Note: Descriptions are shown in the official language in which they were submitted.
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PROCESS FOR PREPARING DTEA HO
BACKGROUND OF THE INVENTION
Field of the Invention
This invention generally concerns an improved process for preparing DTEA HC1
from 1-
decene and cysteamine HC1 (CA HC1).
Background of the Invention
Industrial chemicals are most commonly manufactured using solvent-based
reaction
methodology, followed by isolation, purification, and packaging. Many such
chemical products
are then formulated into a commercial product by blending the active
ingredient (Al; see
Glossary below for a full listing of abbreviations and acronyms) with other
materials optimized
for, and specific to, its end use. When formulated as an aqueous solution,
often problems with
solidification and or Al precipitation can become an issue when formulations
are stored at (or in
some cases, even briefly subjected to) below room temperature environments.
Partial
precipitation and settling of solids result in variable Al concentration as
well as inaccurate and
inefficient transfers of the formulation from storage to end-use vessels.
Solids may cause major
difficulties with clogging filters and/or nozzles in applications requiring
the formulation be
pumped or sprayed. Thus, the ability to remain as a pumpable, homogeneous
material that is
free of solids is essential to avoid costly and inconvenient heating and
agitation operations during
formulation operations and use.
Description of Related Art
Several patents disclosed use of additives in microbiocidal formulations to
increase low
temperature stability (to hinder Al precipitation or formulation
solidification). A few of such
patents are provided below. None of this next listed art uses GLTS agents (as
defined in the
Glossary below) as a co-solvent for the reaction to make DTEA HC1.
US Pub Appin. 2008/0076803 (Beilfuss) describes addition of one or more
aromatic
alcohols to 1,2-benzoisothiazolin-3-one formulations to increase low
temperature stability.
Specifically, the preferred additives are chosen from (i) aryloxyalkanols
(glycol monoaryl
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ethers), (ii) arylalkanols and (iii) oligoalkanol aryl ethers or mixtures
thereof. This reference
proscribes in Claim 13 a sequence for preparation of a formulation specifying
the GLTS is the
last component to be added, and is not taught or used in any GLTS-co-solvent
process of this
reference.
W02001/041570 (Beilfuss) describes use of the same suite of additives as those
in US
2008/0076803 above but they are used to improve the stability and lessen
inhomogeneity of a
different mixture of AIs.
US Pub Appin 2013/0217579 (Wacker) describes a new low temperature solvent for
pesticide formulations and includes addition of GLTS propylene glycol (PG) and
glycerol to said
formulations.
US 5,371,105 (Damo) describes novel aqueous formulations of agrochemical
active
substances which are sparingly soluble in water. These formulations are either
water-in-oil or
oil-in-water emulsions. One additive to the formulation is GLTS, preferably
glycerol, but also
mentions EG, PG, and polyglycols.
US 5,369,118 (Reizlein) teaches the use of GLTS auxiliaries to improve the
stability of
triazole fungicide formulations to retard solids formation in aqueous spray
liquors to prevent
clogging spray nozzles and in-line filters. PG and glycerol are preferred.
US 5,206,225 (Horstmann) teaches use of GLTS auxiliaries to improve the
stability of
triazole fungicide formulations to retard solids formation in aqueous spray
liquors to prevent
clogging spray nozzles and in-line filters. PG and glycerol are preferred.
US 7,368,466 (Beilfuss) discloses a water-based formulation of the fungicide,
a salt of
carbedazim, containing certain GLTS exhibit long-lasting low temperature
stability. Beilfuss, et
al. cite benzyl alcohol (BA) as a preferred GLTS and 1-phenoxy-2-propanol (PP)
as a
particularly preferred GLTS; neither of these is a satisfactory LTS-co-solvent
in the DTEA HC1
process described herein.
US 5,087,757 (Mariam) taught the use of various solvents in the reaction of
decene and
CA HC1 (2-aminoethanethiol hydrochloride, also referred to as cysteamine HC1)
to produce
DTEA HC1 using catalysts/initiators including hydrogen peroxide and azo
initiators. These
included glycols and glycol ethers, and their mixtures with water. Examples
mentioned are:
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ethylene glycol; propylene glycol; propylene glycol methyl ether; dipropylene
glycol methyl
ether; diethylene glycol; triethylene glycol; tetraethylene glycol; and
dipropylene glycol, with
propylene glycol and tetraethylene glycol preferred. Some of the disadvantages
of using the
Mariam reaction to produce DTEA HC1 are: (1) achieving high conversion of
reactants is
difficult and requires multiple additions of catalyst and extended reaction
times to achieve high
conversion of reactants to DTEA HC1; and (2) dilution with the preferred
solvent (water)
produces a formulation with serious solidification/solids formation problems
at low temperatures
(defined as about 32 F to about 60 F).
US H1265 Statutory Invention Registration (Brady) taught a variety of alcohol
(hydroxyl
group-containing) additives that could be added to the DTEA HC1 reaction
product prepared by
the Mariam process (using PG or tetraethylene glycol (TEG) as a reaction
solvent). This Brady
technique dilutes the reaction product mixture with BTS (as defined in the
Glossary below) to
provide low temperature stability. BTS solvents mentioned are butyl alcohol,
cyclohexanol,
hexyl alcohol, isobutyl alcohol, ethylene glycol phenyl ether (a synonym for 2-
phenoxyethanol
(PE)) and propylene glycol phenyl ether (a synonym for 1-phenoxy-2-propanol
(PP)) and
mixtures thereof. Some of the disadvantages of using Brady's BTS with the
products of these
processes are: 1) addition of the BTS to the organic solvent-based reaction
mixture results in
higher overall product costs; and 2) adding additional organic chemicals to
the formulation is
problematic in the application of this product in industrial water treatment:
organic solvents in
the formulation are nutrients for microbial growth and make its control more
challenging and
costlier. The amount of organic solvent in the formulation should be minimized
to the extent
possible. A major limitation to extrapolation of Brady to other solutions is
that the screening for
low temperature stabilization was done, specifically, on a solution of DTEA
HC1 consisting of
(approximately) 45 wt% DTEA, 45 wt% PG, 7 wt% water, and 3 wt% impurities.
Although PG
is not LTS for this formulation, PG is a better solvent for DTEA HC1 than
water. Brady's
findings do not correlate well to other DTEA HC1 formulations that do not
contain PG.
US 5,025,038 (Relenyi) describes an ETOX process using PG as solvent to make
DTEA
HC1 to afford low temperature stability; however, this process has similar
solidification/solids
formation problems as Mariam at low temperatures.
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Clearly, there is still a need for a better process to make DTEA HC1 in order
to: obtain
effective contact of the reactants in the reaction process to obtain high
reactant conversion and
yield; have a final homogeneous liquid product formed after the process with
no
solidification/solids formation occurring at lower temperatures such as 32 F;
control microbial
growth by limiting adding more organic components; have a more economical
process by using a
solvent serving as both a reaction co-solvent and LTS that eliminates a
further step for the
addition of LTS; and have ease of handling with low environmental impact by
using a larger
portion of an aqueous based system for the reaction.
The two methods for industrial-scale production (the EtOx and MEAH processes)
result
in formation of a solid product or a phase- separated mixture at above room
temperature (i.e.,
about 70 F) as a reaction concentrate unless the reaction concentrate is
sufficiently diluted with
water or other diluents.
The EtOx process (Relenyi, et. al, WO 90/09983) involves a reaction of
decenethiol with
ethyl-2-oxazoline without solvent at about 140 C to form an intermediate that
is immediately,
in situ, hydrolyzed with additional heat and conc. HC1 to form DTEA HC1. This
material is
directly pumped into another, larger reaction vessel (to avoid solidification
of the product in the
reactor as it is cools and of sufficient size for product dilution). The
second vessel contains water
and PG to form a reaction concentrate medium similar to that obtained from the
Mariam MEAH
process.
The MEAH process involves a reaction of cysteamine HC1 with decene in
propylene
glycol which then diluted with water or a water-PG mixture which is then
further diluted with
water (Mariam, U.S.Pat. 5087757A, Eur. Pat. Appl. (1989), EP 320783 A2
19890621).
The reaction concentrate from the EtOx is diluted before drumming and has a
typical
content of about 18 wt% DTEA HC1, 16 wt % PG, and 66 wt % water after
dilution. The MEAH
process reaction concentrate can be made readily at 45-50 wt% DTEA HC1 or, as
described in
Mariam (Example 1), as a 15 wt% DTEA HC1 solution in PG and water (-15 wt%
DTEA HC1,
¨16 wt % PG, and ¨67 % water). Brady notes that a typical Mariam reaction
concentrate consists
of 45 wt% DTEA, 45 wt% PG, 7 wt% water, and 3 wt% impurities.
The undiluted reaction concentrate from the Marriam reaction process must
drummed
while the reaction mixture is still hot because the mixture solidifies at
around 60"F and can form
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solids in the solution even around typical room temperature. Commercial
formulations typically
contain from about 5 to about 15 wt% DTEA HC1 prepared by dilution of the
reaction
concentrate with the appropriate amount of water. From solubility data (see
Figures land 2), ¨15
wt% DTEA HC1 a PG/water mixture provides a solid-free solution of DTEA HC1 at
room
temperature, and this serves as a basis for the wt % DTEA HC1, PG and water in
reaction
mixture (Mariam, Example 1). The solubility of DTEA HO in the MEAH reaction
concentrate
medium (Mariam, Example 1) and of the EtOx process reaction medium (Relenyi,
Example 1)
when each is diluted with water is about 15 wt% at about 68 F, about 10 wt %
at about 63 F,
and about 5 wt% at 55 F.
The drummed Mariam reaction concentrate is rock solid at typical room
temperatures and
must be heated to form a liquid in order to get it out of the drum for further
dilution or other
formulation uses.
BRIEF SUMMARY OF THE INVENTION
The present invention describes an improvement over known processes for the
production of 2-(n-decylthio)ethylamine HC1 (DTEA HC1) in which the reaction
efficiency is
improved and incorporates an Additive that is both a low temperature
stabilizer (LTS) and a
reaction Co-solvent to provide a commercial formulation with improved low
temperature
stability with minimal post reaction processing. Use of the claimed Additive
in the reaction, as
well as the final formulation, eliminates the need of a separate reaction
solvent and thereby
reduces the production cost.
More specifically, the present invention concerns a process for preparing 2-(n-
decylthio)ethylamine HC1 (DTEA HC1) comprising reacting decene and cysteamine
HC1, with
(a) a catalyst, (b) water, and (c) an Additive of the Formula (A):
Phf(0),(CH2)kt OH
Formula (A)
wherein:
Ph is phenyl;
n is 0 or 1;
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k is 2-4; and
m is 1-3;
that provides the 2-(n-decylthio)ethylamine HC1 as a concentrated mixture in
about >90% yield,
wherein such concentrated reaction mixture is further diluted with water to
provide a low
temperature stable (LTS) liquid product.
Additional Additive can be added directly to the concentrated reaction mixture
or as part
of the dilution with water or after the dilution with water. The amount of
Additive present after
dilution with water in the final solution is from about 1 to about 30 wt% or
from about 2 to about
20 wt%. The amount of Additive used in the reaction is from about 10 to about
49 wt%.
The low temperature stability of the resulting product means at temperatures
from about
32 F to about 60 F. A stable liquid product means that the product has no
solids formation or
separation of any phases at the low temperatures.
The amount of product present in the final solution is from about 2 to about
25 wt%; or
from about 5 to 15 wt%.
The reaction is run under an inert atmosphere, at a temperature from about 70
C to about
79 C.
The yield of the DTEA HC1 product from the present reaction is >90%, often
>95%, even
when run on a commercial scale and can be further optimized.
The selection of the Additive and catalyst used in this process is not trivial
and discussed
further below.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 graphically represents the water solubility of DTEA HC1 in an
unprocessed
Mariam reaction mixture (i.e., approximately 47-51% DTEA HC1, 18-21% PG, 21-
27% water).
There is no LTS used so the data is comparative.
Figure 2 graphically represents the solubility of pure DTEA HC1 when the only
solvent
is water. This shows the solubility of pure solid DTEA HC1 in water with no
LTS used. The data
is comparative.
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DETAILED DESCRIPTION OF THE INVENTION
It is 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 indicates
otherwise. The following terms in the Glossary as used in this application are
to be defined as
stated below and for these terms, the singular includes the plural.
Various headings are present to aid the reader, but are not the exclusive
location of all
aspects of that referenced subject matter and are not to be construed as
limiting the location of
such discussion.
Also, certain US patents and PCT published applications have been incorporated
by
reference. However, the text of such patents is only incorporated by reference
to the extent that
no conflict exists between such text and other statements set forth herein. In
the event of such
conflict, then any such conflicting text in such incorporated by reference US
patent or PCT
application is specifically not so incorporated in this patent.
Glossary
The following terms as used in this application are to be defined as stated
below and for
these terms, the singular includes the plural.
Additive means a compound that is both a Co-solvent (defined below) and LTS
(defined
below)
AT means active ingredient
azo catalyst means, preferably, 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
2,2'-Azobis(2-methylpropionamidine) dihydrochloride (V-50)
BA means benzyl alcohol, as depicted by the following structure
OOH
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BTS means an GLTS subset as defined by Brady and applicable only to
temperature
stability of a specific formulation of DTEA HC1
CA means cysteamine or 2-aminoethanethiol or 2-mecaptoethylamine
Co-solvent means a solvent used with water in the reaction of this invention
Decene means 1-decene, C10H20
DiEPh means diethyleneglycol phenylether or 2-(2-phenoxyethoxy)ethanol, as
depicted
by the following structure
40 õ...---....õõØ.........õ...-..._
0 OH
DTEA means n-decylthioethylamine or 1- decylthioethylamine or 241-
decylthio)ethylamine
g means grams
GLTS means generally well known, widely used low temperature stabilizers
without
defining the stabilization or temperature range of use but for specific
applications
h means hour or hours
HC1 means a hydrochloride salt
L means liter
LTS means a compound that acts as a low temperature stabilizer, in which a
liquid
solution remains homogeneous and does not become solid, or contain solids
(precipitates), or undergo phase separation at low temperature (low
temperature
means from about 32 F to about 60 F) and low temperature stability is
determined by instrument measurement or visually by the absence of solid
particulates (crystalline or other solid forms) or by absence of any
solidification of
the liquid.
mm means minute or minutes
mL means milliliter
PA means 2-phenylethanol as depicted by the following structure
OH
PE means 2-phenoxyethanol, as depicted by the following structure
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401 OH
0
PG means propylene glycol, as depicted by the following structure
OH
HO
CH3
PP means 1-phenoxy-2-propanol, as depicted by the following structure
0 OH
5 CH3
RT means room temperature or ambient temperature, from about 20 C to about 25
C or
about 72 F
sec means second
Solids formation includes but is not limited to formation of a solid phase
within the
10
original liquid phase, which includes but is not limited to crystallization;
if the
amount of solid is substantial, the entire volume may appear solid
Water means water purified by reverse osmosis (RO) as used in the present
examples,
but this is not critical
wt% means percent by weight
Discussion
In aggregate, the above prior art establishes the utility of GLTS in
formulations but
provides no guidance for selection of LTS, let alone one that would be a
suitable Co-solvent for a
DTEA HC1 manufacturing process.
The philosophy that emerges in these prior teachings is that low temperature
stabilizers
are thought of as an interchangeable, generic class such that one may simply
choose any one of a
myriad of known GLTS agents. These GLTS agents are generally the last
component of the
formulation to be described and commonly include the phrase 'as needed'. As
such, post-
reaction GLTS selection provides no guidance for selection of a suitable
reaction solvent,
especially free radical reaction where solvent selection is especially
critical to reaction success
(see, for example, Litwinienko, G.; Beckwith, A. L. J.; Ingold, K. U. "The
frequently overlooked
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importance of solvent in free radical syntheses" Chem. Soc. Rev. 2011, 40 (5),
2157-2163. DOT:
10.1039/C 1CS 15007C).
There is no overlap in the BTS taught by Brady, and the co-solvents taught by
Mariam.
Indeed, it has now been found by this invention that most BTS are not
generally good reaction
Co-solvents and also that good co-solvents are not generally good as LTS. It
is also important to
note that the Brady BTS data were generated using a DTEA HC1 formulation
containing mainly
PG (45 wt%) and only 7 wt% water These data are not applicable for
identification of LTS, even
as a post reaction additive, for a solution of DTEA HC1 product that does not
contain PG.
Present Process
An improved process is needed to avoid the increased processing time and
costs, to
improve the conversion of reactants, and to improve the yield DTEA HC1. It
would also be
advantageous to use only water for dilution of the DTEA HC1 reaction mixture
to provide a
commercial formulation. Replacing currently used DTEA HC1 reaction co-solvents
with LTS as
a Co-solvent avoids the solidification/solids formation issue of such
formulations. Using
traditional GLTS co-solvents (such as PG), then adding LTS in the post
production formulation
process, requires additional equipment and complicates formulation. The
presence of GLTS co-
solvent in the commercial formulation (as done in the prior art processes)
dilutes the AT, adds
unnecessary cost to production, and essentially serves only as food for
microorganisms in a
water treatment environment. Another factor when considering an organic
material for use as a
Co-solvent concerns flammability. Solvents with higher flash points are
preferred over low flash
point solvents whenever possible. For example, considering two of Brady's
mentioned BTS,
namely PE and 1-butanol, if both actually worked as a Co-solvent in the DTEA
HC1 process, PE
(flash point 250 F) would be the preferred solvent over 1-butanol (flash point
96 F) on this
basis.
A preferred form of DTEA HC1 for sale is a liquid in various concentrations,
for example
about 5 to about 15 wt% DTEA HC1, whereas the DTEA HC1 is produced most
efficiently at a
higher concentration in the reaction. Thus, the reaction mixture must be
diluted to yield the final
formulation for sale. Water is the preferred dilution solvent due to its low
toxicity and low cost
and environmental preference. Also, water is not a nutrient for microbial
growth during product
application, so lowering organic solvent content by increasing the water
content provides benefit
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in applications. Unfortunately, even at these low concentrations of DTEA HC1,
aqueous
mixtures prepared by dilution of the reaction product produced by the Mariam
process (above)
begin to solidify at temperatures that are commonly used in storage and
handling (32 F to 60 F).
Concentrations as low as 1-5 wt% showed problematic solids formation. It
should also be noted
that dilution of the crude product with additional propylene glycol, both a
preferred reaction co-
solvent taught by Mariam and a commonly used low temperature stabilizer in
many applications,
is NOT effective for this present process. That is, PG is not an effective LTS
in this application.
It would be of great value to be able to use a different co-solvent that BOTH
afforded a high
reaction yield of DTEA HC1 and functioned as an effective low temperature
stabilizer (LTS) in
the diluted, end-use product.
The reactants for this present process are decene (which is soluble in several
organic
solvents and relatively insoluble in water), and CA HC1 (which is soluble in
aqueous systems).
The present process requires a water solvent with an organic co-solvent that
serves multiple
functions (including improving homogeneity of the reaction process and also
providing LTS for
the product formulation), and a catalyst. When these two reactants are mixed
with the solvents
and catalyst, the reaction occurs. An Additive is needed as a Co-solvent to
ensure effective
contact and reaction of the reactants in the initial two-phase mixture in a
high reaction yield,
which also serves as LTS for the final product that is needed for handling and
storage. Finding
an Additive that will work as both a Co-solvent and LTS in this specific
reaction has proven
difficult. The formulation of DTEA HC1 (product) from the reaction must remain
as a
homogenous liquid to provide accurate and simple transfer of the product
without solidification,
phase separation such as solids formation by crystallization (which is a
problem in prior
systems). Aqueous solutions with minimal organic content are preferred in this
process and its
ultimate formulation as they are inexpensive, relatively non-hazardous, and
especially, provide
minimal organic nutrients for microbial growth in end use applications.
Water and LTS used as a Co-solvent
Prior teachings suggest that aqueous propylene glycol (PG) is the reaction
solvent of
choice. However, the product obtained from a PG-based process when diluted
with water
unfortunately forms solids at low temperatures (as defined above) and requires
addition of LTS
to achieve a homogeneous liquid at 32 F to 60 F.
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Brady taught the use of BTS such as 2-phenoxyethanol (PE) and 1-phenoxy-2-
propanol
(PP) with the DTEA HC1 product to provide stable, homogeneous liquids at low
temperature.
These BTS were not used in the reaction but added after the product was
formed. None of the
BTS agents that were found successful by Brady were used or taught as a co-
solvent for the
reaction and, as noted above, have limited application; their use pertains
only to low-water, high-
PG solvent mixtures in DTEA HC1 formulations. It would be more cost effective
and efficient
when LTS is also used as a Co-solvent in the reaction as it eliminates the
need for and cost of
any other co-solvent used strictly for the reaction step, such as propylene
glycol (PG). Thus, in a
streamlined process the formulated product can maintain its low temperature
stability without the
usual operation steps of separating the co-solvent from the reaction mixture
to isolate the Alto
which the LTS is added in a separate formulation step.
The present process uses an Additive that is both a Co-solvent and LTS. This
has the
advantages given below. Determining what Co-solvent that works well for the
present reaction
and is also LTS was neither appreciated nor attempted by the prior art.
However, choice of LTS that is also a good reaction Co-solvent is not a
trivial exercise.
A commonly used and widely preferred GLTS (such as propylene glycol (PP),
glycerol, or
ethylene glycol) are not good as LTS for DTEA HC1. These prior art GLTS do not
function well
or at all in the present process. Neither is an aromatic ring functional group
a sufficient criterion
for selection of LTS as a Co-solvent, e.g., neither benzyl alcohol (BA) nor 1-
phenoxy-2-propanol
(PP) is an effective Co-solvent for the present DTEA HC1 reaction using H202
or azo catalysts in
the present invention, although both are known as excellent GLTS.
The present Additives that are Co-solvents used in the present reaction and
used as LTS,
can be optionally further added to the aqueous DTEA HC1 product solution to
provide a stable
liquid at temperatures down to at least 32 F.
A formulation that forms solids at low temperatures such as these which are
commonly
encountered in storage and use of this product is not practical and is
problematic. When solids
form in a formulation, it is often difficult to regain homogeneity. Storage in
specially heated
storage areas to prevent lower temperatures or using heat and agitation to
melt and re-blend the
mixture is time-consuming, expensive and inconvenient. Heterogeneous mixtures
are difficult to
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pump, can clog nozzles and filters, do not meter well, and cannot be used to
provide consistent or
accurate dosing.
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 wt%. The amount of Additive (LTS/Co-solvent)
used in the
reaction is from about 10 to about 49 wt%, and preferably from about 15 to
about 35 wt%. The
effective Additives are represented by the following Formula A:
Phi-(0),(CH2)t OH
Formula (A)
wherein:
Ph is phenyl;
n is 0 or 1;
k is 2-4; and
m is 1-3.
Representative examples of such Additives of Formula A are PA, PE, and DiEPh.
Some
examples of GLTS found ineffective as Co-solvents are BA, PP and PG. Thus, it
is not apparent
to one skilled in this art what will work as an Additive in the process based
on prior known
reactions.
When carrying out the current reaction, the mixture initially has two liquid
phases;
namely, an organic phase containing decene and an aqueous phase containing
cysteamine HC1
(CA HC1). The latter aqueous phase also contains the catalyst. While not
wishing to be bound
by theory, it is believed that for reaction to occur efficiently, decene must
have sufficient
solubility in or contact with the aqueous phase. The present phenyl alcohol Co-
solvents have a
suitable balance of polar and nonpolar character which facilitates the
required mixing and
solubilization in the reaction. These Co-solvents also possess suitable
properties to solubilize the
final product at low temperatures from about 32 F to about 60 F to avoid
solidification, solids
formation and/or or phase separation as LTS agents. These present LTS are
present in the final
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product solution from about 1 to about 30 wt%, preferably from about 2 to
about 20 wt%. Many
of the prior used solvents do not have such properties and do not provide
these desired results.
Catalyst/Initiator
The present process requires that a free radical initiator is used. When the
Co-solvent is
used with various catalysts/initiators there is the issue of solubility and
which ones will work in
the system. For example, hydrogen peroxide and the azo initiator (including
non-water soluble
azo initiators) are taught by Mariam (discussed above). However, the preferred
azo initiators
that Mariam taught were azobisnitriles which are not water soluble. Mariam
also provided no
data for the azo initiators, which have been found in this present testing
that even water soluble
azo initiators are not effective with PG as the solvent. However,
surprisingly, an azo catalyst
with PE or PA solvent in the present reaction alone resulted in the desired
LTS product.
The present preferred catalysts are azo catalysts that are water soluble such
as:
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).
Selection of these various reaction parameters is not simple to obtain the
desired results.
Even though Brady's results showed 2-phenoxyethanol (PE) and PP to be good BTS
for the
diluted reaction product (added after the reaction was run), and Mariam
teaches that good
reaction solvents are specific glycols and glycol ethers, Mariam did not teach
any of Brady's
claimed BTS as reaction solvents and did not teach any phenyl-substituted
alcohols of Formula
(A). The present results show 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
(present data and Brady), Dowanol DPM (dipropylene glycol methyl ether,
Brady)]. Thus, it is
not apparent to a skilled person how to identify a solvent that is successful
for both purposes, i.e.,
an Additive. Indeed, it was surprising that two structurally similar compounds
taught by Brady as
a good BTS (2-phenoxyethanol (PE) and PP) gave greatly different results as
reaction solvent,
good and poor, respectively. Another solvent which now is identified as an
excellent BTS was
BA; however, it proved to be a poor reaction solvent. Another good Co-solvent
diethylene
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glycol phenyl ether (Dowanol DiEPh) has been found to also be a good LTS for
DTEA HC1.
The present data and observations indicate that successful reaction results
not only depend on the
solvent but also the catalyst. Comparison of data in Tables 1 and 2 show good
results with H202
but poor results with V-50.
If a skilled person were to randomly screen a list of solvents taught by Brady
and other
solvents of similar structure (such as alcohols) with both H202 and V-50 (and
possibly other
commercially available free radical initiators), as well as at varying solvent
concentrations and
with varying amounts of water, the number of combinations to test would be
very large and
require undo experimentation and an impractical amount of time to test, making
the ultimate
selection of successful reaction solvent for this present process not
practical. A method to just
find them by testing is daunting as the list to test would be very large with
multiple conditions
and the reaction actually run to determine what was effective for the desired
results. Thus, this is
not a simple substitution of a few items to see what would work; rather it
requires multiple
variables and undue experimentation to find what is now claimed.
Clearly, previous attempts to make DTEA HC1 have had difficulties obtaining
high
reactant conversion and yields, to have no phase separation, solidification,
or solids formation at
lower temperatures such as 32 F without LTS; to control microbial growth by
limiting organic
components; to not require separation steps of the solvent or product; and to
have ease of
handling with low environmental impact by using a larger portion of an aqueous
based system.
The present process provides these advantages.
This process provides a final product which is formed from the present
reaction as a
solution containing: a) from about 2 to 25 wt% of DTEA HC1, preferably from
about 5 to about
15 wt%, b) additional water and Additive added after the reaction if needed in
an amount from
about 1 to about 30 wt% of Additive, preferably from about 2 to about 20 wt%.
The final
product provides a low temperature stability of at least from 32 F to about 60
F.The invention
will be further clarified by a consideration of the following examples, which
are intended to be
purely exemplary of the invention.
The letter examples are comparative examples. The numbered examples are
directed to
the compounds of the present invention.
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Materials
Decene was purchased from Shell.
DiEPh was obtained from DowDupont.
PE was obtained from Nexeo.
Benzyl alcohol and PA were purchased from Sigma-Aldrich.
PP was obtained from GNS Technologies LLC.
CA HC1 was purchased from Hangzhou Qianjin Technology Ltd.
Water is prepared by reverse osmosis (RO).
V-50 was purchased from Wako.
VA-044 was obtained from Sigma-Aldrich.
H202 was purchased from GFS Chemicals, Inc., as a 50% aqueous solution and
then
diluted to 1.5-1.8% solution with water.
Pure, solid DTEA HC1 was made by the method described in US 5087757 and
isolated by
dilution and crystallization with acetonitrile.
General Reaction conditions
The general present reaction conditions are:
Temperatures from about 25 C to about 120 C (preferably from about 74 C to 77
C
preferred);
Atmosphere is air, nitrogen or argon;
Catalyst concentration from about 0.01 to about 5 wt%, 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 HC1 concentration from about 1 to about 40 wt%, preferably from
about
15 to about 30 wt%;
Water concentration from about 10 to about 49 wt%, preferably from about 15 to
about 35 wt%;
Additive concentration from about 10 to about 49 wt%, preferably from about 15
to
about 35 wt%; and
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Optionally are: 36 wt% HC1 added from about 0.01 to about 1 wt%; DTEA HC1
added
from about 1 to about 5 wt%, preferably from about 0.5 to about 2 wt%.
Preparation of DTEA HC1 and Comparatives
Example 1: General Procedure for H202 as the catalyst
Using 72 g of decene, 62 g of CA HC1, 50-75 g of Co-solvent, 44 g of water,
2.75 g of
DTEA HC1, 26-30 mL of H202, 0.1 mL of concentrated HC1, the following general
process was
run with the various Co-solvents indicated.
To a three necked flask equipped with mechanical stirrer, thermocouple,
addition funnel
and nitrogen inlet, cysteamine HC1, Co-solvent, water and DTEA HC1 were added.
The system
was flushed with nitrogen and the reaction was carried out under the
atmosphere of nitrogen.
The mixture was stirred and heated to 65 C using a water bath. To this mixture
0.1 mL of
concentrated HC1 was added followed by 10 mL of decene. The addition of
hydrogen peroxide
solution was then started along with the remaining decene, maintaining the
reaction temperature
below 80 C (about 74 C to 77 C is preferred). Hydrogen peroxide solution was
added over a
period of 40 min. and decene was added over a period of 20 min. The reaction
mixture was
stirred for another h after completion of the addition of hydrogen peroxide
while maintaining the
reaction temperature below about 80 C (about 74 C to about 77 C temperature is
preferred).
The mixture was cooled and analyzed. The results are shown in the following
Table 1.
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Table 1: DTEA HC1 Process Using Hydrogen Peroxide and Various Co-solvents
Example Co-solvent (g) Aqueous DTEA Unreacted Unreacted Comments
H202 HCI decene % cysteamine
Yield % HCI %
1 Propylene glycol 30 mL 84.4 4 3.5 Reaction
(PG) (1.5% worker
well
in PG
(50.5 g) solution)
2 2- 27 mL 83 Not 3.9 Reaction
Phenoxyethanol (1.85% available worker
well
in PE
(PE) solution)
(75g)
A Benzyl alcohol 27 mL 10 Not a
good
(BA) (1.5% Co-
solvent
for the
solution)
(50.5 g) reaction.
Three layers
were formed
B 1-Phenoxy-2- 30 mL Not 17.8 Not Not a
good
propanol (3.1% analyzed analyzed Co-
solvent
for the
(PP) solution)
reaction.
(75 g) Two
layers
were formed
3 2-Phenylethanol 30 mL Not 1.63 Not Reaction
(PA) (3.1% analyzed analyzed worked
well
in PA
(75 g)
solution)
The presence of two or three layers is evidence of low conversion and yield.
These results show
that PG, PE and PA are effective Co-solvents with H202 catalyst. BA and PP
were not effective
and only produced a low product yield.
Example 2: General Procedure for V-50 as the catalyst
Using 72 g of decene, 62 g of CA HC1, 75 g of Co-solvent, 75 g of water, 2.75
g of
DTEA HC1, 0.39-0.78 g of V-50 [2,2'-Azobis(2-methylpropionamidine)
dihydrochloride] in 10
mL of RO water, 0.1 mL of concentrated HC1, the following general process was
run with the
various Co-solvents indicated.
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To a three necked flask equipped with mechanical stirrer, thermocouple,
addition funnel
and nitrogen inlet, cysteamine HC1, Co-solvent, water and DTEA HC1 were added.
The system
was flushed with nitrogen and the reaction was carried out under an atmosphere
of nitrogen. The
mixture was stirred and heated using a water bath to 65 C. To this mixture 0.1
mL of
concentrated HC1 was added, followed by 10-15 mL of decene. About 5 mL of V-50
solution
was then added and continued the stirring. The remaining decene was added
dropwise to the
reaction mixture over a period of 30-35 min. maintaining the reaction
temperature below 80 C
(74 C to 77 C is preferred). Another portion of V-50 (5 mL) was added after
the addition of
about 50 mL of decene, and continued the stirring. Stirring was continued for
another 1.5-2 h
after completion of the addition of decene while maintaining the reaction
temperature below
80 C (about 74 C to 77 C is preferred). The mixture was cooled and analyzed.
The results are
shown in the following Table 2.
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Table 2: DTEA HC1 Process Using V-50 and Various Co-solvents
Example Co-solvent V-50 (g) DTEA Unreacted Unreacted Comments
(g) HCI decene % cysteamine
Yield HCI %
%
C Propylene glycol 0.78 g in -- PG
is not a
(PG) 10 mL good
(75 g) water solvent
with V-50
catalyst
4 2- 0.39 g in 95 1.5 1.4 Good
Phenoxyethanol 10 mL solvent.
(75 g) water Reaction
(PE) worked
well.
D Benzyl alcohol 0.5 g in 10 BA is
not a
(BA) 10 mL good Co-
(75 g) water solvent.
Three
layers were
formed
E 1-Phenoxy-2- 0.78 g in NA 24 NA PP is
not a
propanol 10 mL good Co-
(PP) water solvent.
(75 g) Two
layers
were
formed
2-Phenylethanol 0.78 g in NA 3.01 NA PA worked
(PA) 10 mL a good
as
(75 g) water PE based
on decene
consumptio
n.
NA = Not Analyzed
These results show that PE and PA were effective as Co-solvents. PG, PP and BA
were
5 not effective.
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Example 3: Comparison of PE and PG
Addition of PE in the range of about 5 wt% to about 10 wt% to a 15 wt% DTEA
solution
(prepared from commercial DTEA HC1 concentrate by diluting with water)
produces
homogeneous solutions at both RT and upon prolonged storage ¨ several days- at
32 F. The
weight percent DTEA HC1 in the solutions after addition of PE ranges from
about 6.5 wt% to
about 7 wt%.
Similarly, addition of PE in the range of about 13 wt% to about 16 wt% to a 15
wt%
DTEA solution (prepared from commercial DTEA HC1 concentrate by diluting with
water)
produces homogeneous solutions at both RT and upon prolonged storage - several
days- at 32 F.
Below approximately 13 wt% PE the solution is homogeneous at RT, but solid at
32 F. The
weight percent DTEA HC1 in the solutions after addition of PE ranges from
about 12.5 wt% to
about 13 wt%.
It should be noted that like the reaction to manufacture DTEA HC1, these
formulations
require a delicate balance between water and organic Additive in order to
maintain homogeneity.
Addition of too much or too little of either can affect the low temperature
stability to
solidification and can also affect homogeneity of the mixture at higher
temperatures due to phase
separation. These studies contain only results in which the solutions remain
homogeneous
throughout the temperature range studied. Only solutions at the lower end of
Additive
concentrations effective as LTS of a given solution were studied. The goal is
to add
approximately the smallest amount of organic LTS that is effective since this
is both
economically and microbially prudent.
In a direct comparison of the effectiveness of PE relative to PG, a 16.7 wt%
DTEA
solution (prepared as described above for 7.5 and 15 wt% solutions) was
diluted with either PE
or PG to provide solutions that contain 13.9 wt% of DTEA HC1 and 16.6 wt% of
either PG or
PE.
Both solutions were homogeneous at RT. The DTEA HC1 formulation containing PE
remained homogenous at 32 F while the DTEA HC1/PG formulation rapidly
solidified and
remained solid.
For further comparison, see Figure 1, the solubility of DTEA HC1 as an
unprocessed
DTEA HC1 Mariam reaction mixture and pure DTEA HC1 solid was determined in
water at
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different temperatures. The Mariam reaction mixture was produced using
hydrogen peroxide
catalyst and PG co-solvent. The mixture contained approximately 50 wt% of DTEA
HC1, 20
wt% of PG, and 30 wt% of water), The pure DTEA HC1 was isolated from a Mariam
reaction
mixture by addition of acetonitrile, cooling the mixture on ice, and
collecting the white DTEA
HC1 solid, which was dried prior to use.
Solids form at 71 F when in the Mariam DTEA HC1 reaction mixture to 20 wt%
DTEA
HC1 by dilution with water. Further dilution with water of the Mariam reaction
mixture to 5 wt%
of DTEA HC1 gives a solution forming solids at an even lower temperature (55
F), see Figure 1.
By comparison, the solubility of pure DTEA HC1 in water is 11 wt% at 67 F and
less than 1 wt%
at 56 F (see Figure 2). PG is a better for solvent than water for DTEA HC1,
but PG does not
provide low-temperature stability (LTS) to the mixtures containing it.
Example 4: Procedure for 2,2'-Azobis[2-(2-imidazolin-2-yl)propanel
dihydrochloride (VA 044)
as the catalyst
The general procedure outlined in Example 2 was followed using 72 g of decene,
62 g of
CA HC1, 75 g of Co-solvent, 75 g of water, 2.75 g of DTEA HC1, 0.6 wt% of VA-
044 in 10 mL
of RO water. No solid DTEA HC1 was added to this reaction. Analysis showed
DTEA HC1 was
produced in 77.4% with 81% conversion in 2 h.
Example 5: Dilution Procedure
Part A: Propylene glycol/Hydrogen peroxide process ¨ dilution with water and 2-
phenoxyethanol
(PE)
DTEA HC1 product mixture (200 g, 50 wt% DTEA HC1) was mixed at RT with 380 g
of
water and 86.6 g of 2-phenoxyethanol (PE) to obtain 666.6 g of 15% DTEA HC1 as
a clear
solution containing 13% of 2-phenoxyethanol (PE). Further 1:1 dilution at RT
with water
provided a 7.5% DTEA HC1 as a clear solution containing 6.5% of 2-
phenoxyethanol (PE).
Part B: 2-Phenoxyethanol/V-50 Process ¨ dilution with water and 2-
phenoxyethanol (PE)
DTEA HC1 product mixture (270 g, 47.4 wt% DTEA HC1) was mixed at RT with 544 g
of water and 39 g of 2-phenoxyethanol (PE) to obtain 853 g of 15% DTEA HC1 as
a clear
solution containing 13% 2-phenoxyethanol (PE) (270 g of the product mixture
had already 72 g
of PE). Further 1:1 dilution at RT with water provided a 7.5% DTEA HC1 as a
clear solution
containing 6.5% of 2-phenoxyethanol (PE).
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Example 6: Crystallization behavior
Part A: Mariam reaction (propylene glycol/hydrogen peroxide process diluted
with water and 2-
phenoxyethanol (PE)
A 15% DTEA HC1 solution containing 13% 2-phenoxyethanol and a 7.5% DTEA HC1
containing 6.5% of 2-phenoxyethanol prepared from the crude product mixture
obtained from
propylene glycol/hydrogen peroxide process (Example 5A above) remained
homogeneous
liquids when the temperature was reduced to 32 F.
Also, a 16.4% solution of DEA HC1 containing 10.34% of PE upon storing in a
refrigerator for two days did not result in any solids precipitation or
crystallization.
As a comparison, this result with may be contrasted with Figure 1 in which
phenoxyethanol was not present and solids formation occurred at 32 F.
Part B: Reaction product from 2-phenoxyethanol/V-50 Process diluted with water
and 2-
phenoxyethanol (PE)
1) A 15% DTEA HC1 solution containing 13% 2-phenoxyethanol prepared from
the
crude product mixture obtained from 2-phenoxyethanol/V-50 process (Example 5B
above) was a
slightly cloudy solution at 32 F. However, no filterable solids were formed at
this temperature.
As a comparison, this result with may be contrasted with Figure 1 in which
phenoxyethanol was not present and solids formation occurred at 32 F.
2) A 7.5% DTEA HC1 solution containing 6.5% 2-phenoxyethanol prepared from
the crude product mixture obtained from 2-phenoxyethanol/V-50 process (Example
5B above)
was a homogeneous liquid at 32 F.
As a comparison, this result with may be contrasted with Figure 1 in which
phenoxyethanol was not present and solids formation occurred at 32 F.
Part C: Purified DTEA HC1 diluted with water and 2-phenoxyethanol (PE)
A first 15% DTEA HC1 solution containing 13% 2-phenoxyethanol and a second
7.5% of
DTEA HC1 containing 6.5% of 2-phenoxyethanol prepared from DTEA HC1 (isolated
by
crystallization of the crude product mixture using acetonitrile) were both
homogeneous liquids at
32 F.
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In contrast, DTEA HC1 is essentially insoluble in water at 32 F and a 15 wt%
DTEA HC1
solution in water forms solids well above RT. (See Figure 2).
Methods of Use of DTEA HC1
The product formed from the present process, DTEA HC1, is used in industrial
water
treatment systems for control of biofouling and corrosion.
Although the invention has been described with reference to its preferred
embodiments,
those of ordinary skill in the art may, upon reading and understanding this
disclosure, appreciate
changes and modifications which may be made which do not depart from the scope
and spirit of
the invention as described above or claimed hereafter. 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.
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