Use of an oil comprising a non-neurotoxic Anti-wear additive

Abstract

To provide use of an anti-wear additive having both a satisfactory anti-wear effect and enabling improvement of a safety level in aviation and other aeroderivative applications.SOLUTION: Use of at least one anti-wear additive in an oil, the at least one anti-wear additive comprising: Wherein each of R1, R2, R3 and R4 is independently selected from an alkyl, O-alkyl, aryl or O-aryl group, and wherein A is a divalent group selected from an alkylene group comprising from 7 to 36 C-atoms or a branched alkylene group comprising from 6 to 36 C-atoms, a mono -, poly - or polyaromatic arylene group or an aralkylene group, and wherein each of X1 and X2 is independently a bond, an oxygen or a nitrogen-atom, and wherein n is an integer in the range of from 1 to 5; For reducing and / or preventing the neurotoxicity of said oil, preferably turbine oil.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to the technical field of anti-wear additives used in oils such as oils for lubricating aircraft or aeroderivative turbines or hydraulic oils. [Background technology]

[0002] Aircraft or aeroderivative turbine engines use synthetic lubricating oils, typically containing an ester base and various antiwear additives from the family of organic phosphates, such as triaryl phosphates. The most commercially used antiwear additive is tricresyl phosphate (TCP), which has unique antiwear properties not found to date. Its triaryl phosphate analogs are also interesting antiwear additives.

[0003] Leaks of lubricating oils, especially those containing tricresyl phosphate or its triaryl phosphate analogues, in aircraft cabin air can occur from worn or defective seals or due to migration of lubricating oil into the cabin air pressurizing system even under normal operating conditions. These recurring leaks have been explained as being due to pressure oscillations between the bearing room and the air circuit caused by normal operating conditions (increasing engine power, takeoff, etc.) (Michaelis S. et al. Public Health Panorama 2017, 3, 2, pp. 198-211). Depending on the situation, the leaks can become very noticeable, usually after bearing failure in the turbine, resulting in visible fume events or white mist in the cabin.

[0004] Aerotoxic syndrome is a pathological condition that combines physical and neurological symptoms caused by the short- and long-term effects of exposure to aircraft cabin air contaminated with hydraulic or engine oil or any other contaminants found as gases and / or aerosols. While reported symptoms are typically nonspecific and cabin air quality monitoring studies indicate contaminant levels below exposure limits and not harmful to human health, the challenge is to continuously and during operation measure the so-called non-gaseous, airborne oil fumes that occasionally deposit and concentrate in various locations throughout the aircraft (Kasper Solbu et al. J. Environ. Monit. 2011, 13, 1393).

[0005] Symptoms similar to those of aerotoxic syndrome can also be observed in terrestrial environments, for example on offshore platforms, in the presence of aeroderivative turbines, which operate similarly to aircraft turbines and implement lubricants with similar compositions, particularly in terms of antiwear agents.

[0006] Nevertheless, numerous studies (Michaelis, S. et al. Public Health Panorama 2017, 3, 2, p. 198-211) have demonstrated a relative causal relationship between acute and / or chronic exposure to substance-containing aircraft cabin air and neurological, neurobehavioral and respiratory symptoms.

[0007] Conventional organophosphate antiwear additives, such as tricresyl phosphate (TCP), particularly its tri-orthocresyl phosphate (ToCP) isomer, are known to have strong neurotoxic effects (Craig P. et al., Journal of Toxicology and Environmental Health Part B: Critical Reviews 1999, 2, 4, pp. 281-300). Beyond the overall toxicity associated with organophosphates, which are widely used in various fields, especially as insecticides and pesticides, one specific and widely recognized reason for this neurotoxic effect is the rapid biotransformation of tricresyl phosphate isomers containing at least one ortho substitution into a metabolite called saligenin, a potent inhibitor of cholinesterase. ToCP poisoning leads to a condition called organophosphate-induced delayed neuropathy (OPIDN), the mechanism of which has been extensively studied. Furthermore, TCP is also known to be a reproductive toxicant.

[0008] As an anti-wear additive, oils containing TCP without ortho isomers have been developed. Nevertheless, despite the absence of ToCP in TCP, the level of cholinesterase inhibition in the serum of rats exposed to TCP is not zero, and although low, it persists (Mackerer CR et al. J. Toxicol. Env. Health Part A 1999 57(5):293-328). Similarly, previous studies have shown problems with spinal cord demyelination resulting from exposure to the meta- and para-forms of TCP (WN Aldridge, Biochemical Journal 1954 56, 185-189).

[0009] Very recent studies have shown that tricresyl phosphate and its triaryl phosphate analogues also act on other biological targets, particularly at the cellular level (AV Terry, Pharmacology and Therapeutics 2012, 134, pp. 355-365; Al Salem et al. Chemosphere 2019, 237, 124519).

[0010] All of these studies and this long history constitute a body of evidence and factors that make tricresyl phosphate and its triaryl phosphate analogue additives particularly concerning. It would appear useful to develop alternative antiwear additives to tricresyl phosphate and its triaryl phosphate analogues in order to increase the safety level of hydraulic oils and oils used in aircraft and aeroderivative turbines.

[0011] Identifying alternative antiwear additives to tricresyl phosphate and its triaryl phosphate analogs is a recognized issue, even if there is not unanimous agreement regarding the need to obviate tricresyl phosphate and its triaryl phosphate analogs.

[0012] To the applicant's knowledge, no research has identified alternative anti-wear additives that have both satisfactory anti-wear effects and proven non-neurotoxicity. For example, recent studies characterizing the potential neurotoxicity of new organophosphates developed and marketed as new generation flame retardants have mostly found levels of risk comparable to those of conventional materials such as TCP (Zhang et al. Neurotoxicology and Teratology 2019, 73, pp. 54-66; Ryan et al. Neurotoxicology 2016, 53, 271-281; ​​Sirenko et al. Toxicolog. Sci. 2019, 167, pp. 58-76). The issue of organophosphate neurotoxicity remains unresolved to this day.

[0013] Furthermore, TCP is also known to be a reproductive toxicant, and the development of an alternative antiwear additive to tricresyl phosphate and its triaryl phosphate analogues, for which the lack of neurotoxicity and reproductive toxicity is established, would be advantageous and would allow for increased safety levels in aviation and other aeroderivative applications.

[0014] Various solutions have been developed in the prior art.

[0015] U.S. Patent Application Publication No. 2016 / 0002565 discloses a tricresyl phosphate-free turbine oil containing at least one base oil, at least one alkyl polyglycoside, and a phenol derivative such as 3,5-di-tert-butyl-hydroxytoluene. The replacement of tricresyl phosphate with a phenol derivative helps prevent aerotoxicity when the oil is used in an aircraft turbine. Nevertheless, the use of such an oil in an aircraft turbine appears unable to provide the same effectiveness as an oil containing tricresyl phosphate, as the formulation described does not contain any agent with antiwear properties that can replace TCP, and the formulation contains a heat-sensitive alkyl polyglycoside.

[0016] To date, only phosphorus compounds have shown effective antiwear effects in aircraft or aeroderivative turbine oils. Without intending to be bound by any theory, this may be related to the fact that phosphorus allows for the formation of a protective layer, commonly referred to as a tribofilm, even at the high temperatures involved in the intended application.

[0017] WO 2010 / 149690 discloses that certain triarylphosphates, in which the phenyl moiety is substituted with one to three isopropyl or tert-butyl moieties, have reduced effects on butyrylcholinesterase, particularly compared to TCP. These inhibitory results imply a possible reduction in neurotoxicity associated with these compounds compared to that observed with TCP. Nevertheless, a simple demonstration of a limited effect on a single cholinesterase does not appear to be sufficient to ensure an adequate level of safety for aviation applications.

[0018] The following documents are also known from the prior art:

[0019] Ike van der Veen et al.'s publication "Phosphorus flame retardants: properties, production, environmental occurrence, toxicity, and analysis," Chemosphere 88 (2012) 119-1153, describes the toxicity of certain phosphorus flame retardants (PFRs). These flame retardants include phosphorus compounds such as resorcinol bis(diphenyl phosphate) (RDP) or bisphenol diphenyl phosphate (BADP). However, this publication is inconclusive because it does not specifically address the neurotoxicity of the flame retardants presented (neurotoxicity is never mentioned or suggested). In addition, it clearly shows that there is little data available regarding the two compounds mentioned above, either related to their toxicity in humans or regarding their ecotoxicity. For example, there is no data related to the acute toxicity of these two compounds. Only reproductive toxicity data is reported, and finally, this publication only describes a limited comprehensive list of toxicity data.

[0020] However, "toxicity" specifically refers to: - reproductive toxicity equivalent to impairment of fertility or alteration of prenatal mammals; - mutagenicity, which is the propensity of a substance to cause genetic mutations; - Acute toxicity is the "toxicity" induced within a short period (for example, 24 hours) by the administration of a single (possibly large) dose or several doses taken within a short period of time of a toxic product or mixture (natural or chemical); - Ecotoxicity, which is all the imbalances or nuisances caused by industrial activities or the placement of foreign substances or products in the natural environment; - Neurotoxicity, which is the ability of a substance or compound to have adverse effects on the nervous system of a mammal, such as a human. It is a fairly broad concept that includes:

[0021] However, a compound may, for example, not be a reproductive toxicant, show no signs of acute toxicity, or even exhibit CMR (carcinogenic, mutagenic, or toxic to reproduction) properties to human health, yet be highly neurotoxic (or vice versa).

[0022] As an example, however, the present applicant has demonstrated that the tetrakis(2-chloroethyl)dichloroisopentyl diphosphate compound (V6), described in a publication by Ike van der Veen et al. as non-neurotoxic, non-mutagenic, and not causing significant skin irritation, is ultimately highly neurotoxic. Specifically, the latter compound V6 has a neurotoxicity rating of 91% in QSAR modeling studies (described below) and belongs to cluster 4 in spherical harmonics 3D modeling studies (also described below). This reinforces the fact that the definition of "toxicity" is not strict and that a compound can quite easily be considered as having no CMR properties or acute toxicity and as being highly neurotoxic, and vice versa.

[0023] Document WO 2015 / 026566 describes a lubricating oil comprising (i) a major amount (50% by weight or more, based on the total weight) of a natural or synthetic base oil and (ii) a minor amount of an aryl bisphosphate ester of formula (I) as an anti-wear additive and which may correspond, for example, to resorcinol bis(diphenyl phosphate).

[0024] Document EP 0 612 837 describes polyphenylene ether-based lubricating oils containing anti-wear additives comprising hydrocarbyl bis(dihydrocarbyl phosphate) compounds, such as resorcinol bis(diphenyl phosphate).

[0025] Document U.S. Pat. No. 5,560,849 describes a lubricating composition comprising a base oil, which may be a polyol ester or a phosphate ester such as tricresyl phosphate, and an aryl diphosphate ester having antiwear properties (column 2, lines 11-35).

[0026] Document U.S. Patent Application Publication No. 2001 / 306530 describes compositions comprising a base oil, which may be a polyol ester, and a phosphorus compound. The phosphorus-based compounds exemplified include a diphosphorus compound ("tetraphenyl(m-phenylene)bisphosphate") and tricresyl phosphate.

[0027] Even though there is no unanimous agreement in the prior art regarding the need to obviate tricresyl phosphate and its triaryl phosphate analogs, there is a need to develop alternative antiwear additives to tricresyl phosphate and its triaryl phosphate analogs.

[0028] There is a particular need in the prior art to develop alternative anti-wear additives that have both satisfactory anti-wear effectiveness and enable increased safety levels in aviation and other aeroderivative applications. Summary of the Invention [Problem to be solved by the invention]

[0029] In that context, the applicant has shown that polyphosphorus compounds, in particular aryl polyphosphorus compounds, having satisfactory or improved anti-wear and thermal stability properties, have significantly reduced or no neurotoxicity compared to the neurotoxicity of monophosphate anti-wear derivatives such as TCP, and can therefore be advantageously used in oils, in particular for lubricating aircraft or aeroderivative turbines, to reduce and / or prevent neurotoxicity in oils, in particular turbine oils. The anti-wear properties of some polyphosphate compounds, which are aryl diphosphates, have been shown, for example, in the prior art, inter alia, in WO 96 / 20263, US 2012 / 0329693, WO 2012 / 015873, EP 0612837 and WO 2015 / 026566 or in the publication Zhao et al. Ind. Eng. Chem. Res. 2013, 52, 22, 7419-7424.

[0030] Therefore, they can be advantageously used for the prevention of aerotoxicity syndrome, especially in the case of fume events. The use of polyphosphorus compounds such as aryl diphosphates as antiwear additives has already been considered in the prior art, but to the applicant's knowledge, no studies have been able to demonstrate their non-neurotoxicity and therefore their interest in preventing aerotoxicity syndrome. Furthermore, the applicant has also demonstrated the lack of reproductive toxicity of polyphosphorus compounds, which solidifies their interest as a replacement for TCP as an antiwear agent in oils such as hydraulic oils or turbine oils. [Means for solving the problem]

[0031] The present invention also relates to the use of at least one anti-wear additive in an oil, said at least one anti-wear additive being represented by formula (I) [ka] (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from a linear alkylene group containing 7 to 36 carbon atoms or a branched alkylene group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; Each of X1 and X2 independently represents a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5. to reduce and / or prevent the neurotoxicity of said oil. Including, relating to use.

[0032] Preferably, the oil and / or at least the anti-wear additive does not contain tricresyl phosphate or its triaryl phosphate analogue.

[0033] The polyphosphorus compounds of formula (I) can therefore be used to obtain non-neurotoxic oils or oils with reduced neurotoxicity.

[0034] The compounds of formula (I) have interesting anti-wear properties that can be compared with those of their triaryl phosphate analogues of tricresyl phosphate. They also exhibit a very low or zero risk level in terms of neurotoxicity, thus reducing and / or preventing the neurotoxicity of the oils in which they are incorporated.

[0035] Specifically, as demonstrated by the experimental tests described below, the applicant has unexpectedly discovered that certain compounds of formula (I) above are non-toxic, non-neurotoxic, or even non-reproductively toxic in terms of their effect on cholinesterase.

[0036] The present invention also relates to the use of at least one anti-wear additive in an oil, said at least one anti-wear additive being represented by formula (I) [ka] (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from an alkyl group containing 7 to 36 carbon atoms or a branched alkyl group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; Each of X1 and X2 independently represents a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5. for the prevention of aerotoxicity syndrome, preferably in the case of a fume event.

[0037] Also preferably, for this use, the oil and / or at least the antiwear additive does not comprise tricresyl phosphate or one of its triaryl phosphate analogues. Of course, the various features, variations and embodiments of the invention can be related to each other in various combinations, provided that they are not incompatible or mutually exclusive.

[0038] In the present invention, unless otherwise specified, the term "comprise" and its derivatives should be understood as not limiting or excluding the presence of other components or steps. In some particular embodiments, the term "comprise" can be understood as "essentially consist of" or "consist of."

[0039] Unless otherwise stated, intervals stated in the present invention are understood to be inclusive. [Brief explanation of the drawings]

[0040] [Figure 1] Shown are molecules resulting from a spherical harmonic modeling exercise. The compounds in the top row belong to cluster 1, and the compounds in the bottom row belong to cluster 3. [Figure 2-9] 1 is a table summarizing the results of tests carried out to study the neurotoxicity of phosphorus-based compounds according to the prior art (comparison compounds) and of compounds of formula (I) according to the present invention (compounds 1-10). DETAILED DESCRIPTION OF THE INVENTION

[0041] A first object of the present invention is the use of at least one anti-wear additive in an oil, said at least one anti-wear additive being represented by formula (I) [ka] (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from an alkylene group containing 7 to 36 carbon atoms or a branched alkylene group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; Each of X1 and X2 independently represents a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5. for reducing and / or preventing the neurotoxicity of said oil, preferably turbine oil.

[0042] The expression "to reduce" the neurotoxicity of an oil means that the compounds of formula (I) according to the invention are capable of and / or are configured to reduce the neurotoxicity of the oil into which they are incorporated, i.e. by their presence (generally in the majority), in particular relative to other conventional anti-wear compounds which are generally neurotoxic; the compounds of formula (I) make it possible to lower / reduce the neurotoxicity of the oil and to obtain a non-neurotoxic oil or at least an oil of reduced toxicity.

[0043] The expression "to prevent" the neurotoxicity of an oil means that the compound of formula (I) makes it possible to prevent the oil from being considered a neurotoxin and / or to prevent the appearance of neurotoxic symptoms in a mammal, such as a human or animal, that will come into contact with said oil; these neurotoxic symptoms can, for example, reach the central nervous system (CNS) and have the following effects: headache, loss of appetite, drowsiness, mood and personality disorders, cognitive dysfunction (learning and concentration disorders), or reach the peripheral nervous system (PNS) and have the following effects: movement disorders, such as weakness, tremors, incoordination, convulsions, etc., or sensory damage, such as loss of hearing, color vision, tinnitus, loss of emotional stability, etc.; these effects may or may not be reversible depending on the degree of acute or chronic exposure of the mammal.

[0044] The term "neurotoxicity" refers to the ability of a substance or compound to adversely affect the nervous system of a mammal, such as a human. The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is located in the cranial cavity and spinal cord. It includes the brain, brainstem, and spinal cord. Its role is to receive, record, and interpret signals from the periphery, which then organizes a response to be sent. The PNS consists of ganglia, sensory nerves, which are responsible for transmitting sensations, such as pain, to the brain, and motor nerves, which are responsible for movement by stimulating muscles. They circulate information between the CNS and organs. Therefore, according to the present invention, neurotoxic substances or compounds typically act by distributing or neutralizing nerve impulses, particularly by acting on synaptic emitters or receptors or on enzymes acting on synaptic emitters or receptors, such as cholinesterases. In biochemistry, cholinesterases are enzymes that catalyze the hydrolysis of choline esters (acetylcholine, butyrylcholine) into choline and acetate or butyrate. In physiology, this response is necessary to allow cholinergic receptors to return to their resting state after activation.

[0045] In the present application, the Applicant has unexpectedly and surprisingly demonstrated that certain specific polyphosphorus compounds of formula (I) above are both weakly neurotoxic or completely non-neurotoxic, while at the same time possessing excellent anti-wear properties particularly suited to the demanding field of aviation. This latter quality therefore makes it possible to reduce and / or prevent and / or avoid the neurotoxicity of the oils into which they are incorporated.

[0046] These tests also show that the compounds of formula (I) selected by the Applicant are not random and have a different technical effect (i.e. they make it possible to reduce / prevent / avoid the neurotoxicity of oils) compared to other anti-wear compounds, in particular compared to other (poly)phosphorus anti-wear compounds.

[0047] For the present invention, the applicant has demonstrated the non-neurotoxicity of certain compounds of formula (I) both by in vitro experiments on cholinesterase and by modeling studies (3D molecular modeling with spherical harmonics and QSAR modeling for neurotoxicity and for reproductive toxicity).

[0048] Preferably, IC 50 The 50% inhibitory concentration of the at least one compound of formula (I) on the biological activity of the acetylcholinesterase (AChE) enzyme, referred to as hAChE, is 15 mg / L or more, preferably 16 mg / L or more, and the IC 50 The activity with respect to the butyrylcholinesterase enzyme, termed eqBuChE, is preferably 15 mg / L or more, in particular 50 mg / L or more, preferably 55 mg / L or more, in particular 60 mg / L or more, typically 70 mg / L or more.

[0049] According to the present invention, an IC 50 Values ​​of 15 mg / L or greater for hAChE include the following values ​​and all intervals between these values: 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40, etc.

[0050] Also, according to the present invention, IC 50 Values ​​of 15 mg / L or greater for eqBuChE include the following values ​​and all intervals between these values: 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40; 45; 50; 55; 60; 65; 70; 75; 80; 85; 90; 95; 100; 105; 110; 115; 120; 125; 130; 135; 140; 145; 150; 155; 160, etc.

[0051] Advantageously, the compound of formula (I) belongs to cluster 3 as determined according to molecular modeling with spherical harmonics as described in the publication "Benchmarking of HPCC: A novel 3D molecular representation combining shape and pharmacophoric descriptors for efficient molecular similarity assessments", Karaboga et al. 2013 Journal of Molecular Graphics and Modelling 41;20-30.

[0052] According to another feature of the invention, the compounds of formula (I) have a percentage value (%) from quantitative structure-activity relationship (QSAR) modelling of less than or equal to 0.70%, preferably less than or equal to 0.50%, typically less than or equal to 0.15% for determining neurotoxicity (neurotoxicity QSAR) and less than or equal to 1.5%, preferably less than or equal to 1.15%, typically less than or equal to 0.55% for determining reproductive toxicity (reproductive toxicity QSAR).

[0053] According to the present invention, values ​​of 0.70% or less for neurotoxicity QSAR modeling include the following values ​​and their values: 0.70; 0.69; 0.68; 0.67; 0.66; 0.65; 0.64; 0.63; 0.62; 0.61; 0.60; 0.59; 0.58; 0.57; 0.56; 0.55; 0.54; 0.53; 0.52; 0.51; 0.50; 0.49; 0.48 ;0.47;0.46;0.45;0.44;0.42;0.40;0.38;0.36;0.34;0.32;0.30;0.28;0.26;0.24;0.22;0.20;0.18;0.16;0.14;0.12;0.10;0.09;0.08;0.07;0.06;0.005;0.04;0.03;0.01;0.00.

[0054] Also in accordance with the present invention, values ​​of 1.50% or less for reproductive toxicity QSAR modeling include the following values ​​and all intervals between these values: 1.50; 1.48; 1.46; 1.44; 1.42; 1.40; 1.38; 1.36; 1.34; 1.32; 1.30; 1.28; 1.26; 1.24; 1.22; 1.20; 1.18; 1.16; 1.14; 1.12; 1.10; 1.08; 1.06; 1.04; 1.02; 1.00; 0.80; 0.60; 0.50; 0.40; 0.30; 0.20; 0.10; 0.00.

[0055] Thus, the compounds of formula (I) according to the invention have a risk level in terms of neurotoxicity that is very low and generally corresponds to a score of 0 or to a score of 1 (very low or no risk of neurotoxicity), preferably a score of 0.

[0056] The risk levels as defined above and also exemplified in the experimental section below are very comprehensive and encompass all the data obtained by the various neurotoxicity studies mentioned above, and therefore encompass both in vitro and 3D modeling studies.

[0057] In particular, the risk level is determined by the following tests: - In vitro acetylcholinesterase (AChE) inhibition test, - In vitro butyrylcholinesterase (BuChE) inhibition test, - Cluster types that take into account the shape and function of spherical harmonics (3D modeling), - semi-empirical prediction of neurotoxicity, and - Semi-empirical prediction of reproductive toxicity Take all of the above into consideration.

[0058] By "oil" is meant in the present invention any organic substance, especially any hydraulic oil or turbine oil, that is prone to producing contamination in the passenger compartment in the form of gases and / or aerosols. In some embodiments, the oil is selected from the group consisting of oils for aircraft or aeroderivative turbines, helicopter transmission oils and weapons fluids. Preferably, in the present invention, the oil is an oil for aircraft or aeroderivative turbines.

[0059] The oil is preferably used to lubricate aircraft or aeroderivative turbines.

[0060] As stated above, the groups R1, R2, R3 and R4 of the polyphosphorus compounds of formula (I) according to the present invention are independently selected from alkyl, O-alkyl, aryl, or O-aryl groups.

[0061] An "alkyl group" according to the present invention (unless otherwise specified) is a group having 1 to 36 carbon atoms (C1 to C 36 ), more preferably 1 to 18 carbon atoms (C1 to C 18 ), especially those with 1 to 10 carbon atoms (C1 to C 10 ), typically refers to a linear or branched saturated hydrocarbon group containing 1 to 4 carbon atoms (C1-C4). Examples of alkyl groups according to the present invention include methyl, ethyl, propyl, isopropyl, n-butyl and tert-butyl groups.

[0062] According to the present invention, the alkyl group may optionally be a substituted alkyl group.

[0063] According to the present invention, the expression "substituted alkyl group" denotes a linear or branched saturated hydrocarbon chain as defined above and substituted at one or more of its atoms with one or more groups selected from an OH hydroxyl group, an NH amine group or an NHR primary amine group, where R is an alkyl or aryl group, preferably an OH hydroxyl group. Thus, the alkyl group cannot be substituted with a halogen, such as chlorine.

[0064] By "O-alkyl group" is meant an alkyl group, as defined above, attached to the remainder of the molecule (here, generally a phosphorus atom) through an oxygen atom.

[0065] "Aryl group" means a monovalent aromatic moiety containing 5 to 14 carbon atoms and derived from an aromatic hydrocarbon, such as an aromatic hydrocarbon ring (e.g., phenyl) or two fused aromatic hydrocarbon rings (e.g., naphthyl).

[0066] According to the present invention, aryl groups can be substituted or unsubstituted.

[0067] According to the present invention, a "substituted aryl group" is a group having one or more of its atoms C1-C 18 alkyl group, OH hydroxyl group, NH2 amine group or R is C1-C 18 NHR is an alkyl or aryl group, and at least one substituent consisting of a primary amine group, preferably a C1-C, such as a methyl group. 18 It refers to one ring or two substituted aromatic hydrocarbon fused rings substituted with alkyl groups or OH hydroxyl groups.

[0068] "O-aryl group" means an aryl group, as defined above, attached to the remainder of the molecule via an oxygen atom.

[0069] In some embodiments, at least one of R1, R2, R3, and R4 is alkyl or O-alkyl. In this configuration, preferably each alkyl group has 1 to 22 carbon atoms (C1 to C4). 22), preferably 1 to 18 carbon atoms (C1 to C 18 ), especially those with 1 to 10 carbon atoms (C1 to C 10 ), typically an alkyl group containing 1 to 4 carbon atoms (C1 to C4).

[0070] In some preferred embodiments, at least one of R1, R2, R3, and R4 is an aryl or O-aryl group. Preferably, at least two of R1, R2, R3, and R4 are aryl or O-aryl groups. In particular, R1, R2, R3, and R4 are four aryl or O-aryl groups, such as O-phenyl, or substituted O-aryl groups, such as O-dimethylphenyl.

[0071] In some embodiments, at least one of R1, R2, R3, and R4 is a phenyl group. Preferably, R1, R2, R3, and R4 are phenyl groups. R1, R2, R3, and R4 are typically unsubstituted phenyl groups or phenyl groups substituted with at least one methyl group, preferably two methyl groups (e.g., 2,6-dimethylphenyl).

[0072] In some embodiments, at least one of R1, R2, R3, and R4 is an O-phenyl group. Preferably, R1, R2, R3, and R4 are O-phenyl groups. R1, R2, R3, and R4 are typically unsubstituted O-phenyl groups or O-phenyl groups substituted with at least one methyl group, preferably two methyl groups (e.g., 2,6-dimethylphenyl).

[0073] In general, "A" in formula (I) according to the present invention may be selected from an alkylene group, an arylene group, or an aralkylene group.

[0074] An "alkylene group" means (unless otherwise specified) an alkylene group having 7 to 36 carbon atoms (C7-C 36 ), preferably 7 to 22 carbon atoms (C 22 ), preferably 7 to 18 carbon atoms (C 18), or (unless otherwise specified) preferably 6 to 36 carbon atoms (C 36 ), preferably 6 to 22 carbon atoms (C6 to C 22 ), preferably 6 to 18 carbon atoms (C 18 ), especially those with 6 to 12 carbon atoms (C6 to C 12 ) means a branched saturated hydrocarbon divalent group containing

[0075] An alkylene group can be unsubstituted or optionally substituted.

[0076] A "substituted alkylene group" is a linear or branched C1-C alkylene group in which one or more of its atoms are substituted. 18 "substituted alkylene group" refers to an alkylene group as defined above substituted by at least one substituent selected from the group consisting of an alkyl group; an OH hydroxyl group; an NH amine group or an NHR primary amine group where R is an alkyl group (as defined above) or an aryl group (as defined above); an O-phosphate group, such as an O-diphenylphosphate group OP(=O)(OPh)2, and a halogen atom, such as fluorine. Typically, a "substituted alkylene group" refers to a linear or branched C1-C 18 It is substituted with at least one substituent selected from the group consisting of an alkyl group; an OH hydroxyl group; and an O-phosphate group, such as an O-diphenylphosphate group OP(=O)(OPh)2. Thus, an alkylene group substituted with an O-phosphate group may correspond to a 1,3-(2-ethyl-2-[methyl-O-diphenylphosphate])propyl group.

[0077] The term "arylene group" refers to a monocyclic or polycyclic aromatic carbon group derived from an aromatic hydrocarbon and containing at least two (divalent) anchoring points bonded to X1 and X2 located on the aromatic ring (the two anchoring points may be on the same ring in a polycyclic group). Each aromatic or polycyclic aromatic ring may contain 5 to 14 atoms. An arylene group may correspond, for example, to an aromatic hydrocarbon ring (e.g., phenylene), to two fused aromatic hydrocarbon rings (e.g., naphthalene), or to two aromatic hydrocarbon rings connected by a covalent bond between two different atoms belonging to each of the rings. According to a feature of the present invention, the aromatic ring may optionally be interrupted by one or more heteroatoms, which may be selected, in particular, from the group consisting of nitrogen, oxygen, and sulfur atoms, preferably oxygen or sulfur atoms. Preferably, an arylene group does not contain a nitrogen atom within the monocyclic or polycyclic aromatic carbon group. Therefore, in general, an arylene group cannot correspond, for example, to pyridine or pyrimidine.

[0078] Each ring can be unsubstituted or substituted to form a "substituted arylene group."

[0079] A "substituted arylene group" is a group in which one or more of its atoms is C1 to C 18 OH: a hydroxyl group; NH: a primary amine group or NHR: a primary amine group where R is an alkyl group or an aryl group; an O-phosphate group, such as an O-diphenylphosphate group OP(=O)(OPh)2, which may be substituted on one of the rings of a polycyclic group; and an arylene group as described above, substituted by at least one substituent selected from the group consisting of halogen atoms, such as fluorine and excluding chlorine. According to one feature of the present invention, the arylene group preferably comprises at least one C1-C 18 and more preferably, the arylene group is substituted with at least one C1-C2 alkyl group, a hydroxyl group, or at least one O-diphenylphosphate group OP(=O)(OPh). 18The substituted arylene group may be substituted with an alkyl group or at least one O-diphenylphosphate group OP(=O)(OPh). Thus, the substituted arylene group may correspond to an O-diphenylphosphate group, such as a 1,3-(5-O-[(diphenyl)phosphate)]phenyl group.

[0080] If the arylene group is a polycyclic group in which at least two rings are linked by at least one covalent bond between two different atoms, each belonging to one of the rings, the covalent bond between the at least two rings can be interrupted by at least one alkylene group, such as a C(CH) or C(CH) group, a carbonyl group -CO-, a heteroatom or heteroatom group, such as an oxygen atom, a sulfur atom, an NH or NR amine group, a sulfite group OS(=O)O, a sulfone group -S(O)- or a linear or branched perfluorinated group containing, for example, three carbon atoms, such as C(CF) when the polycyclic group contains three rings.

[0081] Examples of monocyclic arylene groups include, inter alia, phenylene groups (C6H4).

[0082] When A is or contains a monocyclic arylene group such as phenylene or a thiophene derivative, X and X are preferably on opposite sides, especially in the 1,4-positions, when the monocyclic arylene group contains 6 carbon atoms (e.g., phenylene). A is preferably an optionally substituted 1,4-phenyl group.

[0083] In particular, when A is phenylene, X1 and X2 are not in the ortho or meta positions unless at least one, and preferably all, of the R1, R2, R3 and R4 groups is an O-phenyl group substituted with two methyl groups, especially in the 2,6-positions, in which case X1 and X2 may be in the meta positions.

[0084] Also, when A is a phenylene group substituted with an O-diphenylphosphate group OP(=O)(OPh)2, preferably X1 and X2 are in the 1,3-positions so as to obtain a 1,3-(5-O-[(diphenyl)phosphate)]phenyl group.

[0085] When A is or includes a polycyclic group, or a polyaromatic group containing, for example, two fused rings, such as a naphthalene group, X1 and X2 are preferably located on opposite sides to maximize the distance between X1 and X2.

[0086] In particular, when A is naphthalene, X1 and X2 are not in the ortho or meta positions (especially in the 1,3-positions), but may be in the 1,4 or 2,7 positions.

[0087] Preferably, group A does not contain electron-withdrawing groups or atoms such as chlorine, carbonyl functions (aldehyde, carboxylic acid, C(O)—O), one or more nitrogen atoms within a carbocyclic or polycyclic group (pyridine or pyrimidine), etc. Thus, group A cannot be a pyridine or pyrimidine.

[0088] Examples of polycyclic arylene groups include 4,4'-biphenyl, 4,4'-diphenylthioether, 4,4'-diphenylether, 4,4'-diphenylphenylethylidene, 4,4'-dimethyldiphenylmethylidene, 4,4'-diphenylsulfone, 4,4'-benzophenone, 2,2'-benzophenone, 1,4-naphthalene, 1,3-naphthalene, 2,7-naphthalene, 2,6-anthracene, 9,10-anthracene, and phenanthrene.

[0089] "Aralkylene group" means an alkyl group covalently bonded to an aryl group and containing two (divalent) anchoring points, located on the alkyl group and / or on the aryl group.

[0090] Similarly, an "aralkylene" group may be substituted or unsubstituted. A "substituted aralkylene" group is one in which one or more of its atoms is C1-C6. 18It means an aralkylene group as defined above substituted by at least one substituent selected from the group consisting of an alkyl group, an OH hydroxyl group; an NH amine group or an NHR primary amine group where R is an alkyl or aryl group; an O-phosphate group, such as the O-diphenylphosphate group OP(=O)(OPh) and a halogen atom, such as fluorine (except chlorine). Preferably, the aralkylene group is a C1-C 18 It is substituted with a substituent selected from the group consisting of an alkyl group, an OH hydroxyl group, and an O-phosphate group, such as an O-diphenylphosphate group OP(=O)(OPh)2.

[0091] Examples of aralkylene groups include, inter alia, 4,4'-[diphenyl(dimethyl)methylidene] and 4,4'-diphenylhexafluoropropane groups.

[0092] In some embodiments, A is 1,4-phenyl, 4,4'-biphenyl, 4,4'-diphenylthioether, 4,4'-diphenylether, 1,3-(5 O-[(diphenyl)phosphate)]phenyl, 1,3-(2-ethyl-2-butyl)propyl, 1,3-(2-ethyl-2-[methyl-O-diphenylphosphate])propyl, 4,4'-[diphenyl(dimethyl)-methylidene], 2,2'-benzophenone, 2,7-naphthalene, 1,2-ethyl, 4,4'-[diphenylphenylethylidene], 4,4'-diphenylsulfone, 4,4'-diphenyl-hexafluoropropane, 1,4-[ (2-phenyl)phenyl], 1,4-[(2,5-di-tert-butyl)phenyl], 1,4-[(2-chloro)phenyl], 4,4'-benzophenone, 1-hydroxy-3-thiophenyl, 1,6-hexyl, 1,4-naphthalene, 2,6-anthracene, 9,10-anthracene, 1,10-decyl, 1,12-n-dodecyl, 2,5-dimethyl-2,5-hexyl, 1,12-dodecyldodecyl, and 1,3-naphthalene groups.

[0093] In some preferred embodiments, A is selected from the group consisting of 1,4-phenyl, 4,4'-biphenyl, 4,4'-diphenylthioether, 4,4'-diphenylether, 1,3-(5 O-[(diphenyl)phosphate)]phenyl, 1,3-(2-ethyl-2-butyl)propyl, 1,3-(2-ethyl-2-[methyl-O-diphenylphosphate])propyl, 4,4'-[diphenyl(dimethyl)methylidene], 2,2'-benzophenone, 2,7-naphthalene, and 1,2-ethyl groups.

[0094] In some more preferred embodiments, A is selected from the group consisting of 1,4-phenyl, 4,4'-biphenyl, 4,4'-diphenylthioether, 4,4'-diphenylether, 1,3-(5 O-[(diphenyl)phosphate)]phenyl, 1,3-(2-ethyl-2-butyl)propyl, and 1,3-(2-ethyl-2-[methyl-O-diphenylphosphate])propyl groups.

[0095] In particular, A is selected from the group consisting of 4,4'-diphenylthioether, 4,4'-diphenylether, 1,3-(5 O-[(diphenyl)phosphate)]-phenyl, 1,3-(2-ethyl-2-butyl)propyl, 1,3-(2-ethyl-2-[methyl-O-diphenylphosphate])propyl groups.

[0096] In certain embodiments, A is an optionally substituted alkyl group, a substituted monocyclic arylene group, or a polycyclic arylene group wherein at least two rings are connected by at least a covalent bond between two different atoms, each belonging to one of the rings, and the covalent bond between the two rings is interrupted by at least one heteroatom or heteroatom group.

[0097] "Halogen atom" means (unless otherwise specified) an atom selected from the group consisting of chlorine, bromine, fluorine and iodine.

[0098] Each of X1 and X2 is independently selected from the group consisting of a single bond, an oxygen atom, and a nitrogen atom, preferably a single bond or an oxygen atom. In some preferred embodiments, X1 and X2 are two oxygen atoms; in other embodiments, X1 and X2 are two nitrogen atoms; and finally, in a final embodiment, one of X1 and X2 is an oxygen atom and the other of X1 and X2 is a nitrogen atom.

[0099] When X1 or X2 is a nitrogen atom, it may be in the form of an NH or NR group, where R is an alkyl or aryl group.

[0100] When X1 or X2 is a single bond, this means that A is directly attached to the phosphorus atom of the P(=O)R1R2 or P(=O)R3R4 group by just one single bond.

[0101] n is an integer between 1 and 5, and n may in particular be equal to 1, 2, 3, 4, or 5. In some embodiments, "n" is 1. When the value of n is not explicitly specified, the polyphosphorus compound refers to at least one oligomer containing 1 to 5 -X1-A-X2-P(O)R4- units, or any mixture of at least two of these. For example, it can be a mixture of oligomers containing 1 to 3 -X1-A-X2-P(O)R4- units. Preferably, n=1.

[0102] In some embodiments, the polyphosphorus compounds used in accordance with the present invention are aryl diphosphates, i.e., they are such that X1 and X2 are two oxygen atoms and each of R1, R2, R3 and R4 is an O-aryl group (as defined above) optionally substituted, for example, with two methyl groups.

[0103] Surprisingly, the non-toxicity, in particular non-neurotoxicity and non-reproductive toxicity, of the polyphosphorus compounds of formula (I) has been demonstrated by the applicant.

[0104] The antiwear properties of some polyphosphorus compounds, including aryl diphosphates, are known in the art and have been previously demonstrated. Thus, polyphosphorus compounds, particularly aryl polyphosphorus compounds, have attractive antiwear effectiveness at least as good as that achieved with conventional antiwear additives such as TCP.

[0105] Preferably, the oil and / or the at least one anti-wear additive does not include tricresyl phosphate or one of its triaryl phosphate analogues.

[0106] The expression "tricresyl phosphate-free oil" refers to an oil in which the amount of tricresyl phosphate, regardless of its substitution type (ortho, meta, para), is below the detection limit of common analytical techniques, such as gas chromatography-mass spectrometry. Suitable techniques for detecting tricresyl phosphate in oil are described, for example, in De Nola G. et al., J. Chromatogr. A 2008;1200(2), pp.211-216.

[0107] In some embodiments, the oils used in accordance with the present invention or the antiwear agents used in accordance with the present invention are substantially free, preferably free, of any aryl monophosphate antiwear additives. In some embodiments, the oils used in accordance with the present invention or the antiwear agents used in accordance with the present invention are substantially free, preferably free, of organic phosphate antiwear additives other than the polyphosphate compound additive.

[0108] In some embodiments, the oils used in accordance with the present invention or the antiwear agents used in accordance with the present invention are substantially free, preferably free, of antiwear additives other than the polyphosphorus compound additive.

[0109] Generally, the antiwear agents according to the invention of general formula (I) represent from 50% to 100% by weight, preferably from 80% to 100%, in particular from 90% to 100% by weight, typically 100%, relative to the total mass of antiwear agents present in the oil.

[0110] According to the present invention, "50% to 100%" means the following values ​​or any interval between these values: 50; 55; 60; 65; 70; 75; 80; 85; 90; 95; 100.

[0111] In one embodiment, the polyphosphorus compound in the oil used in accordance with the present invention is - hydroquinone bis(diphenyl phosphate) HDP, - 4,4'-dihydroxybiphenyl bis(diphenyl phosphate) and its oligomers, - 4,4'-dihydroxydiphenylthioether bis(diphenylphosphate), - 4,4'-dihydroxydiphenyl ether bis(diphenyl phosphate), - 1,3,5-phloroglucinol tris((diphenyl phosphate)), - 2-butyl 2-ethyl 1,3-propanediol bis(diphenyl phosphate), - Trimethylolpropane tris(diphenyl phosphate), 4,4'-dihydroxydiphenylphenylethylidenebis(diphenylphosphate), - 4,4'-dihydroxydiphenylsulfone bis(diphenylphosphate), - 4,4'-dihydroxybenzophenone bis(diphenyl phosphate), - 2,2'-dihydroxybenzophenone bis(diphenyl phosphate), - 4,4'-dihydroxydiphenylhexafluoropropane bis(diphenyl phosphate), - 1,4-dihydroxynaphthalenebis(diphenylphosphate), - 1,3-dihydroxynaphthalenebis(diphenylphosphate), - 2,7-dihydroxynaphthalenebis(diphenylphosphate), - ethanolamine diphenyl phosphate diphenyl phosphoramidate, - 4,4'-diaminodiphenyl ether bis(diphenylphosphoramidate), 2,6-dihydroxyanthracenebis(diphenyl phosphate), 9,10-dihydroxyanthracenebis(diphenyl phosphate), 1,4-dihydroxy[(2-phenyl)phenyl]bis(diphenylphosphate), 1,4-dihydroxy[(2,5-diterbutyl)phenyl]bis(diphenylphosphate), - 1,4-dihydroxy[(2-chloro)phenyl]bis(diphenylphosphate), - 1,3-dihydroxythiophene bis(diphenyl phosphate), - 1,6-hexanediol bis(bis(diphenyl phosphate), 1,10-decanediol bis(diphenyl phosphate), - 2,5-dimethyl 2,5-hexanediol bis(diphenyl phosphate), 1,12-n-dodecanediol bis(diphenyl phosphate), - tetrakis(2,6-dimethylphenyl)-m-phenylene bisphosphate, - tetrakis(2,6-dimethylphenyl)-p-phenylene bisphosphate, - phenylhydroquinone bis(diphenyl phosphate) DPP, - tert-butylhydroquinone bis(diphenyl phosphate), 2,5-di-tert-butylhydroquinone bis(diphenyl phosphate), - 1,4-dihydroxynaphthalenebis(diphenylphosphate), - 2,7-dihydroxynaphthalenebis(diphenylphosphate), - 4,4'-dihydroxybenzophenone bis(diphenyl phosphate), - bis(4-hydroxyphenyl)sulfonebis(diphenylphosphate), 4,4'-(hexafluoroisopropylidene)bis(diphenyl phosphate), - 4,4'-(α-methylbenzylidene)bisphenol bis(diphenyl phosphate), - 1,1-bis-(4-hydroxyphenyl)cyclohexane)bis(diphenyl phosphate), - 9,9-bis(4-hydroxyphenyl)fluorene bis(diphenyl phosphate), - 1,1,1-tris(4-hydroxyphenyl)ethane tris(diphenyl phosphate), and Any mixture of them is selected from the group consisting of:

[0112] In one embodiment, the polyphosphorus compound in the oil used in accordance with the present invention is - hydroquinone bis(diphenyl phosphate) HDP, - 4,4'-dihydroxybiphenyl bis(diphenyl phosphate) and its oligomers, - 4,4'-dihydroxydiphenylthioether bis(diphenylphosphate), - 4,4'-dihydroxydiphenyl ether bis(diphenyl phosphate), - 1,3,5-phloroglucinol tris((diphenyl phosphate)), - 2-butyl 2-ethyl 1,3-propanediol bis(diphenyl phosphate), - Trimethylolpropane tris(diphenyl phosphate), - 2,2'-dihydroxybenzophenone bis(diphenyl phosphate), - 2,7-dihydroxynaphthalenebis(diphenylphosphate), - 4,4'-dihydroxybenzophenone bis(diphenyl phosphate), - bis(4-hydroxyphenyl)sulfonebis(diphenylphosphate), 4,4'-(hexafluoroisopropylidene)bis(diphenyl phosphate), - 4,4'-(α-methylbenzylidene)bisphenol bis(diphenyl phosphate), - 1,1-bis-(4-hydroxyphenyl)cyclohexane)bis(diphenyl phosphate), - 9,9-bis(4-hydroxyphenyl)fluorene bis(diphenyl phosphate), - 1,1,1-tris(4-hydroxyphenyl)ethane tris(diphenyl phosphate) - any mixture thereof is selected from the group consisting of:

[0113] In one embodiment, the polyphosphorus compound in the oil used in accordance with the present invention is - hydroquinone bis(diphenyl phosphate) HDP, - 4,4'-dihydroxybiphenyl bis(diphenyl phosphate) and its oligomers, - 4,4'-dihydroxydiphenylthioether bis(diphenylphosphate), - 4,4'-dihydroxydiphenyl ether bis(diphenyl phosphate), - 1,3,5-phloroglucinol tris(bis(diphenyl phosphate)), - 2-butyl 2-ethyl 1,3-propanediol bis(diphenyl phosphate), - Trimethylolpropane tris(diphenyl phosphate), 1,12-n-dodecanediol bis(diphenyl phosphate), - tetrakis(2,6-dimethylphenyl)-m-phenylene bisphosphate, - tetrakis(2,6-dimethylphenyl)-p-phenylene bisphosphate, and Any mixture of them is selected from the group consisting of:

[0114] In one embodiment, the polyphosphorus compound in the oil used in accordance with the present invention is - 4,4'-dihydroxydiphenylthioether bis(diphenylphosphate), - 4,4'-dihydroxydiphenyl ether bis(diphenyl phosphate), - 1,3,5-phloroglucinol tris(bis(diphenyl phosphate)), - 2-butyl 2-ethyl 1,3-propanediol bis(diphenyl phosphate), - Trimethylolpropane tris(diphenyl phosphate), 1,12-n-dodecanediol bis(diphenyl phosphate), - tetrakis(2,6-dimethylphenyl)-m-phenylene bisphosphate, - tetrakis(2,6-dimethylphenyl)-p-phenylene bisphosphate, and Any mixture of them is selected from the group consisting of:

[0115] The polyphosphorus compounds are present in the oils used in the present invention in amounts such as those conventionally used in the art, for example, they can be used in amounts of 0.1 to 10% by weight, preferably 0.5 to 5% by weight, based on the total weight of the oil.

[0116] Suitable oils for use in the present invention are described below.

[0117] The oils used in accordance with the present invention may contain all of the conventional components and additives known in the art for oils of this type.

[0118] The oils used in accordance with the present invention preferably comprise an ester base, at least one amine antioxidant, and at least one polyphosphorus antiwear additive of formula (I).

[0119] In some embodiments, the oil used according to the present invention also contains at least one additional additive. This at least one additional additive may be selected from the group consisting of lubricants, other anti-wear additives, antioxidants, metal corrosion inhibitors, passivators, viscosity index improvers, detergents or dispersants, antifoam agents, surfactants, foaming agents, tackifiers, stabilizers, extenders, hydrolysis stabilizers, additives suitable for extreme pressure, pigments, and other masking agents, among others. Such additives and agents are well known to those skilled in the art and are commercially available.

[0120] The ester base is a conventional ester base well known in the art, which is typically a synthetic oil that can be selected from monohydric or polyhydric alcohol esters, preferably polyhydric alcohol esters, with mono- or dicarboxylic acid reagents.

[0121] Particularly suitable polyhydric alcohols are neopolyols such as neopentyl glycol, 2-ethyl-2-methylpropane-1,3-diol, trimethylolethane, trimethylolpropane, trimethylolbutane and mono-, di- or tri-pentaerythritol.

[0122] Other suitable polyhydric alcohols include those of the formula R(OH)p wherein R is an optionally substituted linear, branched, or cyclic aliphatic hydrocarbon moiety, and p is an integer greater than or equal to 2. The polyhydric alcohol may be selected from the group consisting of 2-ethyl-1,3-hexanediol, 2-propyl-3,3-heptanediol, 2-butyl-1,3-butanediol, 2,4-dimethyl-1,3-butanediol, ethylene glycol, propylene glycol, and polyalkylene glycol.

[0123] Particularly suitable monohydric alcohols are neoalcohols such as 2,2,4-trimethylpentanol and 2,2-dimethylpropanol. Alternatively, the monohydric alcohol can be selected from the group consisting of methyl alcohol, butyl alcohol, isooctyl alcohol, and octadecyl alcohol.

[0124] The carboxylic acid reagent used to form the ester with the monohydric or polyhydric alcohol can be selected from optionally substituted aliphatic carboxylic acids containing one or two carboxylic acid functional groups or mixtures thereof. Those skilled in the art will know how to select the carboxylic acid to be used depending on the desired properties for the ester and on the monohydric or polyhydric alcohol used.

[0125] Ester base oils that may be used in accordance with the present invention include octyl acetate, decyl acetate, octadecyl acetate, methyl myristate, butyl stearate, methyl oleate monoesters, and dibutyl phthalate, dioctyl adipate, di-2-ethylhexyl azelate, and ethylhexyl sebacate polyesters. Polyol ester-type base oils can be oils prepared from technical pentaerythritol or trimethylolpropane and a mixture of carboxylic acids having 4 to 12 carbon atoms. Technical pentaerythritol is a mixture containing approximately 85% to 92% by weight of monopentaerythritol and 8% to 15% by weight of dipentaerythritol.

[0126] Conventional commercially available industrial pentaerythritol contains about 88% by weight of monopentaerythritol and about 12% by weight of dipentaerythritol, based on the total weight of the ester-type base oil. Industrial pentaerythritol may also contain amounts of tri- and tetra-pentaerythritol, which are normally formed as by-products during the production of industrial pentaerythritol.

[0127] Aromatic amine antioxidants are well known in the art and can be monomeric or polymeric aromatic amine antioxidants that belong to the family of aromatic amines and / or phenolic compounds.

[0128] The monomeric aromatic amine antioxidant may comprise, inter alia, at least one diphenylamine unsubstituted or substituted with at least one hydrocarbon group, at least one naphthylphenylamine unsubstituted or substituted with at least one hydrocarbon group, at least one phenothiazine unsubstituted or substituted with at least one hydrocarbon group, or any mixture thereof. The hydrocarbon group substituting the amine may be selected from the group consisting of (C1-C 30 ) alkyl group, or styrene.

[0129] Polymeric aromatic amine antioxidants are the polymerization products of aromatic amine antioxidants as defined above, either with each other or in the presence of different comonomers. Examples of oligomeric or polymeric aromatic amine antioxidants that can be used in turbine oils according to the invention include those described in French Patent No. 2 924 122 and WO 2009 / 071857.

[0130] The present invention therefore provides a method for producing an oil that is non-neurotoxic or has significantly reduced neurotoxicity (compared to tricresyl phosphate-based oils and their analogs or oils containing other neurotoxic phosphorus compounds), particularly for use in lubricating devices / machines, such as aircraft or aeroderivative turbines, comprising the steps of: incorporating into a base oil, such as an ester oil, at least one antiwear agent, wherein said at least one antiwear agent is represented by formula (I): [ka] (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from a linear alkylene group containing 7 to 36 carbon atoms or a branched alkylene group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; Each of X1 and X2 independently represents a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5. of, and in particular, has a risk level in terms of neurotoxicity of 0 The method may further comprise the step of: selecting from at least one polyphosphorus compound.

[0131] Of course, the various embodiments described above regarding the use of polyphosphorus compounds to prevent and / or reduce the neurotoxicity of oils also apply to this method of producing oils and will not be repeated below.

[0132] The present invention also relates to the use of at least one anti-wear additive in an oil, said at least one anti-wear additive being represented by formula (I) [ka] (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from an alkylene group containing 7 to 36 carbon atoms or a branched alkylene group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; Each of X1 and X2 independently represents a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5. The present invention relates to the use of a polyphosphorus compound of formula (I) for the prevention of aerotoxic syndrome, preferably in the case of a fume event.

[0133] Naturally, the various embodiments described above with respect to the use of polyphosphorus compounds to prevent and / or reduce the neurotoxicity of oils also apply to this use and will not be repeated below.

[0134] In the case of aeroderivative turbines, a condition referred to as "aerotoxic syndrome" is a condition that has at least some of the same neurological and reproductive symptoms as those observed in aircraft associated with aerotoxic syndrome, but that is contracted through exposure to organophosphates, such as tricresyl phosphate, during the erection of industrial land-based turbines, such as on offshore platforms.

[0135] The term "prevention of aerotoxic syndrome" refers to a reduction in the occurrence and / or intensity, or substantial or complete elimination, of at least one symptom identified as being associated with acute or chronic exposure of an individual to aircraft cabin air contaminated with oil, such as turbine oil or hydraulic oil, in gas and / or aerosol form. In some embodiments, prevention of aerotoxic syndrome refers to a reduction in the occurrence, or substantial or complete elimination, of some symptoms, preferably all symptoms, identified as being associated with acute or chronic exposure of an individual to aircraft cabin air contaminated with oil, such as turbine oil or hydraulic oil, in gas form, aerosol-type, airborne dispersed products.

[0136] In particular, the condition may be a neurological, neurobehavioral, neuromuscular and / or reproductive-related condition. Conditions whose occurrence and / or intensity may be reduced by use according to the invention include, for example, psychiatric or psychogenic disorders, chronic fatigue syndrome, severe migraines, multiple chemical sensitivity, mysterious viral infections, sleep disorders, depression, stress and anxiety.

[0137] The term "fume event" refers to the acute or chronic exposure, preferably acute exposure, of at least one individual to the air in an aircraft cabin contaminated with oil, such as turbine oil or hydraulic oil, in the form of gas and / or aerosol. A fume event can, in severe cases, be detected by the perception of, among other things, an unpleasant, characteristic odor, typically "dirty socks" or "wet dog." In the most severe cases, smoke or a thick white mist may be visible, for example, after a bearing failure in a turbine.

[0138] The present invention therefore provides a method of lubricating a machine / device, such as an aircraft or aeroderivative turbine, comprising the following steps: - providing a non-neurotoxic or significantly reduced toxic (risk level of 0 rating), preferably free of tricresyl phosphate and / or its analogues, oil, said oil comprising a compound of formula (I) [ka] (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from a linear alkylene group containing 7 to 36 carbon atoms or a branched alkylene group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; Each of X1 and X2 independently represents a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5. and adding at least one antiwear agent selected from the group consisting of polyphosphorus compounds of the formula: - applying an effective amount of said oil to said machine / device. The present invention relates to a method comprising:

[0139] Of course, the various embodiments described above regarding the use of polyphosphorus compounds to prevent and / or reduce the neurotoxicity of oils also apply to this method of lubrication and will not be repeated below. [Example]

[0140] Example 1: Toxicity studies and especially neurotoxicity studies The polyphosphorus compounds of the present invention were studied in terms of cholinesterase inhibition, 3D molecular modeling with spherical harmonics, and QSAR modeling for neurotoxicity and reproductive toxicity, and compared with other phosphorus compounds, including TCP. Correlations between the results obtained allowed the determination of a "safety level" for the use of these compounds as antiwear additives in aircraft or aeroderivative turbine oils.

[0141] Protocols for the different tests performed Measurement of inhibitory concentrations for two cholinesterases To the extent that the toxic activity of TCP is particularly related to its action on cholinesterases, the effects of the compounds used according to the invention, as well as comparative compounds, on the two cholinesterases were studied. The concentration values ​​of each compound required to inhibit 50% of the activity of the two cholinesterases were determined. The 50% inhibitory concentration (IC 50 ) the higher the compound is, the less neurotoxic it has, as it has a weaker effect on cholinesterase.

[0142] The inhibitory potential of compounds on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) biological activity was assessed using the spectroscopic method of Ellman (Ellman et al., Biochem. Pharm. 1961, 7, 88-95).

[0143] Acetylthiocholine and butyrylthiocholine iodides, and 5,5-dithiobis(2-nitrobenzoic) acid (DTNB) were purchased from Sigma Aldrich (Steinheim, Germany).

[0144] BuChE lyophilized from horse serum (eqBuChE, Sigma-Aldrich) was dissolved in 0.1 M phosphate buffer (pH 7.4) to obtain an enzyme stock solution with an enzymatic activity of 2.5 units / mL. Human erythrocyte AChE (hAChE, aqueous buffer, ≥500 units / mg protein (BCA), Sigma-Aldrich) was diluted in 20 mM HEPES buffer, pH 8, containing 0.1% Triton X-100 to obtain an enzyme solution with an enzymatic activity of 0.25 units / mL.

[0145] In this procedure, 100 μL of 0.3 mM DTNB dissolved in phosphate buffer, pH 7.4, was added to a 96-well plate, followed by 50 μL of a 50 μL solution of the test compound and 50 μL of enzyme (final 0.05 U). After a 5-minute pre-incubation at 25°C, the reaction was initiated by injecting 50 μL of a 0.1 mM acetyl iodide or butyrylthiocholine solution. The hydrolysis of acetyl or butyrylthiocholine was followed at a wavelength of 412 nm using a microplate reader (Synergy 2, Biotek, Colmar, France) by the formation of yellow 5-thio-2-nitrobenzoate anion as the product of the reaction between DTNB and the thiocholine released by the enzymatic hydrolysis of acetyl or butyrylthiocholine. The compounds to be tested were dissolved in analytical-grade DMSO at 5 × 10 s. -3 The compounds were dissolved in 100 mL of acetyl iodide solution to a concentration of 100 M. Donepezil or tacrine were used as reference standards. The rate of increase in absorbance at 412 nm was measured 4 minutes after addition of the acetyl iodide or butyrylthiocholine solution. Tests were performed with blanks containing all of the compounds except for acetyl or butyrylthiocholine to take into account non-enzymatic reactions.

[0146] The percentage of inhibition due to the presence of the test compound is calculated by the formula: ((v0-vi) / v0)×100 (In the formula, v i is the rate calculated in the presence of inhibitor, and v0 is the enzyme activity) was calculated using

[0147] I C50 Values ​​were determined graphically by plotting the percentage of inhibition as a function of the logarithm of the six inhibitor concentrations in the test solution using GraphPad Prism software (version 6.01, GraphPad Software, La Jolla, Calif., USA). All experiments were performed in triplicate.

[0148] Molecular modeling with spherical harmonics The 3D modeling method used in the present invention is described in the publication: "Benchmarking of HPCC: A novel 3D molecular representation combining shape and pharmacophoric descriptors for efficient molecular similarity assessments", Karaboga et al. 2013 Journal of Molecular Graphics and Modelling 41;20-30.

[0149] Two clusters (clusters 1 and 2) were defined by their similarity to monophosphate compounds known to be neurotoxic and reproductive toxins, including, inter alia, tri(ortho-cresyl)phosphate ToCP, tri(meta-cresyl)phosphate, tri(para-cresyl)phosphate, trixylyl phosphate, and saligenin cresyl phosphate.

[0150] A third cluster of possibly toxic compounds was identified (cluster 5), including reproductively toxic, mutagenic, and carcinogenic RMC compounds, particularly tri(n-butyl phosphate).

[0151] Studies of the polyphosphorus compounds used according to the invention have shown that they belong to a different cluster (cluster 3) associated with non-toxic molecules according to the characterization studies described so far.

[0152] QSAR modeling The neurotoxicity and reproductive toxicity of various compounds used in accordance with the present invention and other monophosphate compounds was evaluated by QSAR (Quantitative Structure Activity Relationship) modeling.

[0153] Selection of training and validation sets The training set was defined by chemical structures collected from several publicly available sources: HSBD (Hazardous Substances Data Bank), EPA (US Environmental Protection Agency), ECHA (European Chemicals Agency), and NTP (National Toxicology Program). 247 compounds were classified as neurotoxic, 2214 compounds as reproductively toxic, and 1697 compounds were classified as neither neurotoxic nor reproductively toxic, forming the non-toxic training set.

[0154] The validation set was constructed using compounds from a different dataset than that used for the training set. Molecules already found in the training set were removed. The validation set consisted of 70 compounds classified as neurotoxic compounds, 506 compounds classified as reproductively toxic compounds, and 256 compounds classified as neither neurotoxic nor reproductively toxic, forming a non-toxic validation set.

[0155] QSAR model performance A generalized linear model (GLM) was selected to perform a quantitative structure / activity relationship (QSAR) approach. GLM models were separately trained to distinguish chemical structures into (i) neurotoxic and non-neurotoxic compounds and (ii) reproductive toxic and non-reproductive toxic compounds. This approach resulted in a GLM model with 210 significant descriptors in the training set. During training, the performance of the QSAR model was measured by receiver operator characteristic (ROC) curves, which yielded Area Under Curve (AUC) values ​​of 0.90 or greater for predicting neurotoxicity and reproductive toxicity, respectively.

[0156] To validate the robustness of the QSAR models, they were then used to predict (i) the neurotoxicity category (i.e., neurotoxic / non-neurotoxic categorization) of the compounds in the validation set, and (ii) the reproductive toxicity category (i.e., reproductive / non-reproductive categorization) of the compounds in the validation set. During validation, the performance of the QSAR models was measured by the area under the curve (AUC) value, and critical values ​​of 0.70 or greater were obtained for predicting neurotoxicity and reproductive toxicity, respectively.

[0157] The polyphosphorus compounds according to the present invention were then studied using a GLM-based QSAR model.

[0158] Synthesis of polyphosphorus compounds according to the present invention In a four-neck flask equipped with a stirrer, coolant, separatory funnel, thermowell, and nitrogen bubbler, 1 molar equivalent of reagent A (dialcohol, diamine, or aminoalcohol) and 3.35 molar equivalents of triethylamine are introduced. The reaction medium is diluted with approximately 10 volumes of toluene relative to reagent A. Depending on the nature of reagent A, the reaction medium is heated between 25 and 110 °C, and then 2.2 molar equivalents of phosphate chloride are added dropwise using a separatory funnel. At the end of the reaction, the formed triethylamine salt is removed by filtration and then washed with 5 volumes of ethyl acetate. The filtrate is then washed twice with 0.1 N HCl solution, twice with 0.1 N KOH solution, and then with water until neutral pH is reached. The organic layer is then dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting crude reaction product is purified by silica gel chromatography, liquid-liquid extraction, or precipitation. The product thus obtained is analyzed by GC (gas chromatography) or GPC (gel permeation chromatography) chromatography. 1 H and / or 31 Characterization is performed by P-NMR analysis. The yields obtained range from 15 to 75%.

[0159] result The results of the tests carried out are shown in Figures 2 to 9. The penultimate column corresponds to a risk level rating regarding the safety of these molecules for use in oils such as turbine oils and their alleged cabin toxicity. A rating of 5 corresponds to a very high risk in terms of neurotoxicity and / or reproductive toxicity, while a rating of 0 or 1 corresponds to a very low or zero risk level. The risk levels are determined based on the in vivo experimental results of inhibition (hAChE IC 50 and eqBuChE IC 50The risk score is determined by the sum of factors corresponding to each independently assessed risk based on the following thresholds: IC for hAChE, semi-empirical predictions (neurotoxicity QSAR model and reproductive toxicity QSAR model), and molecular modeling (clustering) with spherical harmonics, which can range from 0 to 5. A value of 0 indicates absence of risk, and a value of 5 indicates very high multiple risk. For each risk, a factor of 0 or 1 is assigned depending on whether the value is above or below the threshold: IC for hAChE 50 15 mg / L for eqBuChE, IC 50 15 mg / L for toxicity, 0.2% for neurotoxicity, and 3% for reproductive toxicity.

[0160] The compounds are numbered as follows: Comparative Example: Compound A: 2-ethylhexyl diphenyl phosphate (CAS 1241-94-7) (https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.013.625) Compound B: Tri(ortho-cresyl)phosphate ToCP Compound C: Tri(meta-cresyl)phosphate Compound D: Tri(para-cresyl)phosphate Compound P: Tricresyl phosphate (CAS 1330-78-5) corresponds to the commercial product Durad 125 (https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.239.100) Compound E: Trixylyl phosphate (CAS 25155-23-1) (https: / / echa.europa.eu / fr / registration-dossier / - / registered-dossier / 2204 / 7 / 11 / 1) Compound F: Tri(2,6-difluorophenyl)phosphate Compound G: Tri(4-isopropylbenzoate)phosphate Compound H: Di(p-tertbutylphenyl)phenyl phosphate Compound I1: Triphenyl phosphate (CAS 204-112-2) (https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.013.625) Compound I2: Tri(p-tert-butylphenyl)phosphate Compound I3: Tert-butylphenyl diphenyl phosphate (CAS 700-990-0) corresponds to the commercial product Durad 150B (https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.235.046) Compound J: Saligenin cresyl phosphate Compound K: Diphenyl phosphoramidate Compound L: Tris(2-ethylhexyl)phosphate (CAS 78-42-2) (https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.001.015) Compound M: Tri(n-butyl phosphate) (CAS 126-73-8) https: / / echa.europa.eu / fr / registration-dossier / - / registered-dossier / 13548 Compound N: Tris(chloroethyl)phosphate (CAS 115-96-8) https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.003.744 Compound Q: Tri(isobutyl)phosphate (CAS 126-71-6) (https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.004.363) Compound R: Dibutyl [[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]succinate (CAS 68413-48-9) (https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.063.817) Compound S: 2,6-pyridinediol bis(diphenyl phosphate) Compound T: Neopentyl glycol bis(diphenyl phosphate) Compound U: 1,6'-n-hexanediol bis(diphenyl phosphate) Compound V: 1,4'-n-butanediol bis(diphenyl phosphate) Compound W: Tetrakis(2-chloroethyl)dichloroisopentyl diphosphate (CAS 38051-10-4) https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.048.856 (Compound V6 from the publication by Ike van der Veen) Compounds of the invention: Compound 1: Hydroquinone bis(diphenyl phosphate) HDP Compound 2: 4,4'-dihydroxybiphenylbis(diphenylphosphate) BDP and its oligomers https: / / echa.europa.eu / fr / substance-information / - / substanceinfo / 100.225.031 Compound 3: 4,4'-dihydroxydiphenylthioether bis(diphenylphosphate) Compound 4: 4,4'-dihydroxydiphenyl ether bis(diphenyl phosphate) Compound 5: 1,3,5-phloroglucinol tris(bis(diphenyl phosphate)) Compound 6: 2-butyl-2-ethyl-1,3-propanediol bis(diphenyl phosphate) Compound 7: Trimethylolpropane tris(diphenyl phosphate) Compound 8: Tetrakis(2,6-dimethylphenyl)-m-phenylene bisphosphate https: / / echa.europa.eu / en / substance-information / - / substanceinfo / 100.103.102 Compound 9: Tetrakis(2,6-dimethylphenyl)-p-phenylene bisphosphate Compound 10: 1,12-n-dodecanediol bis(diphenyl phosphate)

[0161] Compounds of the triarylphosphate type (TCP family) belong overall to cluster 1 with risk levels varying from 2 to 5 with an average of 3.6 for the 8 fully characterized molecules.

[0162] Compounds 1 to 10 having formula (I) according to the present invention have high IC 50 It exhibits a value of 0.001 and belongs to the cluster of non-toxic molecules (cluster 3), with low neurotoxicity and low reproductive toxicity, and therefore a level of risk equal to 0.

[0163] Without being bound by any theory, the structure of the compounds of formula (I) allows them to achieve a particular three-dimensional structure that is different from that of toxic compounds such as TCP, and that confers on them non-toxic properties.

[0164] The compounds in Cluster 1, according to a spherical harmonic 3D modeling approach, have a "three-bladed propeller" morphology based on two planes meeting at right angles at the center or core of the molecule, while the compounds in Cluster 3 exhibit a rather extended, flattened shape resembling a butterfly morphology. The molecules resulting from the spherical harmonic modeling work are shown in Figure 1. These compounds are therefore non-neurotoxic and non-reproductively toxic alternatives to tricresyl phosphate and its triaryl phosphate analogues.

[0165] In comparison, compound I2, described in WO 2010 / 149690, has reduced inhibition of butyrylcholinesterase but is found to be active against acetylcholinesterase. Modeling classifies the latter as part of cluster 1, which confirms the experimental results with acetylcholinesterase.

[0166] Thus, in vitro tests and modeling tests (spherical 3D or QSAR) show that the applicant has non-arbitrarily selected a limited subset of compounds of general formula (I) from all existing phosphorus-based compounds that generally exhibit antiwear activity in oils. This subset also has a technical effect different from other phosphorus-based compounds. Indeed, this subset of polyphosphorus compounds of formula (I) is at least non-neurotoxic and is capable of and / or configured to reduce and / or prevent neurotoxicity of oils, particularly turbine oils for aviation. Furthermore, this subset allows and / or is configured for the prevention of aerotoxic syndrome, particularly in the event of a fume event. Thanks to its properties, this subset allows for the formulation of turbine oils, for example for aviation, that are suitable and / or configured to enable an increased level of safety in aviation and other aeroderivative applications.

[0167] Additionally, no indication in the prior art could enable a person skilled in the art to specifically select this subset of compounds of general formula (I) for reducing / preventing the neurotoxicity of turbine oils or for the prevention of aerotoxic syndrome.

[0168] Indeed, on the other hand, other polyphosphorus compounds, and in particular other polyphosphorus compounds used as antiwear agents in oils and known in the prior art, do not have this novel technical effect (i.e.: reducing and / or preventing the neurotoxicity of oils or preventing aerotoxic syndrome).On the contrary, other antiwear compounds and other organophosphorus compounds known and used in the field of aviation lubricants and oils (e.g. compounds E, P, I1-3, L, R and M, the latter used in aviation hydraulic oils) are neurotoxic.

[0169] On the other hand, prior to the tests carried out by the applicant, most of the other commercially available and registered phosphorus compounds, especially known as anti-wear agents, such as compounds A, P, I1, I3, Q and R, have been recognized, in particular by the official website of the European Chemical Agency (ECHA), as not presenting a significant risk of acute or severe toxicity (CMR characteristics). ECHA is the competent authority that decides on the toxicity of registered chemicals for the European market. It publishes public data and generally accepted scientific data. Compound I3 is particularly used in the field of lubricants to replace TCP or its analogues. However, IC 50 The applicant's tests, both in vivo and by 3D or QSAR modeling, show, to the contrary, that these compounds are highly neurotoxic. For example, according to the ECHA website, compound I3 is not known to be toxic to human health. The table in Figure 5 now shows that this compound I3 is a mixture of neurotoxic compounds belonging to cluster 1, including triphenyl phosphate and tri(p-tert-butylphenyl) phosphate. The same applies to compound A, which, according to the ECHA website, shows no signs of neurotoxicity but has a risk level of 4. A person skilled in the art would therefore not have been guided or prompted (especially from known and publicly available data) to select the subset formed by compounds of general formula (I) in order to reduce and / or prevent the neurotoxicity of oils or to prevent aerotoxicity syndrome.

[0170] IC for cholinesterases hAChE and eqBuChE 50 The inhibitory values ​​were also tested for other comparative compounds and for the compound according to the invention. This complementary study confirms the very high safety level of the compound of formula (I). Table 1 below shows the experimental results obtained.

[0171] [Table 1]

[0172] [Table 2]

[0173] [Table 3]

[0174] [Table 4]

[0175] Among a new series of 16 compounds bearing at least two phosphate functional groups, the vast majority (13 / 16, i.e., over 80%) have low inhibition levels, IC50, of above 15 mg / L against the two cholinesterases. Unexplainably / surprisingly, compounds bearing groups or atoms that qualify as electron-withdrawing due to inductive or conjugation effects, such as chlorine, carbonyl, or nitrogen atoms in the aromatic ring, exhibit lower associated safety levels. The spacing of the phosphate functional groups also appears to be important for the inhibitory outcome, with functional groups located in the meta (i.e., 1,3) position on the aromatic ring appearing to result in less favorable geometries than those located in the para (i.e., 1,4) or more distal positions (in the case of 2,7-naphthalene derivatives).

[0176] Example 2: Anti-wear performance of polyphosphorus compounds used according to the present invention The antiwear performance of the turbine oils used in accordance with the present invention was measured using a four-ball wear test in accordance with standard ASTM D4172 test method, and the results obtained are shown in Table 2 below.

[0177] [Table 5]

[0178] These results confirm that the polyphosphorus compounds used in accordance with the present invention in oils have interesting and potentially similar antiwear properties to those of TCP, and therefore are suitable for effective use in oils, particularly oils for aircraft or aeroderivative turbines.

[0179] Of course, various other modifications can be made within the scope of the appended claims.

Claims

1. 1. The use of at least one anti-wear additive in an oil, wherein said at least one anti-wear additive is a compound represented by formula (I): 【Chemistry 1】 (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from an alkylene group containing 7 to 36 carbon atoms or a branched alkylene group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; X １ , and X ２ are independently a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5. for reducing and / or preventing neurotoxicity of said oil, preferably turbine oil.

2. 1. The use of at least one anti-wear additive in an oil, wherein said at least one anti-wear additive is a compound represented by formula (I): 【Chemistry 2】 (In the formula, each of R1, R2, R3, and R4 is independently selected from an alkyl, O-alkyl, aryl, or O-aryl group; A is a divalent group selected from an alkyl group containing 7 to 36 carbon atoms or a branched alkyl group containing 6 to 36 carbon atoms, a monocyclic, polycyclic, or polyaromatic arylene group, or an aralkylene group; X １ , and X ２ are independently a single bond, an oxygen atom, or a nitrogen atom; n is an integer ranging from 1 to 5.

10. Use comprising at least one polyphosphorus compound of formula (I) above, preferably in the case of a fume event, for the prevention of aerotoxic syndrome.

3. 3. Use according to claim 1 or 2, wherein the oil and / or the at least anti-wear additive does not contain tricresyl phosphate or any additive other than the polyphosphorus compound of formula (I).

4. When A is a monocyclic arylene group, X １ and X ２ are on opposite sides, in particular in the 1,4-positions, when the monocyclic arylene group contains 6 carbon atoms; preferably, when A is phenylene, X1 and X2 are not in the ortho or meta positions, unless at least one, preferably all, of the groups R1, R2, R3 and R4 is an O-phenyl group substituted with two methyl groups, in particular in the 2,6-positions, or the phenylene is substituted with O-diphenylphosphate.

5. When A is a polycyclic arylene group or a polycyclic aromatic arylene group, X １ and X ２ are located on opposite sides, preferably when A is naphthalene, X1 and X2 are located on opposite sides, typically when A is naphthalene, X1 and X2 are not in the ortho or meta positions.

6. The use according to any one of claims 1 to 5, wherein the oil is selected from the group consisting of aircraft or aeroderivative turbine oils, helicopter transmission oils and weapons fluids.

7. The use according to any one of claims 1 to 6, wherein R1, R2, R3 and R4 are O-phenyl or O-dimethylphenyl groups, such as O-2,6-dimethylphenyl.

8. A is 1,4-phenyl, 4,4'-biphenyl, 4,4'-diphenylthioether, 4,4'-diphenylether, 1,3-(5 O-[(diphenyl)phosphate)]phenyl, 1,3-(2-ethyl-2-butyl)propyl, 1,3-(2-ethyl-2-[methyl-O-diphenylphosphate])propyl, 4,4'-[diphenyl(dimethyl)-methylidene], 2,2'-benzophenone, 2,7-naphthalene, 1,2-ethyl, 4,4'-[diphenylphenylethylidene], 4,4'-diphenylsulfone, 4,4'-diphenyl-hexafluoropropane, 1,4-[(2-phenyl) 8. The use according to any one of claims 1 to 7, wherein the alkyl group is selected from the group consisting of 1,4-[(2,5-di-tert-butyl)phenyl], 1,4-[(2-chloro)phenyl], 4,4'-benzophenone, 1-hydroxy-3-thiophenyl, 1,6-hexyl, 1,4-naphthalene, 2,6-anthracene, 9,10-anthracene, 1,10-decyl, 1,12-n-dodecyl, 2,5-dimethyl-2,5-hexyl, 1,12-dodecyl and 1,3-naphthalene groups.

9. 8. The use according to any one of claims 1 to 7, wherein A is an optionally substituted alkylene group, a substituted monocyclic arylene group or a polycyclic arylene group, wherein at least two rings are linked by at least a covalent bond between two different atoms belonging to each of said rings, and wherein said covalent bond between said two rings is interrupted by at least one heteroatom or heteroatom group.

10. The polyphosphorus compound is - hydroquinone bis(diphenyl phosphate) HDP, 4,4'-dihydroxybiphenylbis(diphenylphosphate) and its oligomers, 4,4'-dihydroxydiphenylthioether bis(diphenylphosphate), 4,4'-dihydroxydiphenyl ether bis(diphenyl phosphate), 1,3,5-phloroglucinol tris((diphenyl phosphate)), 2-butyl 2-ethyl 1,3-propanediol bis(diphenyl phosphate), - trimethylolpropane tris(diphenyl phosphate), 4,4'-dihydroxydiphenylphenylethylidenebis(diphenylphosphate), 4,4'-dihydroxydiphenylsulfone bis(diphenylphosphate), 4,4'-dihydroxybenzophenone bis(diphenyl phosphate), 2,2'-dihydroxybenzophenone bis(diphenyl phosphate), 4,4'-dihydroxydiphenylhexafluoropropane bis(diphenyl phosphate), 1,4-dihydroxynaphthalenebis(diphenylphosphate), 1,3-dihydroxynaphthalenebis(diphenylphosphate), 2,7-dihydroxynaphthalenebis(diphenylphosphate), - ethanolamine diphenyl phosphate diphenyl phosphoramidate, 4,4'-diaminodiphenyl ether bis(diphenyl phosphoramidate), 2,6-dihydroxyanthracenebis(diphenyl phosphate), 9,10-dihydroxyanthracenebis(diphenyl phosphate), 1,4-dihydroxy[(2-phenyl)phenyl]bis(diphenyl phosphate), 1,4-dihydroxy[(2,5-diterbutyl)phenyl]bis(diphenyl phosphate), 1,4-dihydroxy[(2-chloro)phenyl]bis(diphenyl phosphate), 1,3-dihydroxythiophene bis(diphenyl phosphate), 1,6-hexanediol bis(bis(diphenyl phosphate), 1,10-decanediol bis(diphenyl phosphate), 2,5-dimethyl 2,5-hexanediol bis(diphenyl phosphate), 1,12-n-dodecanediol bis(diphenyl phosphate), tetrakis(2,6-dimethylphenyl)-m-phenylene bisphosphate, tetrakis(2,6-dimethylphenyl)-p-phenylene bisphosphate, - phenylhydroquinone bis(diphenyl phosphate) DPP, tert-butylhydroquinone bis(diphenyl phosphate), 2,5-di-tert-butylhydroquinone bis(diphenyl phosphate), 1,4-dihydroxynaphthalenebis(diphenylphosphate), 2,7-dihydroxynaphthalenebis(diphenylphosphate), 4,4'-dihydroxybenzophenone bis(diphenyl phosphate), bis(4-hydroxyphenyl)sulfonebis(diphenylphosphate), 4,4'-(hexafluoroisopropylidene)bis(diphenyl phosphate), 4,4'-(α-methylbenzylidene)bisphenol bis(diphenyl phosphate), 1,1-bis-(4-hydroxyphenyl)cyclohexane)bis(diphenyl phosphate), 9,9-bis(4-hydroxyphenyl)fluorene bis(diphenyl phosphate), 1,1,1-tris(4-hydroxyphenyl)ethane tris(diphenyl phosphate), and Any mixture of them The use according to any one of claims 1 to 8 and 9 (in part) selected from the group consisting of:

11. The use according to any one of claims 1 to 10, wherein the oil further comprises an ester base and at least one amine antioxidant.

12. 12. Use according to any one of claims 1 to 11, wherein the at least polyphosphorus compound is present in the oil in an amount of 0.1 to 10% by weight, preferably 0.5 to 5% by weight, based on the total weight of the oil.

13. IC ５０ The 50% inhibitory concentration of the at least one compound of formula (I) on the biological activity of the acetylcholinesterase (AChE) enzyme, referred to as hAChE, is 15 mg / L or more, and the IC ５０ Use according to any one of claims 1 to 12, wherein the 50% inhibitory concentration for the activity of the butyrylcholinesterase enzyme, called eqBuChE, is 50 mg / L or more, preferably 55 mg / L or more, in particular 60 mg / L or more, typically 70 mg / L or more.

14. 14. The use according to any one of claims 1 to 13, wherein the compound of formula (I) belongs to cluster 3 as determined according to molecular modeling by the spherical harmonics method as described in the publication "Benchmarking of HPCC: A novel 3D molecular representation combining shape and pharmacophoric descriptors for efficient molecular similarity assessments", Karaboga et al. 2013 Journal of Molecular Graphics and Modelling 41; 20-30.

15. The compounds of formula (I) were identified by quantitative structure-activity relationship (QSAR) modeling. - 0.70% or less, preferably 0.50% or less, typically 0.15% or less for the measurement of neurotoxicity, termed Neurotoxicity QSAR; - 1.5% or less, preferably 1.15% or less, typically 0.55% or less for the determination of reproductive toxicity, termed the Reproductive Toxicity QSAR The use according to any one of claims 1 to 14, wherein the percentage value (%) is:

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