CN115298166A

CN115298166A - Process for preparing DTEA hydrochloride

Info

Publication number: CN115298166A
Application number: CN202080098560.9A
Authority: CN
Inventors: A·P·哈格; P·J·托马斯
Original assignee: Amsa GmbH
Current assignee: Amsa GmbH
Priority date: 2020-04-19
Filing date: 2020-04-19
Publication date: 2022-11-04
Also published as: EP4121412A4; CA3179998A1; WO2021216029A1; MX2022012786A; EP4121412A1; KR20230065194A

Abstract

The present invention provides an improved process for preparing DTEA hydrochloride from decene and cysteamine hydrochloride using a catalyst, solvent and co-solvent to aid the reaction and provide low temperature stability of the resulting product solution.

Description

Process for preparing DTEA hydrochloride

Technical Field

The present invention relates generally to an improved process for preparing DTEA hydrochloride from 1-decene and cysteamine hydrochloride (CA-HCl).

Background

Industrial chemicals are typically manufactured using solvent-based reaction processes, followed by isolation, purification, and packaging. Many such chemical products are then formulated into commercial products by mixing the active ingredients (AI; see glossary below for abbreviations and acronyms) with other materials optimized and specific for their end use. When formulated as an aqueous solution, the curing and/or AI precipitation problems often become a problem when the formulation is stored (or in some cases, even briefly subjected) to an environment below room temperature. Partial settling and settling of solids results in variations in AI concentration, as well as inaccurate and inefficient transfer of the formulation from the storage vessel to the end-use vessel. In applications where pumping or spraying of the formulation is required, solids may cause clogging of filters and/or nozzles. Thus, the ability to maintain a solids-free pumpable homogeneous material is critical to avoid expensive and inconvenient heating and stirring operations during formulation operations and use.

Description of the Related Art

Some patents disclose the use of additives in microbicidal formulations to improve low temperature stability (to prevent AI precipitation or formulation solidification). Some of these patents are provided below. None of the techniques listed below uses GLTS reagent (defined in the glossary below) as a co-solvent to perform the reaction to prepare DTEA hydrochloride.

U.S. published application 2008/0076803 (Beilfuss) describes the addition of one or more aromatic alcohols to a 1, 2-benzisothiazolin-3-one formulation to increase low temperature stability. In particular, preferred additives are selected from the group consisting of (i) aryloxyalkanols (glycol monoaryl ethers), (ii) arylalkanols, and (iii) oligoalkanol aryl ethers or mixtures thereof. The reference specifies the order of preparation of the formulation in claim 13, and it is clear that GLTS is the last component added and is not taught or used in any of the GLTS co-solvent processes of the reference.

WO2001/041570 (Beilfuss) describes the use of the same additive package as in US 2008/0076803 described above, but they are used to improve the stability and reduce inhomogeneity of different AI mixtures.

U.S. published application 2013/0217579 (Wacker) describes a novel cryogenic solvent for pesticide formulations comprising adding GLTS Propylene Glycol (PG) and glycerol to the formulation.

US 5,371,105 (Damo) describes novel aqueous formulations of agrochemically active substances which are sparingly soluble in water. These formulations are water-in-oil or oil-in-water emulsions. One additive of the formulation is GLTS, preferably glycerol, but also EG, PG and polyethylene glycol are mentioned.

US 5,369,118 (resillein) teaches the use of GLTS adjuvants to improve the stability of triazole fungicide formulations, thereby preventing solids formation in aqueous spray solutions and preventing nozzle and line filter clogging. PG and glycerol are preferred.

US 5,206,225 (Horstmann) teaches the use of GLTS adjuvants to improve the stability of triazole fungicide formulations, thereby preventing solids formation in aqueous spray solutions and preventing nozzle and line filter clogging. PG and glycerol are preferred.

U.S. Pat. No. 7,368,466 (Beilfuss) discloses water-based formulations containing certain GLTS fungicides, a carbendazim (carbendazim) salt, which exhibit long-lasting low temperature stability. Beilfuss et al cite Benzyl Alcohol (BA) as the preferred GLTS and 1-phenoxy-2-propanol (PP) as the particularly preferred GLTS; neither of these solvents is a satisfactory LTS co-solvent in the DTEA hydrochloride process described herein.

US 5,087,757 (Mariam) teaches the use of various solvents in the reaction of decene and CA HCl (2-aminoethanethiol hydrochloride, also known as cysteamine hydrochloride) using catalysts/initiators including hydrogen peroxide and azo initiators to produce DTEA hydrochloride. These solvents include glycols and glycol ethers, and mixtures thereof with water. Examples mentioned are: ethylene glycol; propylene glycol; propylene glycol methyl ether; dipropylene glycol methyl ether; diethylene glycol; triethylene glycol; tetraethylene glycol; and dipropylene glycol, preferably propylene glycol and tetraethylene glycol. Some of the disadvantages of using the Mariam reaction for the production of DTEA hydrochloride are: (1) The high conversion rate of reactants is difficult to realize, and the high conversion rate of the reactants to DTEA hydrochloride can be realized only by adding the catalyst for many times and prolonging the reaction time; (2) Dilution with the preferred solvent (water) will result in formulations with severe cure/solids formation problems at low temperatures (defined as about 32 ° F to about 60 ° F).

U.S. H1265 statutory invention registration (Brady) teaches various alcohol (hydroxyl group-containing) additives that can be added to the DTEA hydrochloride reaction product prepared by Mariam's process (using PG or tetraethylene glycol (TEG) as the reaction solvent). The Brady technique dilutes the reaction product mixture with BTS (defined in the glossary below) to provide low temperature stability. BTS solvents mentioned are butanol, cyclohexanol, hexanol, isobutanol, ethylene glycol phenyl ether (synonym for 2-Phenoxyethanol (PE)) and propylene glycol phenyl ether (synonym for 1-phenoxy-2-propanol (PP)) and mixtures thereof. Some of the disadvantages of using Brady's BTS with the products of these methods are: 1) Adding BTS to an organic solvent-based reaction mixture results in higher overall product costs; 2) The addition of additional organic chemicals to the formulation presents problems in the application of the product in industrial water treatment: the organic solvent in the formulation is a nutrient for microbial growth, making its control more challenging and more costly. The amount of organic solvent in the formulation should be minimized as much as possible. One major limitation of the extrapolation of Brady to other technical solutions is that the screening for low temperature stability is performed in particular for a DTEA hydrochloride solution consisting of (approximately) 45wt% DTEA, 45wt% pg, 7wt% water and 3wt% impurities. Although PG is not the LTS of this formulation, PG is a better solvent for DTEA hydrochloride than water. The results of the Brady study did not correlate well with other PG-free DTEA hydrochloride formulations.

US 5,025,038 (Relenyi) describes an ETOX process for preparing DTEA hydrochloride using PG as a solvent to provide low temperature stability; however, this method has similar solidification/solid formation problems at low temperatures as Mariam does.

Clearly, there is still a need for better processes for the preparation of DTEA hydrochloride with the aim of: the reactants in the reaction process are effectively contacted, so that high reactant conversion rate and yield are obtained; the final homogeneous liquid product is formed after the process, and solidification/solid formation does not occur at lower temperatures (e.g., 32 ° F); controlling microbial growth by limiting the addition of more organic components; by using a solvent that serves both as a reaction co-solvent and as an LTS, the further step of adding LTS is eliminated, making the process more economical; and by using a larger portion of the water-based system for the reaction, it is easy to handle and has a low environmental impact.

Both processes on a commercial scale (EtOx and MEAH processes) result in the formation of a solid product or a phase separated mixture as a reaction concentrate at above room temperature (i.e., about 70 ℃) unless the reaction concentrate is sufficiently diluted with water or other diluent.

The EtOx process (Relenyi et al, WO 90/09983) involves the reaction of decenethiol with ethyl-2-oxazoline at about 140 ℃ in the absence of a solvent to form an intermediate that is immediately hydrolyzed in situ by additional heating and concentrated HCl to form DTEA hydrochloride. This material was pumped directly into another larger reaction vessel (to avoid solidification of the product in the reactor upon cooling and of sufficient size to dilute the product). The second vessel contains water and PG to form a reaction concentration medium similar to that obtained from the Mariam MEAH process.

The MEAH process involves the reaction of cysteamine hydrochloride with decene in propylene glycol, followed by dilution with water or a water-PG mixture, followed by further dilution with water (Mariam, us patent 5087757A, european patent application (1989), EP 320783 A2 19890621).

The reaction concentrate from EtOx was diluted prior to barreling to a typical content of about 18wt% dtea hydrochloride, 1698 wt% pg and 66wt% water. The MEAH process reaction concentrate can be readily prepared at 45-50 wt.% DTEA hydrochloride, or as a 15 wt.% DTEA hydrochloride solution in PG and water (about 15 wt.% DTEA hydrochloride, about 16 wt.% PG, and about 67% water) as described in Mariam (example 1). Brady indicated that a typical Mariam reaction concentrate consisted of 45 wt.% DTEA, 45 wt.% PG, 7 wt.% water, and 3 wt.% impurities.

The undiluted reaction concentrate from the marrimam reaction process must be barreled with the reaction mixture still hot, since the mixture solidifies at a temperature of about 60 ° F, forming a solid in solution even around typical room temperature. Commercial formulations typically contain about 5 to about 15wt% of DTEA hydrochloride, which is prepared by diluting the reaction concentrate with the appropriate amount of water. According to the solubility data (see fig. 1 and 2), a PG/water mixture of about 15wt% DTEA hydrochloride provides a solid-free solution of DTEA hydrochloride at room temperature, which can be used as the basis for wt% DTEA hydrochloride, PG and water in the reaction mixture (Mariam, example 1). The solubility of DTEA hydrochloride in the MEAH reaction concentration medium (Mariam, example 1) and EtOx process reaction medium (Relenyi, example 1), when each diluted with water, is about 15wt% at about 68 ° F, about 10wt% at about 63 ° F, and about 5wt% at about 55 ° F.

The barreled Mariam reaction concentrate is rigid at typical room temperature and must be heated to form a liquid in order to be removed from the barrel for further dilution or other formulation use.

Disclosure of Invention

The present invention describes an improvement to the known process for the production of 2- (n-decylthio) ethylamine hydrochloride (DTEA hydrochloride) wherein the reaction efficiency is increased and an additive that is both a Low Temperature Stabilizer (LTS) and a reaction co-solvent is added to provide a commercial formulation with improved low temperature stability and minimal post-reaction processing. The use of the claimed additives in the reaction and in the final formulation eliminates the need for separation of the reaction solvent, thereby reducing production costs.

More specifically, the present invention relates to a process for preparing 2- (n-decylthio) ethylamine hydrochloride (DTEA hydrochloride) comprising reacting decene and cysteamine hydrochloride with (a) a catalyst, (b) water, and (c) an additive of formula (a):

wherein:

ph is phenyl;

n is 0 or 1;

k is 2 to 4; and

m is 1 to 3;

it provides 2- (n-decylthio) ethylamine hydrochloride in about >90% yield as a concentrated mixture, wherein this concentrated reaction mixture is further diluted with water to provide a Low Temperature Stable (LTS) liquid product.

Other additives may be added to the concentrated reaction mixture either directly or as part of dilution with water, or after dilution with water. The additive is present in the final solution after dilution with water in an amount of about 1 to about 30 weight percent or about 2 to about 20 weight percent. The amount of additive used in the reaction is from about 10 to about 49 weight percent.

The low temperature stability of the resulting product is at a temperature of from about 32 ° F to about 60 ° F. By stable liquid product is meant that the product does not form a solid or any phase separation at low temperatures.

The amount of product present in the final solution is from about 2 to about 25 weight percent; or about 5 to 15 wt%.

The reaction is carried out at a temperature of about 70 ℃ to about 79 ℃ under an inert atmosphere.

The yield of the DTEA hydrochloride salt product of the present reaction is greater than 90%, typically greater than 95%, even when run on a commercial scale, and can be further optimized.

The selection of the additives and catalysts used in this process is not trivial and will be discussed further below.

Brief Description of Drawings

Figure 1 graphically represents the water solubility of DTEA hydrochloride in an untreated Mariam reaction mixture (i.e., about 47-51% DTEA hydrochloride, 18-21% PG, 21-27% water). LTS was not used and thus the data was comparable.

Figure 2 graphically represents the solubility of pure DTEA hydrochloride salt when the only solvent is water. This indicates the solubility of pure solid DTEA hydrochloride in water without LTS. The data is comparable.

Detailed Description

It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in this specification, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. The following terms in the glossary used in the present application will be defined as described below, and with respect to these terms, the singular includes the plural.

Various headings are given for the benefit of the reader, but are not intended to be the only locations where all aspects of the subject matter are referenced, and should not be construed as limiting the location of such discussions.

In addition, certain U.S. patents and PCT published applications have been incorporated by reference. However, the text of such patents is incorporated by reference only if there is no conflict between such text and other statements described herein. If such a conflict exists, none of such conflicting text in such incorporated by reference U.S. patents or PCT applications is expressly incorporated into this patent.

Glossary

The following terms used in the present application will be defined as described below, and with respect to these terms, the singular includes the plural.

Additive means a compound that is both a cosolvent (definition see below) and an LTS (definition see below)

AI represents an active ingredient

The azo catalyst preferably represents one of the following:

2,2' -azobis [ N- (2-carboxyethyl) -2-methylpropionamidine ];

2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride (VA 044);

2,2' -azobis [ 2-methyl-N- (2-hydroxyethyl) propionamide ];

4,4' -azobis (4-cyanovaleric acid); or alternatively

2,2' -azobis (2-methyl propionamidine) dihydrochloride (V-50)

BA represents benzyl alcohol, as shown in the following structure:

BTS refers to the GLTS subset defined by Brady, and is only applicable to the temperature stability of a particular formulation of DTEA hydrochloride

CA is cysteamine, 2-aminoethanethiol or 2-mercaptoethylamine

Co-solvent refers to the solvent used with water in the reaction of the present invention

Decene means 1-decene, C ₁₀ H ₂₀

DiEPh refers to diethylene glycol phenyl ether or 2- (2-phenoxyethoxy) ethanol, as shown in the following structure

DTEA is n-decylthioethylamine or 1-decylthioethylamine or 2- (1-decylthio) ethylamine

g represents g

GLTS refers to a well-known, widely used low temperature stabilizer, without defining the stability or temperature range of use, but rather for specific applications

h represents hour

HCl represents the hydrochloride salt

L represents L

LTS refers to compounds that are low temperature stabilizers, where a liquid solution remains homogeneous and does not become a solid, or contains no solids (precipitates), or does not phase separate at low temperatures (low temperature refers to about 32 ° F to about 60 ° F), and low temperature stability is determined by instrumental measurements or visual inspection to be free of solid particles (crystalline or other solid forms) or without any solidification of the liquid.

min represents minutes

mL means mL

PA represents 2-phenylethanol, as shown in the following structure

PE represents 2-phenoxyethanol and is shown in the following structure

PG represents propylene glycol and is represented by the following structure

PP represents 1-phenoxy-2-propanol and is represented by the following structure

RT means room or ambient temperature, from about 20 ℃ to about 25 ℃ or about 72 ℃ F

sec is seconds

Solid formation includes, but is not limited to, formation of a solid phase in the original liquid phase, including, but not limited to, crystallization; if the amount of solids is substantial, the entire volume may appear to be solid

Water refers to water purified by Reverse Osmosis (RO) as used in this example, but this is not critical

wt% means weight percent

Discussion of the preferred embodiments

In general, the above prior art establishes the use of GLTS in formulations, but provides no guidance for the selection of LTS, let alone obtaining a suitable co-solvent for the manufacturing process of DTEA hydrochloride.

The idea arising in these previous teachings is that the cryostabilizers are considered to be interchangeable general classes, so one can simply select any one of the myriad known GLTS agents. These GLTS agents are typically the last ingredient of the formulation to be described and often include the word "as needed". Thus, the selection of GLTS after The reaction does not provide guidance for The selection of a suitable reaction solvent, especially a free radical reaction, where The selection of solvent is critical to The success of The reaction (see, for example, litwilienko, G; beckwith, a.L.J.; ingold, K.U. "solvent importance often ignored in free radical synthesis. (The free overview of solvent in free radical synthesis)", chem.Soc.Rev.2011, 40 (5), 2157-2163. DOI.

There was no overlap between BTS taught by Brady and co-solvents taught by Mariam. In fact, the present inventors have now found that most BTSs are not generally good reaction co-solvents, and that good co-solvents are not generally good LTS. It is also noted that the Brady BTS data was generated using a DTEA hydrochloride formulation containing predominantly PG (45 wt%) and only 7wt% water. These data are not applicable to the identification of LTS and, even as a post-reaction additive, to the PG-free DTEA hydrochloride product solution.

The method of the invention

There is a need for an improved process that avoids the increase in processing time and cost, increases reactant conversion, and increases the yield of DTEA hydrochloride. It is also advantageous to dilute the DTEA hydrochloride reaction mixture with only water to provide a commercial formulation. Replacing the currently used DTEA hydrochloride reaction co-solvent with LTS as a co-solvent avoids the solidification/solid formation problems of such formulations. The use of traditional GLTS co-solvents (e.g. PG) followed by addition of LTS after the formulation production process requires additional equipment and complicates the formulation. The presence of GLTS co-solvent in commercial formulations (as done in prior art processes) dilutes AI, adds unnecessary production costs, and is essentially used only as a microbial food in a water treatment environment. Another factor when considering the use of organic materials as co-solvents relates to flammability. Whenever possible, higher flash point solvents are preferred over low flash point solvents. For example, considering that two BTSs mentioned by Brady, PE and 1-butanol, if both were actually used as co-solvents in the DTEA hydrochloride process, on this basis, PE (flash point 250 ° F) would be a better solvent than 1-butane (flash point 96 ° F).

The preferred forms of DTEA hydrochloride sold are liquids of various concentrations, for example, from about 5 to about 15 weight percent DTEA hydrochloride, with DTEA hydrochloride being most efficiently produced at higher concentrations in the reaction. Therefore, the reaction mixture must be diluted to obtain a final formulation that is marketable. Water is the preferred diluent solvent due to its low toxicity, low cost and environmental friendliness. Furthermore, water is not a nutrient for microbial growth during product application, and thus reducing the organic solvent content by increasing the water content provides benefits in application. Unfortunately, even at these low concentrations of DTEA hydrochloride, the aqueous mixture prepared by diluting the reaction product produced by the Mariam process (above) begins to cure at temperatures (32 ° F to 60 ° F) commonly used in storage and handling. Concentrations as low as 1-5wt% show problematic solid formation. It should also be noted that dilution of the crude product with additional propylene glycol, both the preferred reaction co-solvent taught by Mariam and a low temperature stabilizer commonly used in many applications, is not effective in the present process. That is, PG is not a valid LTS in this application. It would be very valuable if different co-solvents could be used that both provided high reaction yields of DTEA hydrochloride salt and also served as effective Low Temperature Stabilizers (LTS) in the diluted end-use product.

The reactants of the process are decene (soluble in many organic solvents, relatively insoluble in water) and CA-HCl (soluble in water systems). The process requires aqueous and organic co-solvents that serve multiple functions, including improving the homogeneity of the reaction process and providing LTS for the product formulation, as well as catalysts. When these two reactants are mixed with a solvent and a catalyst, a reaction occurs. Additives are required as co-solvents to ensure efficient contact and reaction of the reactants in the initial biphasic mixture in high reaction yields, which also serves as LTS for handling and storage of the desired end product. It has proven difficult to find a solution of this kindSpecific reaction Should be takenInNot only canAs co-solventsCan also be used forAs an additive to LTS. The formulation of the DTEA hydrochloride (product) from the reaction must be kept as a homogeneous liquid to provide accurate and simple product transport without solidification, phase separation, e.g. crystallization to form a solid (which is a problem in prior systems). Aqueous solutions with minimal organic content are preferred in the process and its final formulation because they are inexpensive, relatively harmless, and provide minimal organic nutrients for microbial growth, especially in end-use applications.

Water and LTS as co-solvents

The previous teachings indicate that aqueous Propylene Glycol (PG) is the reaction solvent of choice. Unfortunately, however, the product obtained from PG-based processes forms a solid at low temperatures (as defined above) when diluted with water, and LTS addition is required to obtain a homogeneous liquid at 32 ° F to 60 ° F.

Brady teaches the use of BTSs such as 2-Phenoxyethanol (PE) and 1-phenoxy-2-propanol (PP) with the DTEA hydrochloride product to provide a stable, homogeneous liquid at low temperatures. These BTSs are not used for the reaction, but are added after the product formation. None of the successful BTS reagents found by Brady were used or taught as co-solvents for the reaction, as described above, and their application range is limited; its use is only applicable to low water, high PG solvent mixtures in DTEA hydrochloride formulations. When LTS is also used as a co-solvent in the reaction, it is more cost-effective and efficient, as it eliminates the need and cost of any other co-solvent, such as Propylene Glycol (PG), that is strictly used in the reaction step. Thus, in a streamlined process, the formulated product can maintain its low temperature stability without the conventional handling steps of separating the co-solvent from the reaction mixture to isolate the AI and adding LTS to the AI in a separate formulation step.

The present process uses additives that are both co-solvents and LTS. This has the following advantages. The prior art neither recognizes nor attempts to identify co-solvents that are effective for the present reaction and are also LTS.

However, it is not a simple task to select an LTS that is also a good reaction co-solvent. LTS, which is generally used and widely preferred GLTS (such as propylene glycol (PP), glycerol or ethylene glycol) is inferior to DTEA hydrochloride. These prior art GLTS do not work well or at all in the present method. Aromatic ring functionality is also not a sufficient criterion for choosing LTS as a co-solvent, e.g., for the use of H in the present invention ₂ O ₂ Or the azo catalyst, of the present DTEA hydrochloride, neither Benzyl Alcohol (BA) nor 1-phenoxy-2-propanol (PP) are effective co-solvents, although both are referred to as excellent GLTS.

The additive of the invention, which is a co-solvent used in the reaction of the invention and which serves as LTS, may optionally be further added to the aqueous DTEA hydrochloride salt product solution to provide a liquid that is stable at temperatures as low as at least 32 ° F.

Formulations that form solids at low temperatures, such as those often encountered during storage and use of the product, are impractical and problematic. When solids form in the formulation, it is often difficult to restore homogeneity. Storage in specially heated storage areas to prevent temperature drop, or use of heat and agitation to melt and remix the mixture, is time consuming, expensive, and inconvenient. The heterogeneous mixture is difficult to pump, can clog nozzles and filters, cannot be metered well, and cannot be used to provide consistent or accurate doses.

Suitable co-solvents of the present invention are phenyl-containing alcohols, such as 2-Phenoxyethanol (PE) and 2-Phenylethanol (PA), preferably those having a significant water solubility of about 1 to about 10% by weight. The amount of additive (LTS/co-solvent) used in the reaction is from about 10 to about 49wt%, preferably from about 15 to about 35 wt%. The effective additive is represented by the following formula a:

wherein:

ph is phenyl;

n is 0 or 1;

k is 2 to 4; and

m is 1 to 3;

representative examples of such additives of formula a are PA, PE and DiEPh. Some examples of GLTS found to be ineffective as co-solvents are BA, PP and PG. It is therefore not clear and obvious for a person skilled in the art what will work as an additive in a process based on the reactions known at present.

In carrying out the current reaction, the mixture initially has two liquid phases; namely, an organic phase containing decene and an aqueous phase containing cysteamine hydrochloride (CA HCl). The latter aqueous phase also contains the catalyst. While not wishing to be bound by theory, it is believed that in order for the reaction to occur efficiently, the decene must have sufficient solubility in or contact with the aqueous phase. The benzyl alcohol co-solvents of the present invention have a proper balance of polar and non-polar character, which aids in the mixing and solubilization required in the reaction. These co-solvents also have the appropriate characteristics as LTS reagents to dissolve the final product at low temperatures of about 32 ° F to about 60 ° F to avoid solidification, solid formation and/or phase separation. These inventive LTS's are present in the final product solution in an amount of about 1 to about 30 weight percent, preferably about 2 to about 20 weight percent. Many of the previously used solvents do not have this property and do not provide these desirable results.

Catalyst/initiator

The process requires the use of a free radical initiator. When co-solvents are used with various catalysts/initiators, there are problems with solubility and which will work in the system. For example, mariam teaches hydrogen peroxide and azo initiators (including water insoluble azo initiators) (discussed above). However, the preferred azo initiator taught by Mariam is a water-insoluble azodinitrile. Mariam also does not provide data on azo initiators, and even water-soluble azo initiators were found to be ineffective with PG as a solvent in this test. However, surprisingly, azo catalysts using only PE or PA solvents produce the desired LTS product in the present reaction.

Preferred catalysts of the invention are water-soluble azo catalysts, for example:

2,2' -azobis (2-methylpropionamidine) dihydrochloride (V-50);

2,2' -azobis [ N- (2-carboxyethyl) -2-methylpropionamidine ];

2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride (VA-044);

2,2' -azobis [ 2-methyl-N- (2-hydroxyethyl) propionamide ]; and

4,4' -azobis (4-cyanovaleric acid).

The selection of these different reaction parameters does not readily achieve the desired results. While the results of Brady indicate that 2-Phenoxyethanol (PE) and PP are good BTSs for the diluted reaction product (added after the reaction is run), and Mariam teaches that the good reaction solvents are specific glycols and glycol ethers, mariam does not teach any of the Brady claimed BTSs as reaction solvents, nor any of the phenyl-substituted alcohols of formula (a). The current results indicate that good BTS and GLTS are not necessarily good reaction solvents (e.g., BA and PP) and vice versa, good reaction solvents are not good LTS [ e.g., PG (data and Brady), dowanol DPM (dipropylene glycol methyl ether, brady)]. Thus, it is not clear to the skilled person how to identify a successful solvent, i.e. additive, for both purposes. In fact, it is very pleasing to peopleSurprisingly, two structurally similar compounds, 2-Phenoxyethanol (PE) and PP, taught by Brady as good BTSs, gave very different results as reaction solvents, good and bad, respectively. Another solvent now identified as a good BTS is BA; however, it proved to be a poor reaction solvent. Another good cosolvent, diethylene glycol phenyl ether (Dowanol DiEPh), was found to be a good LTS for DTEA hydrochloride. The data and observations in this application show that the successful reaction results depend not only on the solvent but also on the catalyst. Comparison of the data in tables 1 and 2 shows H ₂ O ₂ The results are good, but the results are poor at V-50.

If the skilled person were to randomly screen the list of solvents taught by Brady and other solvents (e.g. alcohols) of similar structure with H ₂ O ₂ And V-50 (and possibly other commercially available free radical initiators), and at different solvent concentrations and different amounts of water, the number of combinations to be tested would be very large, requiring undo experimentation and impractical testing times, making the ultimate selection of a successful reaction solvent for the present process impractical. Finding them by testing alone is daunting, as the list to test can be very large under a number of conditions, and the reactions are actually run to determine what is valid for the expected result. Thus, it is not feasible to simply replace several items to see what; rather, it requires a number of variables and significant experimentation to find what is now claimed.

Clearly, previous attempts to make DTEA hydrochloride without LTS have difficulty in achieving high reactant conversions and yields, without phase separation, solidification, or solid formation at lower temperatures (e.g., 32 ° F); difficulty in controlling the growth of microorganisms by limiting the organic constituents; difficulty in eliminating the need for solvent or product separation steps; and are difficult to handle and have low environmental impact by using a larger portion of the water-based system. The process of the present invention provides these advantages.

The present process provides a final product formed by the reaction of the present invention, which comprises as a solution: a) About 2 to 25% by weight of DTEA hydrochloride, preferably about 5 to about 15% by weight, b) additional water and additives, if necessary added after the reaction, in an amount of about 1 to about 30% by weight of additives, preferably about 2 to about 20% by weight. The final product provides low temperature stability of at least 32 ° F to about 60 ° F. The invention will be further elucidated by considering the following examples, which are intended purely as illustrations of the invention.

The alphabetical embodiment is a comparative example. The numbered examples are directed to compounds of the invention.

Material

Decene was purchased from Shell.

DiEPh is available from DowDupont.

PE is from Nexeo.

Benzyl alcohol and PA were purchased from Sigma-Aldrich.

PP was obtained from GNS Technologies LLC.

CA HCl was purchased from Hangzhou advanced technologies, inc.

The water is prepared by Reverse Osmosis (RO).

V-50 was purchased from Wako.

VA-044 was purchased from Sigma-Aldrich.

H ₂ O ₂ Purchased from GFS Chemicals, inc, as a 50% aqueous solution, then diluted with water to a 1.5-1.8% solution.

Pure solid DTEA hydrochloride was prepared by the method described in US 5087757 and isolated by dilution and acetonitrile crystallization.

General reaction conditions

The general reaction conditions of the invention are:

a temperature of from about 25 ℃ to about 120 ℃ (preferably from about 74 ℃ to 77 ℃);

the atmosphere is air, nitrogen or argon;

the catalyst concentration is from about 0.01 to about 5wt%, preferably from about 0.1 to about 1 wt%;

decene concentration from about 1 to about 40 wt%, preferably from about 15 to about 30 wt%;

cysteamine hydrochloride concentration is about 1 to about 40 wt%, preferably about 15 to about 30 wt%;

water concentration from about 10 to about 49wt%, preferably from about 15 to about 35 wt%;

the additive concentration is from about 10 to about 49 weight percent, preferably from about 15 to about 35 weight percent; and

optionally: adding 36wt% to about 0.01 to about 1wt% HCl; about 1 to about 5 wt.%, preferably about 0.5 to about 2 wt.% of DTEA hydrochloride is added.

Preparation and comparison of DTEA hydrochloride

₂ ₂ Example 1: general procedure for HO as catalyst

Using 72g decene, 62g CA HCl, 50-75g cosolvent, 44g water, 2.75g DTEA hydrochloride, 26-30mL H ₂ O ₂ 0.1mL concentrated HCl, the following general procedure was run using the various co-solvents shown.

To a three-necked flask equipped with a mechanical stirrer, thermocouple, addition funnel, and nitrogen inlet was added cysteamine hydrochloride, co-solvent, water, and DTEA hydrochloride. The system was purged with nitrogen and the reaction was carried out under a nitrogen atmosphere. The mixture was stirred and heated to 65 ℃ using a water bath. To this mixture was added 0.1mL concentrated HCl followed by 10mL decene. The addition of hydrogen peroxide solution and remaining decene is then started and the reaction temperature is maintained below 80 ℃ (preferably about 74 ℃ to 77 ℃). The hydrogen peroxide solution was added over 40 minutes. Decene was added over 20 minutes. After the hydrogen peroxide addition is complete, the reaction mixture is stirred for an additional 1 hour while maintaining the reaction temperature below about 80 ℃ (preferably about 74 ℃ to about 77 ℃). The mixture was cooled and analyzed. The results are shown in table 1 below.

Table 1: DTEA hydrochloride process using hydrogen peroxide and various co-solvents

There are two layers orThree layers demonstrate low conversion and yield. These results indicate that PG, PE and PA are in H ₂ O ₂ Effective co-solvents in the case of catalysts. BA and PP have poor effects and low product yield.

Example 2: general procedure for V-50 as catalyst

The following general procedure was run using 72g decene, 62g CA HCl, 75g co-solvent, 75g water, 2.75g DTEA hydrochloride, 0.39-0.78g V-50[2,2' -azobis (2-methylpropionamidine) dihydrochloride ] in 10mL RO water, 0.1mL concentrated HCl.

To a three-necked flask equipped with a mechanical stirrer, thermocouple, addition funnel, and nitrogen inlet was added cysteamine hydrochloride, co-solvent, water, and DTEA hydrochloride. The system was purged with nitrogen and the reaction was carried out under a nitrogen atmosphere. The mixture was stirred and heated to 65 ℃ using a water bath. To this mixture was added 0.1mL concentrated HCl followed by 10-15mL decene. About 5mL of the V-50 solution was then added and stirring was continued. The remaining decene was added dropwise to the reaction mixture over 30-35 minutes. The reaction temperature is kept below 80 ℃ (preferably 74 ℃ to 77 ℃). After about 50mL of decene was added, another portion of V-50 (5 mL) was added and stirring was continued. After the decene addition is complete, stirring is continued for an additional 1.5-2 hours while maintaining the reaction temperature below 80 ℃ (preferably about 74 ℃ to 77 ℃). The mixture was cooled and analyzed. The results are shown in table 2 below.

Table 2: DTEA hydrochloride process using V-50 and various co-solvents

NA = unanalyzed

These results indicate that PE and PA are effective as co-solvents. PG, PP, and BA were not effective.

Example 3: comparison of PE and PG

About 5wt% to about 10wt% PE was added to a 15wt% DTEA solution (prepared from commercial DTEA hydrochloride concentrate by dilution with water), resulting in a homogeneous solution after storage for extended periods of time, both at room temperature and at 32 ° F, after several days. The weight percent of DTEA hydrochloride in the solution after addition to PE ranges from about 6.5 wt% to about 7 wt%.

Similarly, 13 to about 16wt% PE was added to a 15wt% DTEA solution (prepared from commercial DTEA hydrochloride concentrate by dilution with water) and stored for a long period of time at room temperature and 32 ° F-after several days to yield a homogeneous solution. Below about 13 wt% PE, the solution is a homogeneous solution at room temperature, but is a solid at 32 ° F. The weight percent of DTEA hydrochloride in the solution after addition to PE ranges from about 12.5 wt% to about 13 wt%.

It should be noted that these formulations, like the reaction to make DTEA hydrochloride, require a delicate balance between water and organic additives to maintain homogeneity. Either too much or too little addition can affect the low temperature stability of the cure and can also affect the homogeneity of the mixture at higher temperatures due to phase separation. These studies only included the results that the solution remained homogeneous throughout the temperature range of the study. Only solutions that are the lower limit of additive concentrations for which LTS is effective for a given solution were investigated. The goal is to add about the minimum amount of effective organic LTS, as this is both economically and microbiologically prudent.

In directly comparing the effectiveness of PE versus PG, a 16.7wt% DTEA solution (prepared as described above for 7.5 and 15wt% solutions) was diluted with PE or PG to provide a solution containing 13.9wt% DTEA hydrochloride and 16.6wt% PG or PE.

Both solutions were homogeneous at room temperature. The DTEA hydrochloride formulation containing PE remained homogeneous at 32 ° F, while the DTEA hydrochloride/PG formulation solidified rapidly and remained solid.

For further comparison, referring to figure 1, the solubility of DTEA hydrochloride in water as a crude processed DTEA hydrochloride Mariam reaction mixture and pure DTEA hydrochloride solid was determined at different temperatures. A Mariam reaction mixture was prepared using a hydrogen peroxide catalyst and a PG co-solvent. The mixture contains about 50 wt.% DTEA hydrochloride, 20 wt.% PG, and 30 wt.% water). Pure DTEA hydrochloride was isolated from Mariam reaction mixture by adding acetonitrile, cooling the mixture on ice and collecting white DTEA hydrochloride solid (dry before use).

When the Mariam DTEA hydrochloride reaction mixture was diluted to 20wt% DTEA hydrochloride by water, a solid formed at 71 ℃ F. The Mariam reaction mixture was further diluted with water to 5wt% DTEA hydrochloride to give a solution that formed a solid at even lower temperature (55 ° F), see fig. 1. In contrast, the solubility of pure DTEA hydrochloride in water was 11 wt% at 67 ° F and less than 1wt% at 56 ° F (see fig. 2). PG is a better solvent than water for DTEA hydrochloride, but PG does not provide Low Temperature Stability (LTS) to the mixture containing it.

Example 4:2,2' -azobis [2- (2-imidazolin-2-yl) propane]Using dihydrochloride (VA 044) as catalyst Procedure

The general procedure outlined in example 2 was carried out using 72g decene, 62g CA HCl, 75g co-solvent, 75g water, 2.75g DTEA hydrochloride, 0.6wt% VA-044 in 10ml reverse osmosis water. No solid DTEA hydrochloride was added to the reaction. Analysis showed that the yield of DTEA hydrochloride was 77.4% and the conversion in 2 hours was 81%.

Example 5: dilution process

Part A: propylene glycol/Hydrogen peroxide Process-dilution with Water and 2-Phenoxyethanol (PE)

The DTEA hydrochloride product mixture (200g, 50 wt% DTEA hydrochloride) was mixed with 380g of water and 86.6g of 2-Phenoxyethanol (PE) at room temperature to give 666.6g of 15% DTEA hydrochloride as a clear solution containing 13% 2-Phenoxyethanol (PE). Further dilution with water 1.

And part B: 2-Phenoxyethylalcohol/V-50 Process-dilution with Water and 2-Phenoxyethanol (PE)

The DTEA hydrochloride product mixture (270g, 47.4 wt% DTEA hydrochloride) was mixed with 544g of water and 39g of 2-Phenoxyethanol (PE) at room temperature to give 853g of 15-% DTEA hydrochloride as a clear solution containing 13% 2-Phenoxyethanol (PE) (270 g of the product mixture already containing 72g of PE). Further dilution with water 1.

Example 6: crystallization behavior

Part A: mariam reaction (propylene glycol/Hydrogen peroxide method diluted with Water and 2-Phenoxyethanol (PE))

The 15-percent DTEA hydrochloride solution containing 13-percent 2-phenoxyethanol and the 7.5-percent DTEA hydrochloride solution containing 6.5-percent 2-phenoxyethanol prepared from the crude mixture obtained by the propylene glycol/hydrogen peroxide process (example 5A above) remained homogeneous liquids when the temperature was reduced to 32F.

Furthermore, the 16.4% DEA HCl solution, containing 10.34% PE, did not cause any precipitation or crystallization of solids after storage in the refrigerator for two days.

In contrast, this result may be contrasted with fig. 1, where phenoxyethanol is not present and solid formation occurs at 32 ° F.

And part B: reaction product from 2-phenylethanol/V-50 process diluted with water and 2-Phenoxyethanol (PE)

1) A15-percent DTEA hydrochloride solution containing 13-percent 2-phenoxyethanol prepared from the crude product mixture obtained from the 2-phenoxyethanol/V-50 process (example 5B above) was a slightly hazy solution at 32 ℃ F. However, no filterable solids are formed at this temperature.

In contrast, this result may be in contrast to fig. 1, where phenoxyethanol is not present and solids formation occurs at 32 ° F.

2) 7.5% DTEA hydrochloride solution prepared from the crude product mixture obtained from the 2-phenoxyethanol/V-50 process (example 5B above) containing 6.5% 2-phenoxyethanol was a homogeneous liquid at 32 ℃ F.

And part C: purified DTEA hydrochloride diluted with water and 2-Phenoxyethanol (PE)

The first 15% containing 2-phenoxyethanol prepared from DTEA hydrochloride (isolated by crystallization of the crude product mixture using acetonitrile) and the second 7.5% containing 6.5% 2-phenoxyethanol were homogeneous liquids at 32 ℃ F.

In contrast, DTEA hydrochloride is substantially insoluble in water at 32 ° F, and 15wt% aqueous DTEA hydrochloride solution forms a solid above room temperature. (see FIG. 2).

Application method of DTEA hydrochloride

The product DTEA hydrochloride formed by the process of the present invention is used in industrial water treatment systems for biofouling and corrosion control.

Although the present invention has been described with reference to preferred embodiments thereof, it will be understood by those of ordinary skill in the art upon reading and understanding the present disclosure that changes and modifications may be made without departing from the scope and spirit of the invention as described above or claimed below. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the general manner of carrying out the invention.

Claims

1. A process for preparing 2- (n-decylthio) ethylamine hydrochloride comprising reacting decene and cysteamine hydrochloride with (a) a catalyst, (b) water, and (c) an additive of formula (a):

wherein:

ph is phenyl;

n is 0 or 1;

k is 2 to 4; and

m is 1 to 3;

it provides 2- (n-decylthio) ethylamine hydrochloride in about >90% yield as a concentrated reaction mixture, wherein such concentrated reaction mixture is further diluted with water to provide a Low Temperature Stable (LTS) liquid product.

2. The process of claim 1, wherein additional additives are added to the concentrated reaction mixture directly or as part of dilution with water, or after dilution with water.

3. The method of claim 1 or 2, wherein the additive is 2-Phenoxyethanol (PE), 2-Phenylethanol (PA) or diethylene glycol phenyl ether (DiEPh).

4. The process of claim 1 or 2 wherein the catalyst is H ₂ O ₂ Or an azo catalyst.

5. The process of claim 4, wherein the azo catalyst is 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride; 2,2' -azobis (2-methylpropionamidine) dihydrochloride; 2,2' -azobis [ N- (2-carboxyethyl) -2-methylpropionamidine ];2,2' -azobis [ 2-methyl-N- (2-hydroxyethyl) propionamide ]; or 4,4' -azobis (4-cyanovaleric acid).

6. The process of claim 5, wherein the azo catalyst is 2,2' -azobis (2-methylpropionamidine) dihydrochloride.

7. The method of claim 1, wherein a stable liquid product means no second phase separation or no solids formation.

8. The process of claim 1, wherein the additive is 2-Phenoxyethanol (PE), 2-Phenylethanol (PA) or diethylene glycol phenyl ether (DiEPh) and the catalyst is 2,2' -azobis (2-methylpropionamidine) dihydrochloride.

9. The process of claim 1 wherein the additive is 2-Phenoxyethanol (PE), 2-Phenylethanol (PA) or diethylene glycol phenyl ether (DiEPh) and the catalyst is H ₂ O ₂ 。

10. The method of claim 1, wherein 2- (n-decylthio) ethylamine hydrochloride is present in an amount from about 2 to about 25wt% after dilution with water.

11. The method of claim 1, wherein 2- (n-decylthio) ethylamine hydrochloride is present in an amount from about 5 to about 15% by weight after dilution with water.

12. The method of claim 1, wherein the additive is present in an amount of about 1 to about 30wt% after dilution with water.

13. The method of claim 1, wherein the additive is present in an amount of about 2 to about 20wt% after dilution with water.

14. The process of claim 1 wherein the amount of additive used in the reaction is from about 10 to about 49wt%.

15. The method of claim 1, wherein the reaction is carried out at a temperature of about 70 ℃ to about 79 ℃ under an inert atmosphere.