction assembly (200) for obtaining crude methoxylamine hydrochloride, according to an embodiment of the present subject matter.

[0029] Figure 3 Stage A of preparing (101) basic hydroxylamine disulfonic acid disodium salt (i.e. HADS) is described, according to an embodiment of the present subject matter.

[0030] Figure 4 Stage B of methylation (102) of basic hydroxylamine disulfonic acid salt (HADS) to obtain methyloxylamine disulfonic acid disodium salt liquor (MADS) is described, according to an embodiment of the present subject matter.

[0031] Figure 5 Stage C of acid hydrolysis (104) of MADS liquor to obtain acid hydrolyzed methoxylamine sulfate (MAS) is described, according to an embodiment of the present subject matter.

[0032] Figure 6 Stage D of recovering (106) methoxylamine base to obtain methoxylamine base is described, according to an embodiment of the present subject matter. DETAILED DESCRIPTION

[0033] Throughout this specification, the use of the expressions “various embodiments,” “some embodiments,” “one embodiment,” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in various embodiments,” “in some embodiments,” “in one embodiment,” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics can be combined in any suitable manner in one or more embodiments.

[0034] The words “comprise,” “have,” “contain,” and “include,” and other forms thereof, have the same meaning and are open-ended, as any one of the items listed after the word complies with the same, also does not mean that only the listed items are included, but also means that only the listed items are limited.

[0035] It must also be noted that the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Although any methods similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, exemplary methods are described. The disclosed embodiments are merely examples of the present disclosure, which can be embodied in various forms.

[0036] Various modifications to the embodiments can be apparent to those skilled in the art, and the generic principles defined herein can be applied to other embodiments. However, it is to be understood that the disclosure is not intended to be limited to the

[0037] In one embodiment of the present application, reference is made to Figure 1 A process (100) for preparing crude methoxylamine hydrochloride is illustrated in accordance with an embodiment of the present application. The process (100) for preparing methoxylamine hydrochloride includes multiple steps and is further divided into seven stages.

[0038] In one embodiment of the present application, the first stage can include preparation of basic hydroxylamine disulfonic acid disodium salt (i.e. HADS). In the second stage, the process (100) can include methylation of basic HADS to obtain methyl hydroxylamine disulfonic acid disodium salt (MADS). In the third stage, acid hydrolysis of methylated HADS (MADS) can be carried out to obtain methoxylamine sulfate. In the fourth stage, recovery of methoxylamine base can be carried out in the presence of caustic soda solution (NaOH) to remove the sulfate moiety and obtain methoxylamine. In the fifth stage, the process (100) can include obtaining crude methoxylamine hydrochloride in the presence of hydrochloric acid (HCl) to obtain crude methoxylamine hydrochloride product (hereinafter also referred to as methoxylamine HC1 or MAHC1) by maintaining predetermined conditions. In the sixth stage, the process (100) can include concentrating the crude reaction mass of methoxylamine hydrochloride (MAHC1) to obtain concentrated crude liquid mass of methoxylamine hydrochloride (MAHC1). In the seventh stage, the process can include solidifying and crystallizing (109) the predetermined amount of methoxylamine hydrochloride (MAHC1) in the form of concentrated liquid to obtain the final product of solid methoxylamine hydrochloride (MAHC1).

[0039] First stage (Stage A) of preparation (101) of basic HADS

[0040] In one embodiment of the present application, the process (100) can include preparation (101) of basic hydroxylamine disulfonic acid disodium salt (hereinafter simply referred to as “HADS”) in stage (A). The HADS preparation (101) stage (A) can include an initial step of preparation of purified crystalline sodium nitrite (NaNCb). In an embodiment of the present application, the purified crystalline sodium nitrite (NaNCb) is obtained in an improved form with minimum impurities based on the disclosure of Indian Application No. 201921047080 titled “Aventuri-air ammonia mixer enabled for two burner system” filed on November 19, 2019 and Indian Application No. 201921004836 titled “Apparatus and process for conversion of ammonia sodium nitrite” filed on February 7, 2019, which are incorporated herein by reference.

[0041] In one embodiment, in the first stage of preparation (101) of HADS, the external physico-chemical conditions of the reactor assembly (200) are adjusted. In one embodiment, the adjustment of the external conditions of the reactor assembly can include maintaining the cooling water pressure of the water sprayers to not more than 1.5 kg / cm 2 In the next step, the heating steam temperature of the reactor assembly (200) is adjusted to not more than 2.0 kg / cm 2In the next step, one or more reaction components can be added to one or more reaction tanks of the reactor assembly (200).

[0042] Referring to Fig. 2(a) and Figure 3 According to one embodiment of the present application, the preparation (101) of basic HADS (Stage A) is illustrated.

[0043] In one embodiment, the step of adding (301) one or more reactants such as sodium nitrite (NaNCb) and caustic soda solution (NaOH) can be carried out wherein water can be fed to the overflow limit of the reaction tank (201) by pumping technique to obtain a premix of sodium nitrite (NaNCb) and caustic soda solution (NaOH). The ratio of the premix of sodium nitrite (NaNCb) and caustic soda solution (NaOH) can be maintained as 1:1. In one embodiment, the concentration of caustic soda solution (NaOH) can be maintained at 47.3% w / w to 49% w / w. In one embodiment, a predetermined amount of sulfur dioxide (SO2) gas can be fed into the reaction tank (201).

[0044] In one embodiment, the method of preparing (101) basic HADS can further comprise the step of mixing (302) the premix of sodium nitrite (NaNCb) and sodium hydroxide (NaOH) while feeding SO2 gas to the reaction tank (201) for continuous preparation of acidic HADS. In one embodiment, the step of mixing (302) the premix of sodium nitrite (NaNCb) and sodium hydroxide (NaOH) while feeding SO2 gas to the reaction tank (201) can be carried out by using a predetermined stirrer speed in a circular motion to obtain a basic hydroxylamine disulfonate (HADS) solution in the reaction tank (201). In one embodiment, for a small scale reactor (which can be 3 kl), a huge power value of 20 to 29 can be maintained by being able to stir vigorously at a circulation rate of almost 30 to 50 times the volume. In one embodiment, the pH of the reaction mixture can be maintained at 2 to 5, more preferably at a stable pH value of 2.8. In one embodiment, 12% to 18% of acidic HADS can be obtained.

[0045] In another embodiment, the acidic HADS having a concentration of 12 wt / vol% to 18 wt / vol% and a stable pH of 2.8 to 5 can be further transferred to the reaction tank (202) of the reactor assembly (200) by an overflow technique. In the reaction tank (202), a step of reacting (303) the acidic HADS with a lye (NaOH) can be carried out to obtain the basic HADS. In an embodiment, the pH of the reaction tank (202) can be maintained at about 9 to 13, preferably about 11. In an embodiment, the preparation (101) of the basic HADS process is carried out as a continuous process at a stable basic pH of 9 to 12 and preferably 11. In an embodiment, the method implemented in stage (A) can result in an increase of at least 5% in the overall yield of the basic HADS. This increase is felt due to an increase in the amount of water to maintain the previous concentration. In one example, the amount of water is increased from 60 liters previously to 120 liters. This is due to the fact that the traditional batch process avoids decomposition as compared to the continuous process.

[0046] Methylation (102) of basic HADS to obtain MADS - second stage (Stage B)

[0047] Referring to Figure 1 In another embodiment of the present application, the method (100) can include a second stage (B) of methylation (102) of the basic HADS to obtain the methoxylated hydroxylamine disulfonic acid disodium salt (hereinafter referred to as "methoxylated HADS" or "MADS").

[0048] Referring to FIG. 2(a), FIG. 2(b) and Figure 4 In accordance with an embodiment of the present application, the second stage (B) of methylation (102) of the basic HADS to obtain the MADS is illustrated.

[0049] The second stage (B) of methylation (102) of the basic HADS can also include charging (401) the basic HADS from the reaction tank (202) in the reaction tank (203) of the reactor assembly (200). In an embodiment, the basic HADS can be fed to the reaction tank (203) by a gravity filling technique in a continuous process.

[0050] In an embodiment of the present application, the methylation (102) of the basic HADS can also include heating (402) the basic HADS in the reaction tank (203) to a temperature of 60°C to 80°C, preferably 65°C to 72°C, more preferably 70°C. In an embodiment, the heating step is carried out with the help of a steam jacket heating technique.

[0051] In an embodiment of the present application, the methylation (102) of alkaline HADS can further comprise a step of maintaining (403) a predetermined pH level by mixing the caustic soda liquor (NaOH) fed from the storage tank with the alkaline HADS in the reaction tank (203). In an embodiment, the pH level can be maintained at 9 to 12.

[0052] In an embodiment, the reaction tank (203) can be used as a stirred tank (203b) wherein the stirred tank (203b) can be kept in a circulating motion for proper mixing with the caustic soda liquor (NaOH) while feeding the caustic soda liquor (NaOH) into the reaction tank (203a) comprising the alkaline HADS. In an embodiment, the time period for mixing one or more components in the reaction tank (203) can be maintained at 30 minutes to 2 hours, preferably 1 hour.

[0053] In an embodiment of the present application, the methylation step (102) can comprise a step of reacting (404) dimethyl sulfate (DMS) (95.0% to 99.0% w / w) continuously added from the storage tank with the pre-mix of caustic soda liquor (NaOH) and alkaline HADS having a predetermined alkaline pH level (as mentioned above) in the reaction tank (203) for a predetermined time period of 4 hours to 6 hours depending on the batch size and temperature range of 62°C to 75°C. In an embodiment, the accurate amount of dimethyl sulfate (DMS) can be continuously added to the stirred tank (203) at a 0.80 ± 1 mole ratio in phase B or in the methylation (102) step of alkaline HADS. Here, the yield improvement of MADS and time reduction to 1 hour, thereby reducing the maintenance time from 5 hours to 4 hours) is achieved by making the process semi-continuous by batch addition in the conventional technology.

[0054] In yet another embodiment, the temperature of the reaction tank (203) can be maintained at about 72°C ± 10°C, more preferably 65°C to 68°C by regulating the heating and cooling jolt mechanism of the steam jacket before feeding the caustic soda liquor (NaOH) into the reaction tank (203) while charging dimethyl sulfate (DMS) into the reaction tank (203). The heating and cooling jolt mechanism is achieved by simultaneous operation of heating and cooling cycles to maintain the temperature. In an embodiment, the reaction time of 95.0% to 99.0% of dimethyl sulfate (DMS) with the pre-mix of caustic soda liquor (NaOH) and alkaline HADS can be adjusted at 2 hours to 5 hours, preferably about 2.5 hours.

[0055] In yet another embodiment, optionally, another batch of caustic soda liquor (NaOH) can be charged into the reaction tank (203) to maintain the alkaline pH of the reaction mixture comprising basic HADS, dimethyl sulfate (DMS) and caustic soda liquor (NaOH) to obtain higher yield of methylated HADS.

[0056] In an embodiment, the addition of a predetermined amount of caustic soda liquor (NaOH) and a predetermined amount of dimethyl sulfate (DMS) (molar ratio of 0.8:0.9 moles of DMS based on the sodium nitrite added) can be to achieve a stable alkaline pH level of 10.5 by continuous addition of two components comprising caustic soda liquor (NaOH) and dimethyl sulfate (DMS) and to obtain improved yield of methylated HADS i.e. methoxylamine disulfonic acid disodium salt (MADS) liquor. In yet another embodiment, simultaneous and continuous addition of caustic soda liquor (NaOH) and dimethyl sulfate (DMS) can result in reduction of total digestion time of the reaction mixture by maximum 2.5 hours to 4 hours.

[0057] In an embodiment, the methoxylamine disulfonic acid disodium salt (hereinafter can also be referred to as “MADS”) liquor can comprise a certain amount of free alkaline component i.e. caustic soda liquor (NaOH). In an embodiment, the percentage of free alkaline substance is about 0.5% to 4%. The MADS liquor comprising a small amount of free alkaline component can be further transferred to the reaction tank (204) for carrying out third stage of hydrolysis of (MADS) liquor to obtain acid hydrolyzed methoxyamine sulfate (hereinafter can also be referred to as “MAS”).

[0058] Third stage (Stage C) of acid hydrolysis (104) of MADS solution to obtain acid hydrolyzed methoxyamine sulphate (MAS)

[0059] In yet another embodiment of the present application, the process (100) can comprise a third stage (C) of acid hydrolysis (104) of MADS liquor to obtain acid hydrolyzed methoxyamine sulfate (MAS).

[0060] Referring to FIG. 2(b), FIG. 2(c) and FIG. 2(d) of the reactor assembly (200) and Figure 5 , the third stage (C) of acid hydrolysis of MADS liquor to obtain acid hydrolyzed MAS is explained in accordance with an embodiment of the present application.

[0061] The third stage C of acid hydrolysis (104) of MAD liquor can comprise transferring (501) the MADS liquor comprising a predetermined amount of free alkaline component from the reaction tank (203) into the reaction tank (204) of the reactor assembly (200). In an embodiment, the MADS liquor can be transferred (501) into the reaction tank (204) by gravity feeding technique for acid hydrolysis and conversion of MADS liquor into acid hydrolyzed methoxyamine sulfate (MAS).

[0062] In yet another embodiment, optionally, excess caustic liquor (NaOH) can be added to the reaction tank (204) to maintain the basic pH and free alkali content of the reaction mixture comprising MADS liquor. In yet another embodiment, the free alkali content (free NaOH) of the MADS liquor can be maintained at about 1.3% to effectively complete the basic distillation and the entire acid hydrolysis process under basic conditions and to reduce the formation of N-dimethyl hydroxylamine, N,0-dimethyl hydroxylamine (NODi) impurities in stage 3.

[0063] In one embodiment, when the free alkali percentage of the MADS liquor is observed to be less than 1.3%, then optionally, an additional amount of caustic liquor (NaOH) is intermittently added to the reaction tank (204).

[0064] Basic distillation

[0065] Referring to Fig. 2(c), in one embodiment of the present application, the method (100) can comprise the step of subjecting the MADS liquor to basic distillation at a temperature in the range of 100°C to 113°C to recover (105) basic water. In one embodiment, in the step of basic distillation, the reaction mass is subjected to steam jacket heating technique at a temperature in the range of 100°C to 113°C.

[0066] In another embodiment of the present application, the method (100) can comprise the step of recovering (105) basic water from the MADS liquor by using two or more heat exchangers to remove the basic water and unknown impurities such as O,N-dimethyl hydroxylamine; N,0-dimethyl hydroxylamine (NODi) impurities from the reaction tank (204) and to obtain impurity free MADS. In one embodiment, the basic water is further transferred to a waste water treatment plant for further purification treatment as per standard waste water treatment guidelines.

[0067] In one embodiment, by using the continuous process as described in stage A and stage B, a reduction in the amount of water distillation by at least 60% to 65% is achieved in the step of recovering basic water by basic distillation of the MADS liquor. In one embodiment, the impurity free MADS is transferred to the reaction tank (205) for acid distillation of the MADS and to obtain methoxyamine sulphate (MAS) product. In this step, the improvement is achieved by conducting a negative experiment for the required water removal and determining the appropriate amount which is at least reduced by 60% to 65% to reduce the time period to 3 hours to 4 hours. In one example, the draw of basic water can be varied from zero to the maximum level, which gives a benchmark figure of reduction from 900 kg to 240 kg by calculating the end to end results.

[0068] Acid distillation

[0069] Referring to Fig. 2(d), in an embodiment of the present application, the method (100) can comprise the step of cooling (502) the impurity free MADS to a temperature in the range of 55°C to 60°C in the reaction vessel (205). In an embodiment, the impurity free MADS can be cooled (502) from 113°C to a temperature in the range of about 55°C to 60°C by using steam jacket cooling.

[0070] In an embodiment, the step of slow addition (503) of H2SO4 can be performed to adjust the predetermined acidic pH when the reactant mass is cooled to the predetermined range of 55°C to 60°C.

[0071] In the next step, the acidic distillation (504) of the impurity free MADS can be carried out to obtain methoxyamine sulphate (MAS). In an embodiment of the present application, the method (100) can comprise the step of acidic distillation (504) by gradually increasing the temperature to reach the total reflux condition and to obtain the methoxyamine sulphate (MAS) product. In an embodiment, the pH of the reactant mass comprising MADS and concentrated H2SO4 is maintained to be highly acidic, i.e. at a level of pH 2 to 6 to carry out the acid hydrolysis. In an embodiment, the gradual increase in temperature to 113°C is achieved by heating the reactant mass comprising MADS and concentrated H2SO4 to reach the total reflux condition for a time period of 1 hour to obtain the methoxyamine sulphate (MAS).

[0072] In an embodiment, the recovery (105) of the acidic water from the reactant mass can be carried out by using the acid reflux method and the acidic water can also be transferred to the effluent treatment unit for further purification process as per the standard effluent treatment guidelines. In an embodiment, the methoxyamine sulphate (MAS) can also be transferred to the reaction vessel (206) to basify the MAS and obtain the methoxyamine base product.

[0073] Fourth stage (Stage D) of recovery of methoxyamine base 106) to obtain methoxyamine base (Stage D) Figure 6

[0074] In another embodiment of the present application, the method (100) can comprise the fourth stage of recovery (106) of the methoxyamine base in the presence of caustic soda solution (NaOH) to remove the sulphate moiety and to obtain the methoxyamine base (hereinafter can be referred to as “methoxy amine” or “MA base”).

[0075] Referring to Fig. 2(e) and Fifth stage (Stage E) of acidification (107) of methoxyamine base and obtaining of crude methoxyamine hydrochloride The recovery (106) of the methoxyamine base from the methoxyamine sulphate (MAS) to obtain the methoxyamine base can be carried out in the reaction vessel (206).

[0076] In an embodiment of the present application, the fourth stage of recovery of methoxy base of methoxyamine sulphate (MAS) (106) can be carried out at a cooling temperature of 40°C to 45°C by adding (602) caustic soda liquor (NaOH) from a storage tank. In an embodiment, the addition (602) of caustic soda liquor (NaOH) to the reaction tank (206) containing methoxyamine sulphate (MAS) can be carried out by partial addition technique.

[0077] In an embodiment, the reaction tank (206) can be an ejector reactor. In this process, the normal pressure distillation of the active ingredient (MAB) is converted into vacuum distillation using special materials suitable for the structure of the ejector in highly corrosive environments (such as PTFE, PFA, ETPFA, PVRC, special PP, etc.), thus reducing the loss of active ingredient (MAF) whose boiling point is very low, below 50°C. The ejector system is a combination of ejectors whose design aims to generate the required vacuum to carry the active ingredient gas (MAB) and mix it with the circulating HC1 solution by generating the effect of a 4m to 5m packed column. The ejector reactor (206) can be configured to carry out the basification reaction and distillation of the methylamine base (MAB). In an embodiment, at this stage, the pH level of the reaction mass containing the methoxyamine base can be maintained at 7 to 9.

[0078] In another embodiment, the basification step can include cooling (601) the reaction mass containing methoxyamine sulphate to a temperature of 40°C to 45°C, after which a predetermined amount of caustic soda liquor (NaOH) can be gradually added to the reaction mixture to obtain the methoxyamine base intermediate product. At this time, the temperature of the reaction mass is preferably maintained below 60°C.

[0079] In an embodiment, the reaction tank (206) can include a vacuum ejector pump configured for recovery of methoxyamine base. In an embodiment, the vacuum range of the vacuum ejector pump is maintained at 630mmHg to 670mmHg. In an embodiment, the vacuum level should be maintained with a variation of ± 5%. In an embodiment, the operating conditions of the vacuum ejector pump can be maintained such that the pump discharge pressure is maintained at 2.5 Kg / cm 2 to 3.5 Kg / cm 2 and the vacuum range is maintained between (630mmHg to 670mmHg). The vacuum pump is at about 700mmHg.

[0080] Concentration (108) of crude reaction mass of methoxyamine hydrochloride (MAHC1) to obtain concentrated liquid mass of methoxyamine hydrochloride (MAHC1)

[0081] In another embodiment of the present application, the process (100) can include a fifth stage of obtaining the crude methoxylamine hydrochloride (E) in the presence of hydrochloric acid (HC1) to obtain crude methoxylamine hydrochloride product (hereinafter referred to as "methoxylamine.HC1" or "MAHC1").

[0082] In one embodiment, the step of recovering (106) the methoxylamine base from the ejector reactor (206) can be performed using a vacuum ejector pump. The methoxylamine base recovered from the ejector reactor (206) can be further transferred to the reaction tank (207) containing hydrochloric acid (HC1) for reaction with the hydrochloric acid (HC1) and synthesis of crude methoxylamine hydrochloride (MAHC1) product.

[0083] Referring to Figure 2(f) of the reactor assembly (200), a predetermined amount of HC1 can be added in the reaction tank (207). In one embodiment, at this stage, the reaction mass of methoxylamine base can be added to the reaction tank (207) containing HC1. The pH level of the reaction mass containing methoxylamine base and HC1 can be maintained at 8.3 to 8.5. In another embodiment, the temperature of the methoxylamine base can be cooled to 20°C to 25°C by applying the cooling jacket technology.

[0084] In one embodiment of the present application, the acidification (107) step of the methoxylamine base is performed by reacting the methoxylamine base with concentrated HC1 at a temperature of 20°C to 25°C in the reaction tank (207) to obtain crude methoxylamine hydrochloride.

[0085] In one embodiment, an additional predetermined amount of cold HC1 at a temperature of 25°C to 20°C can be added to the reaction mixture containing the methoxylamine base to obtain the desired crude methoxylamine amine hydrochloride (MAHC1) product.

[0086] Sixth stage (Stage F) of solidification and crystallization (109) of a predetermined amount of methoxyamine hydrochloride (MAHC1) in the form of concentrated liquid to obtain a final product of solid methoxyamine hydrochloride (MAHC1) Seventh stage (Stage G)

[0087] In one embodiment of the present application, the stage (F) of concentrating (108) the crude reaction mass of methoxylamine hydrochloride (MAHC1) can be performed in the reaction tank (207) to obtain the concentrated crude liquid mass of methoxylamine hydrochloride (MAHC1) by recovering the methoxylamine base.

[0088] In another embodiment of the present disclosure, a process for obtaining methoxylamine hydrochloride (MAHCl) in solid and liquid concentrated forms is disclosed. In the first step, crude methoxylamine hydrochloride (MAHCl) liquid can be heated to a temperature of 55°C to 60°C by a reboiler to evaporate excess liquid material from the crude liquid material of methoxylamine hydrochloride (MAHCl) and obtain a concentrated liquid form of methoxylamine hydrochloride (MAHCl) solution of 30% to 40%.

[0089] ​ ​

[0090] In the next optional stage (G), solidification and crystallization (109) of a predetermined amount of concentrated liquid form of methoxylamine hydrochloride (MAHCl) can be carried out to obtain a final product of solid methoxylamine hydrochloride (MAHCl).

[0091] In an alternative embodiment, methoxylamine hydrochloride solid is obtained in stage G of solidification and crystallization (109) of methoxylamine hydrochloride (MAHCl).

[0092] In another embodiment of the present disclosure, methoxylamine hydrochloride (MAHCL) obtained according to the present invention can be white or pale yellow crystals, easily soluble in water, soluble in ethanol.

[0093] In another embodiment of the present disclosure, methoxylamine hydrochloride (MAHCL) obtained according to the present invention can be used to produce antibiotic drugs and bactericides, such as cefuroxime axetil.

[0094] According to the embodiments of the present disclosure, the above-mentioned process for preparing methoxylamine hydrochloride (MAHCl) has the following advantages, including but not limited to:

[0095] The final yield of methoxylamine hydrochloride (MAHCl) is up to 49% to 50%.

[0096] The requirement for removing the amount of basic water in the basic distillation step is minimized.

[0097] The time and energy consumption of the entire process for obtaining methoxylamine hydrochloride (MAHCl) are reduced.

[0098] The following experimental section further describes the present invention:

[0099] The aforementioned paragraphs or embodiments, examples and alternatives of the specification and drawings, including any of their respective aspects or individual features, can be obtained independently or in any combination. Features described in connection with one embodiment apply to all embodiments, unless the features are incompatible.

Claims

1. A method for synthesizing methoxyamine hydrochloride (MAHCl), wherein the method comprises one or more stages: Stage A in the preparation of basic hydroxylamine disulfonic acid disodium salt (HADS) Stage A, which involves the preparation of basic hydroxylamine disulfonic acid disodium salt (HADS), includes the following steps: One or more reactants are added to a reaction vessel, comprising a premix of sodium nitrite (NaNO2), caustic soda solution (NaOH) and water, wherein water is pumped to the overflow limit of the reaction vessel to obtain the premix of sodium nitrite (NaNO2) and caustic soda solution (NaOH). A premix of sodium nitrite (NaNO2) and sodium hydroxide (NaOH) is mixed while SO2 gas is fed into the reaction vessel to continuously prepare disodium acid hydroxylamine disulfonate (HADS); and Acidic hydroxylamine disulfonate disodium salt (HADS) is reacted with caustic soda solution (NaOH) to obtain basic hydroxylamine disulfonate disodium salt (HADS); Stage B involves methylating basic hydroxylamine disulfonate disodium salt (HADS) in a reaction vessel to obtain methyl hydroxylamine disulfonate disodium salt (MADS) solution. Alkaline water is recovered from MADS solution in a reaction vessel using two or more heat exchangers. The recovery of alkaline water from MADS solution using two or more heat exchangers can remove alkaline water and other substances contained in the reaction vessel. N-dimethylhydroxylamine, N,O -Unknown impurity of dimethylhydroxylamine (NODi); Stage C involves acid hydrolysis of MADS solution to obtain acid-hydrolyzed methoxyamine sulfate (MAS). Acidic water is recovered from the reactants in a reaction vessel; Stage D involves recovering methoxyamine base in a reaction vessel in the presence of caustic soda solution (NaOH) to remove the sulfate fraction and obtain methoxyamine. Stage E involves acidifying the methoxyamine base recovered from the reaction vessel to a reaction vessel containing HCl to obtain crude reactants of methoxyamine hydrochloride (MAHCl). Stage F involves concentrating the crude reactant of methoxyamine hydrochloride (MAHCl) in a reaction vessel to obtain a concentrated crude liquid methoxyamine hydrochloride (MAFCl); and Stage G: Curing and crystallization of methoxyamine hydrochloride (MAHCl) to obtain solid methoxyamine hydrochloride.

2. The method according to claim 1, wherein sodium bisulfite and sodium nitrite react in a molar ratio of 1:2.2 to 10 to obtain basic hydroxylamine disulfonic acid disodium salt (HADS), and wherein the premix of sodium nitrite (NaNO2) and caustic soda solution (NaOH) is maintained in a 1:1 ratio.

3. The method according to claim 1, wherein stage B of methylating basic hydroxylamine disulfonate disodium salt (HADS) to obtain methyl hydroxylamine disulfonate disodium salt (MADS) solution comprises the following steps: The alkaline HADS is loaded from the reaction vessel into the reaction vessel of the reactor assembly; Heat alkaline HADS to a temperature of 60°C to 80°C; The predetermined pH level is maintained by mixing the caustic soda solution (NaOH) input from the storage tank with the alkaline HADS in the reaction tank. and A solution of disodium methyl hydroxylamine disulfonate (MADS) is obtained by reacting 95.0 to 99.0 wt% of dimethyl sulfate (DMS) added continuously from a storage tank with a premix of caustic soda solution (NaOH) and alkaline HADS.

4. The method of claim 1, wherein stage C, acid hydrolysis of MADS solution to obtain acid-hydrolyzed methoxyamine sulfate (MAS), comprises the following steps: The MADS solution containing a predetermined amount of free alkaline components is transferred from the reaction tank to the reaction tank of the reactor assembly; The impurity-free MADS was cooled to a temperature of 55°C to 60°C in the reaction vessel; Slowly add H2SO4 to adjust to the predetermined acidic pH; and Acid distillation is performed by gradually increasing the temperature to achieve total reflux conditions to obtain acid-hydrolyzed methoxyamine sulfate (MAS).

5. The method of claim 1, wherein stage D of recovering methoxyamine base comprises the following steps: Cool the reactants containing methoxyamine sulfate to a temperature of 40°C to 45°C; and Add caustic soda solution (NaOH) to a reaction vessel containing methoxyamine sulfate (MAS) to obtain a methoxyamine base intermediate.

6. The method according to claim 1, wherein the step of recovering methoxyamine base and alkalized methylated disodium hydroxyamine disulfonate (HADS) from methoxyamine sulfate under alkaline conditions is carried out in the presence of caustic soda solution (NaOH).

7. The method according to claim 1, wherein the acidification of the methoxyamine base is carried out in the presence of hydrochloric acid (HCl) via an ejector reactor to obtain methoxyamine hydrochloride (MAHCl) in a reaction vessel at a temperature of 20°C to 25°C.

8. The method of claim 1, wherein the concentration stage F comprises heating the crude liquid material of methoxyamine hydrochloride (MAHCl) to a temperature of 55°C to 60°C via a reboiler, wherein the reboiler is configured to evaporate excess liquid material from the crude liquid material of methoxyamine hydrochloride (MAHCl) and obtain a 30% to 40% methoxyamine hydrochloride (MAHCl) solution.

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