Process for the preparation of trifluoroethenylamines

Abstract

This invention relates to a method for preparing trifluoroethyleneamine (II) by reacting a molecule (I) with an amine compound in one or two steps: said method involves reacting a compound of formula (I) with a compound of formula (V): or with a compound of formula (III); to form a compound of formula (IV), which reacts with a compound of formula (V), wherein groups R1 and R2 together form a heterocycle or independently represent functional groups selected from hydrogen and aliphatic chains selected from C. 1‑12 Alkyl, C 1‑12 Heteroalkyl, C 6‑10 Aryl and C 4‑10 Heteroaryl groups, which optionally contain one or more substituents selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-, wherein X is a halogen.

Description

[0001] This invention relates to the chemistry of fluorinated organic compounds, and more specifically to the recycling of small polyfluorinated carbon molecules, typically containing fewer than three or even fewer than two carbon atoms, for the synthesis of larger compounds. Background Technology

[0002] Trifluoromethane, with the formula CHF3, is a byproduct of the polymer industry and is produced on a large scale, which is particularly harmful to the environment. Furthermore, its thermal decomposition requires excessive energy, contradicting the principles of sustainable development. There is a growing need to recycle this fluorocarbon compound, or its difluorinated analogues CHF2Br and CHF2I, which are currently considered primarily industrial waste, with the aim of converting them into products usable in the pharmaceutical, cosmetic, and agrochemical industries.

[0003] Fluorinated compounds account for 20% of all pharmaceuticals on the market and over 40% of all agrochemicals recently introduced to the market. Many of these compounds, particularly those containing -CF2- and CF3- groups, are currently prepared from simpler fluorinated structural units containing two or more carbon atoms. For example, major difluorinated C2 structural units include: ethyl difluoroethylene, which is prepared from tetrafluoroethylene (TFE); and ethyl bromodifluoroethylene, which is ultimately derived from restricted C2 halogenated fluorocarbon compounds such as 1,1,2-trichloro-1,2,2-trifluoroethane.

[0004] The industrial production of TFE and related (halogenated) fluorocarbons depends on the dimerization of CHF2Cl, the synthesis of which is accompanied by the formation of trifluoromethane (CHF3, HFC-23), a byproduct with extremely high global warming potential.

[0005] Given the environmental concerns associated with CHF3, recycling it into synthetically usable C2 fluorinated structural units appears to be a promising approach, as this makes the fluorinated chemicals value chain more efficient by directly utilizing CHF3 and reducing the need for polyhalogenated C2 derivatives, which are associated with additional CHF3 loads (in the case of TFE) and / or the potential for ozone depletion (in the case of halogenated fluorocarbons).

[0006] The following are known examples of directly converting CHF3 into fine chemical products (see Figure 1): - Transient formation and nucleophilic addition of CF3- anions (Figure 1a) (see Saito, T. et al., “Direct Nucleophilic Trifluoromethylation of Carbonyl Compounds by Potent Greenhouse Gas, Fluoroform”: Improving the Reactivity of Anionoid Trifluoromethyl Species in Glymes”, Scientific Reports, Vol. 8, No. 1, July 2018, p. 11501). Direct copperization of CHF3 yields a potent trifluoromethylating agent [CuCF3] (Figure 1b) (see the publication "Direct Cupration of Fluoroform" by Zanardi, A., Novikov, MA, Martin, E., Benet-Buchholz, J., and Grushin, VV). J . Am. Chem. Soc. 133, 20901–20913(2011)); - Synthesis of widely used TMSCF3 reagent (Figure 1c) (see publications by Prakash, GKS, Jog, PV, Batamack, PTD, and Olah, GA, entitled "Taming of Fluoroform: Direct Nucleophilic Trifluoromethylation of Si, B, S, and C Centers") Science 338, 1324–1327 (2012)]; - Difluoromethylation of nucleophilic anions at C / O or S sites mediated by difluorocarbene (Figure 1d) (see M. Köckinger et al., “Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as a Source of Difluoromethyl”, published in the journal). Org. Process Res. Dev. 22, 1553–1563 (2018)); - Synthesis of the CF3SO3H reagent (see publications by Mukhopadhyay, S., Bell, AT, Srinivas, RV, and Smith, GS: entitled "Synthesis of Trifluoromethanesulfonic Acid from CHF3", published in...) Org.Process Res.Dev. 8, 660–662 (2004)); - Synthesis of CF3Br reagent (see the publication by Skapin T. et al. entitled "Synthesis of Halogenated Methanes", published in...) Journal of Fluorine Chemistry Volume 45, Issue 1, October 1989, page 163.

[0007] Chart 1

[0008] Furthermore, Doklady Akademii Nauk SSSR's publication, Volume 161, Issue 6, pp. 1362-1364, describes the synthesis of N-fluorovinyl derivatives, which involves reacting lithium amide or potassium amide, substituted at the 1-position with an alkyl or aryl-1 group derived from diethylamine, piperidine, morpholine, methylaniline, and carbazole, with fluoroolefins such as tetrafluoroethylene, trifluorochloroethylene, trifluoroethylene, vinylidene fluoride, and hexafluoropropylene in solvents such as ether, tetrahydrofuran, or dioxane.

[0009] The chemical abstract titled “Reaction of direct fluoroalkenylation.I. Synthesis of trifluorovinyl and chlorodifluorovinylamines” (accession number: 1966:490544HCAPLUS full text) describes the reaction of perfluorovinyl groups with lithium amides corresponding to the amine groups of the final products.

[0010] Document JP S63 22546 A describes the decarboxylation of aminofluoropropionic acid, which yields the following compound: Me2N-CF=CF2.

[0011] None of these studies used compounds selected from CHF3 and CHF2Cl as starting reagents.

[0012] Technical issues This invention aims to provide a novel method for recovering compounds of the form CHF3, more generally CHF2X, where X is a halogen. Unlike the prior art methods using CHF3 shown in Figure 1, the method according to this invention aims to obtain a more versatile C2 reagent (typically trifluoroethyleneamine (TFVA)) that can be used as a synthon for the synthesis of known or novel fluorinated chemicals.

[0013] definition Within the scope of this invention, the described compounds may be substituted with any number of substituents or functional groups. Generally, the term "substituted," whether or not preceded by the term "optional," and the substituents contained in the formula of this invention, refers to the substitution of a hydrogen group in a given structure by a group of a specified substituent. When more than one position in a given structure may be substituted by more than one substituent selected from the specified group, the substituents may be the same or different at each position. In this document, the term "substituted" covers all permissible substituents in organic compounds. Generally, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic carbon and heteroatom substituents in organic compounds. For the purposes of this invention, heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents in the organic compounds described herein, satisfying the valence of the heteroatom. Furthermore, this invention is not intended to be limited in any way to permissible substituents in organic compounds. The combinations of substituents and variables contemplated in this invention are preferably those combinations that result in the formation of stable compounds that can be used to treat and prevent disorders or for specific purposes. Examples of substituents include, but are not limited to, the following: aliphatic; heteroaliphatic; alicyclic; heteroalicyclic; aromatic; heteroaromatic; aryl; heteroaryl; alkylaryl; alkylheteroaryl; alkoxy; aryloxy; heteroalkoxy; heteroaryloxy; alkylthio; arylthio; heteroalkoxy; heteroarylthio; F; Cl; Br; I; -NO2; -CN; -CF3; -CH2CF3; -CHCl2; -CH2OH; -CH2CH2OH; -CH2NH2; -CH2SO2CH3 and / or -GRG1, wherein G is -O-, -S-, -NRG2-, -C(=O)-, -S(=O)-, -SO2-, -C(=O)O-, -C(=O)NRG2-, -OC(=O)-, -NRG2C(=O)-, -OC( =O)O-, -OC(=O)NRG2-, -NRG2C(=O)O-, -NRG2C(=O)NRG2-, -C(=S)-, -C(=S)S-, -SC(=S)-, -SC(=S)S-, -C(=NRG2)-, -C(=NRG2)O-, -C(=NRG2)NRG3-, -OC(=NRG2)-, -NRG2C(=NRG3)-, -NRG2SO2-, -NRG2SO2NRG3- or -SO2NRG2-, wherein each occurrence of RG1, RG2 and RG3 independently includes, but is not limited to, hydrogen, halogen or optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aromatic, heteroaromatic, aryl, heteroaryl, alkylaryl or alkylheteroaryl groups. Other examples of commonly applicable substituents are shown by specific embodiments illustrated in the examples described later in the specification.

[0014] As used herein, the term "stable" preferably refers to a compound that has sufficient stability to allow its manufacture and to maintain its integrity for a period of time sufficient to be detected and preferably for the purposes described herein. The term "stability" may also refer to the ability to resist degradation, persist in a given environment, and / or maintain a particular structure.

[0015] As used herein, the term "aliphatic" includes saturated and unsaturated aliphatic hydrocarbons, whether straight-chain (i.e., unbranched) or branched, optionally substituted with one or more functional groups. As will be understood by those skilled in the art, the term "aliphatic" herein includes, but is not limited to, alkyl, alkenyl, and alkynyl groups. Thus, as used herein, the term "alkyl" includes both straight-chain and branched alkyl groups. Similar convention applies to other general terms such as "alkenyl," "alkynyl," etc. Additionally, herein, the terms "alkyl," "alkenyl," "alkynyl," etc., encompass both substituted and unsubstituted groups.

[0016] The term "alkyl" also includes the term "cycloalkyl". As used herein, the term "cycloalkyl" refers to, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc., which may optionally be substituted in the case of aliphatic, heteroaliphatic, or heterocyclic groups. Similar conventions apply to other general terms such as "cycloalkenyl", "cycloynyl", etc.

[0017] Examples of aliphatic groups in straight-chain and branched alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, allyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, tert-pentyl, n-hexyl, sec-hexyl, and other groups, which may also have one or more substituents. Alkenyl groups include, but are not limited to, vinyl, propenyl, butenyl, 1-methyl-2-buten-1-yl, etc. Representative alkyne groups include, but are not limited to, ethynyl, 2-propynyl (propynyl), 1-propynyl, and other similar groups.

[0018] As used herein, the term "alicyclic" refers to a compound that combines the properties of aliphatic and cyclic compounds, and includes, but is not limited to, cyclic or polycyclic aliphatic hydrocarbons and bridging cycloalkyl compounds, which may optionally be substituted with one or more functional groups. As will be understood by those skilled in the art, the term "alicyclic" herein is understood to include, but is not limited to, cycloalkyl, cycloalkenyl, and cycloynyl groups, which may optionally be substituted with one or more functional groups. Therefore, examples of alicyclic groups include, but are not limited to, cyclopropyl, -CH2-cyclopropyl, cyclobutyl, -CH2-cyclobutyl, cyclopentyl, -CH2-cyclopentyl-n, cyclohexyl, -CH2-cyclohexyl, cyclohexenylethyl, cyclohexylethyl, norbornyl groups, etc., which may subsequently bear one or more substituents. The term "heteroaliphatic" refers to an aliphatic group in which one or more carbon atoms in the main chain have been replaced by heteroatoms. Therefore, a heteroaliphatic group refers to an aliphatic chain containing one or more oxygen, sulfur, nitrogen, phosphorus, or silicon atoms (i.e., replacing carbon atoms).

[0019] The terms “heterocyclic,” “heterocyclic alkyl,” or “heterocycle” refer to compounds that combine the properties of heterocyclic and cyclic compounds, and include, but are not limited to, saturated and unsaturated monocyclic or polycyclic heterocycles, such as morpholino, pyrrolidinyl, furanyl, thiofuranyl, pyrrolidinyl, etc., which are optionally substituted with one or more functional groups as defined herein. In some cases, the term “heterocycle” refers to a non-aromatic 5-, 6-, or 7-membered ring or polycyclic group, including, but not limited to, bicyclic or tricyclic groups comprising a fused six-membered ring having one to three heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein (i) each 5-membered ring has 0 to 2 double bonds and each 6-membered ring has 0 to 2 double bonds, (ii) the nitrogen and sulfur heteroatoms may optionally be oxidized, (iii) the nitrogen heteroatomium may optionally be quaternized, and (iv) any of the above heterocyclic rings may be fused with an aryl or heteroaryl ring. Representative heterocycles include, in particular, pyrrolidinyl, pyrazolinyl, pyrazolinyl, imidazolinyl, imidazolinyl, piperidinyl, piperazinyl, oxazolinyl, isoxazolinyl, morpholinyl, thiazolinyl, isothiazolinyl, and tetrahydrofuranyl.

[0020] As used herein, the term "aromatic group" refers to an unsaturated monocyclic or polycyclic hydrocarbon group, whether substituted or unsubstituted, that is stable and preferably has 3 to 14 carbon atoms and contains at least one ring conforming to the Hückel rule for aromaticity. Examples of aromatic groups include, but are not limited to, phenyl, indanyl, indenyl, naphthyl, phenanthryl, and anthraceneyl.

[0021] As used herein, the term "heteroaromatic group" refers to an unsaturated mono- or poly-heterocyclic group, whether substituted or unsubstituted, that is stable and preferably has 3 to 14 carbon atoms and contains at least one ring conforming to the Hückel rule for aromaticity. Examples of heteroaromatic groups include, but are not limited to, pyridinyl, quinolinyl, dihydroquinolinyl, isoquinolinyl, quinazolinyl, dihydroquinazolinyl, and tetrahydroquinazolinyl.

[0022] Aromatic and heteroaromatic groups as defined herein may be linked via aliphatic (e.g., alkyl) or heteroaliphatic (e.g., heteroalkyl) groups and thus via aromatic and heteroaromatic groups as defined herein (heteroalkyl), and therefore also include groups such as -(aliphatic)aromatic, -(heteroaliphatic)aromatic, -(aliphatic)heteroaromatic, -(heteroaliphatic)heteroaromatic, -(alkyl)aromatic, -(heteroalkyl)aromatic, -(alkyl)heteroaromatic, and -(heteroalkyl)heteroaromatic. Therefore, in this document, the terms "aromatic or heteroaromatic group" are interchangeable with "aromatic, heteroaromatic, -(alkyl)aromatic, -(heteroalkyl)aromatic, -(heteroalkyl)heteroaromatic, and -(heteroalkyl)heteroaromatic". Substituents include, but are not limited to, all of the aforementioned substituents that result in the formation of stable compounds.

[0023] The term "aryl" refers to an aromatic group. In some embodiments of the invention, the term "aryl" refers to a monocyclic or bicyclic carbocyclic system having one or two rings that conform to the Hückel rule of aromaticity, including but not limited to phenyl, naphthyl, tetrahydronaphthyl, indenyl, indenyl and other similar systems.

[0024] Similarly, the term "heteroaryl" refers to a heteroaryl group. In some embodiments of the invention, as used herein, the term "heteroaryl" refers to an unsaturated cyclic group in which one atom of the ring is selected from S, O, and N; the ring may contain zero, one, or two additional heteroatoms independently selected from S, O, and N; and the remaining ring atoms are carbon atoms, and the group is connected to the rest of the molecule via any of the ring atoms to form a group such as pyridyl, pyrazinyl, pyrimidinyl, pyrroleyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, thiophene, furanyl, quinolinyl, isoquinolinyl, etc.

[0025] Substituents on the aryl and heteroaryl groups include, but are not limited to, all of the aforementioned substituents, i.e., substituents listed for aliphatic groups or other groups, to form a stable compound. In some cases, the aliphatic group contains 1 to 12 aliphatic carbon atoms. In other cases, the aliphatic group contains 6 to 10 aliphatic carbon atoms. In yet another embodiment, the aliphatic group contains 4 to 10 aliphatic carbon atoms. For example, the term "C 1-12 "Alkyl" is defined as an alkyl group having 1 to 12 carbon atoms; this naming rule also applies to "C 2-12"Alkenyl", C 2-12 Alkenyl groups refer to alkenyl groups having 2 to 12 carbon atoms, and can be extended to other aliphatic groups, such as alkynyl and heteroalkyl groups.

[0026] The terms "alkoxy" (or "alkyloxy") and "thioalkyl" refer to an alkyl group as defined above, which is partially attached to a parent molecule via an oxygen atom ("alkoxy") or a sulfur atom ("thioalkyl"). Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, tert-butoxy, neopentoxy, and n-hexyloxy. Examples of thioalkyl groups include, but are not limited to, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, etc.

[0027] As used herein, the term "hydroxyl" refers to a group having the structure -OH, and as used herein, unless otherwise specified, the term "hydroxyl protecting group" refers to a substituent commonly used to block or protect a hydroxyl group on a compound, thus preserving its functional group while allowing other functional groups on the compound to react. Non-exhaustive examples of hydroxyl protecting groups include: acyl groups (e.g., formyl, acetyl, chloroacetyl, trichloroacetyl, o-nitrophenylacetyl, o-nitrophenoxyacetyl, trifluoroacetyl, acetoacetyl, 4-chlorobutyryl, isobutyryl, o-nitrocinnamyl, pyridinecarboxyl, acyl isothiocyanate, aminohexanoyl, benzoyl, etc.), acyloxy groups (e.g., 1-tert-butoxycarbonyl (Boc), methoxycarbonyl, 9-fluorenyl-methoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, 2-trimethylsilyloxycarbonyl, ethyleneoxycarbonyl, allyloxycarbonyl, 1,1-dimethylpropynyloxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, etc.), diphenylmethane, silyl ethers (e.g., tert-butyldimethylsilyl ether, abbreviated as "TBS"), and benzyl carbamate. As used herein, “hydroxyl group deprotection” refers to a chemical reaction involving a deprotecting agent to remove substituents previously used to protect the hydroxyl group. The term “amine” refers to a group having the structure -N(R)2, wherein each R is independently hydrogen or an aliphatic, heteroaliphatic, aromatic, or heteroaromatic group, or the R groups together can form a heterocyclic group.

[0028] The term "alkylamino" refers to a group having the structure -NHR', where R' is an alkyl group as defined herein. The term "aminoalkyl" refers to a group having the structure NH2R'-, where R' is an alkyl group as defined herein. In some cases, the hydrocarbon group contains about 1 to 20 aliphatic carbon atoms. In other cases, the hydrocarbon group contains about 1 to 10 aliphatic carbon atoms. In still other cases, the alkyl, alkenyl, and alkynyl groups used in this invention contain about 1 to 8 aliphatic carbon atoms. In yet other embodiments, the alkyl group contains about 1 to 6 aliphatic carbon atoms. In yet other embodiments, the alkyl group contains about 1 to 4 aliphatic carbon atoms. Examples of alkylamino groups include, but are not limited to, methylamino, ethylamino, isopropylamino, etc.

[0029] As used herein, unless otherwise specified, the term "amine protecting group" refers to a substituent commonly used to block or protect an amine on a compound, thus preserving its functional group while allowing other functional groups on the compound to react. Non-exhaustive examples of amine protecting groups include: acyl groups (e.g., formyl, acetyl, chloroacetyl, trichloroacetyl, o-nitrophenylacetyl, o-nitrophenoxyacetyl, trifluoroacetyl, acetoacetyl, 4-chlorobutyryl, isobutyryl, o-nitrocinnamyl, pyridinecarboxyl, acyl isothiocyanate, aminohexanoyl, benzoyl, etc.), acyloxy groups (e.g., 1-tert-butoxycarbonyl (Boc), methoxycarbonyl, 9-fluorenyl-methoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, 2-trimethylsilyl-ethoxycarbonyl, ethyleneoxycarbonyl, allyloxycarbonyl, 1,1-dimethyl-propynyloxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, etc.), diphenylmethane, and benzyl carbamate.

[0030] As used in this article, the terms “halogenated” and “halogen” refer to atoms selected from fluorine, chlorine, bromine, and iodine.

[0031] The term "halogenation" refers to the attachment of one, two, or three halogen atoms to a portion of a molecule.

[0032] The term "halogenated alkyl" refers to one, two, or three halogen atoms attached to an alkyl group as defined above, and is exemplified by groups such as chloromethyl, bromoethyl, and trifluoromethyl.

[0033] As used herein, the term "acyloxy" has no substantial difference from its common meaning in the art and refers to the structural moiety -OC(O)RX, wherein RX is a substituted or unsubstituted aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, or heteroaryl moiety. As used herein, the term "acyl" has no substantial difference from its common meaning in the art and refers to the structural moiety -C(O)RX, wherein RX is a substituted or unsubstituted aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, or heteroaryl moiety.

[0034] As used herein, the term "imino" is not substantially different from its common meaning in the art and refers to the structural group -C(=NRX)RY, wherein RX is hydrogen or an optionally substituted aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, or heteroaryl group, and RX is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, or heteroaryl group.

[0035] Unless otherwise stated, the term "sulfonate leaving group" as used herein refers to an anion having the general formula RSO2O-. Non-limiting examples of sulfonate leaving groups include: methanesulfonates (R = CH3); trifluoromethanesulfonates (R = CF3); and toluenesulfonates (R = CH3C6H4, abbreviated as "Ts"), such as p-toluenesulfonates (p-Ts).

[0036] In this specification, the terms "aliphatic," "heteroaliphatic," "alkyl," "alkenyl," "alkynyl," "heteroalkyl," "heteroalkenyl," "heteroalkynyl," and similar terms encompass both substituted and unsubstituted, saturated and unsaturated, straight-chain and branched groups. Similarly, the terms "alicyclic," "heterocyclic," "heterocyclic alkyl," "heterocyclic," etc., encompass both substituted and unsubstituted, saturated and unsaturated groups. Furthermore, the terms "cycloalkyl," "cycloalkenyl," "cycloalkynyl," "heterocyclic alkyl," "heterocyclic alkenyl," "heterocyclic alkenyl," "aromatic," "heteroaromatic," "aryl," "heteroaryl," and other similar terms, used alone or as part of a larger group, encompass both substituted and unsubstituted groups. Summary of the Invention

[0037] The present invention aims to overcome the aforementioned drawbacks by implementing an alternative method for preparing synthetic intermediates that are suitable for a wide range of applications in total synthesis.

[0038] Therefore, the present invention relates to a method for preparing trifluoroethyleneamine of formula (II) by using a molecule of formula (I) in n steps, wherein n is equal to 1 or 2:

[0039] Wherein groups R1 and R2 together form a heterocycle or independently represent functional groups selected from hydrogen and aliphatic chains, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-12 Alkyl, C 1-12 Heteroalkyl, C 6-10 Aryl and C 4-10 A heteroaryl group; each of the alkyl, heteroalkyl, aryl, and heteroaryl groups defined above optionally comprises one or more substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; and R1 and R2 preferably represent branched or cyclic alkyl chains; and wherein X is a halogen, preferably selected from -F and -Cl, wherein the method implements the reaction of the compound of formula (I) with the compound of formula (V): , or the reaction of a compound of formula (I) with a compound of formula (III); To form a compound of formula (IV): The compound of formula (IV) reacts with the compound of formula (V) to form the compound of formula (II); all reactions are preferably carried out in a solvent containing THF; and the metal M is preferably selected from Li and Na.

[0040] The number of steps performed in the method according to the invention is n, where n is an integer greater than or equal to 1; and n is chosen to be less than 5. Preferably, n is less than 4, and advantageously, n is less than 3 or between 1 and 2.

[0041] Preferably, the halogen in group X of the compound of formula (I) is fluorine-F, in which case compound (I) is a molecule of trifluoromethane.

[0042] The inventors unexpectedly discovered that, despite significant steric hindrance, compound (II) can be prepared from trifluoromethane or from one of its halogenated derivatives. According to one embodiment, a method for preparing trifluoroethyleneamine of formula (II) comprises the step of converting trifluoromethane (Ia) via the following synthetic route to produce the intermediate Me3SiCF3 (IV): , Such synthetic routes advantageously consist of two steps, which makes it possible to limit the reaction sequence required to produce the target molecule. Preferably, steps 1- and 2- are carried out in a solvent containing THF or even only THF; and the metal M in the alkylamide of formula (V) is preferably an alkali metal, which is advantageously selected from Li and Na.

[0043] According to another embodiment, the method for preparing trifluoroethyleneamine of formula (II) according to the present invention comprises the following synthetic route:

[0044] This synthetic route advantageously consists of a single step that directly produces the target molecule.

[0045] According to the synthetic route previously described in the context of this invention, the one-step synthesis of trifluoroethyleneamine of formula (II) employs a compound of formula (V) containing a metal M, preferably an alkali metal, advantageously selected from Li and Na; and the reaction solvent advantageously contains THF, or even consists entirely of THF.

[0046] To improve reaction conditions, and especially to increase yield, THF can be wholly or partially replaced by other suitable solvents (such as hexane and / or diethyl ether).

[0047] Preferably, the preparation method according to the invention more specifically produces compounds of the following formulas (IIa-IIb):

[0048] Preferably, the compound (V) that can be used to synthesize trifluoroethyleneamine of formula (II) corresponds to the following formula and is lithium amide:

[0049] These lithium amides are well known and specifically described in the book by M. Lappert, A. Protchenko, P. Power, and A. Seeber entitled “Metal Amide Chemistry”, published by Wiley, New York, 2008 (see page 7 in particular).

[0050] Implementing the one-step or two-step synthetic routes previously described within the scope of this invention offers significant advantages: it enables the acquisition of all target compounds of formula (II) starting from alkyl lithium amides of formula (V) (e.g., alkyl lithium amides derived from dicyclohexylamine, 2,2,6,6-tetramethylpiperidine, dimethylamine, diethylamine, diisopropylamine, N-methylaniline, carbazole, or 2-pyrrolidine). This invention also relates to novel synthetic routes employing at least one of the compounds of formula (II) described above within the scope of this invention and comprising the following steps:

[0051] R3 is a functional group selected from hydrogen and an aliphatic chain, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-12 Alkyl, C 1-12 Heteroalkyl, C 6-10 Aryl and C 4-10 The heteroaryl group; each of the alkyl, heteroalkyl, aryl, and heteroaryl groups optionally comprises one or more substituents, the substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO3-; -SO2-; -C(=O)O-; -C(=O)S- and -C(=O)N-; Wherein Q represents a functional group selected from hydrogen and substituents containing elements with electronegativity less than that of carbon, particularly a metal M', wherein M' is preferably selected from Mg and Li.

[0052] Electronegativity refers to Pauling electronegativity; and carbon has an electronegativity of 2.55. Preferably, the aforementioned method for synthesizing the compound according to formula (VI), including the aforementioned m synthetic steps, implements the method for preparing the compound of formula (II) previously described within the scope of the invention. The number of steps implemented in the method for synthesizing (VI) according to the invention is m, where m is an integer greater than or equal to 1; and m is chosen to be less than 5. Preferably, m is less than 4 or is 1 to 3. Preferably, the method for synthesizing the compound of formula (VI) according to the invention relates to the synthesis of the compound of formula (VI.1):

[0053] Among them, the substituent Ar 1 Selected from C 6-10 Aryl and C 4-10Heteroaryl groups; each of the aryl and heteroaryl groups defined above with respect to compound (VI.1) optionally comprises one or more substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; and Preferably, compound (VI.1) is selected from the following compounds (VIa-VIh):

[0054] The present invention also relates to a novel synthetic route employing at least one of the compounds of formula (II) described above within the scope of the present invention and comprising the following steps:

[0055] R5 and R6 independently represent functional groups selected from hydrogen and aliphatic chains, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-12 Alkyl, C 1-12 Heteroalkyl, C 6-10 Aryl and C 4-10 The heteroaryl group; each of the alkyl, heteroalkyl, aryl and heteroaryl groups optionally comprises one or more substituents, the substituents comprising at least one atom or functional group selected from the following: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-.

[0056] Preferably, the aforementioned method for synthesizing the compound according to formula (VIII), including the q synthetic steps, implements the method for preparing the compound of formula (II) previously described within the scope of the invention.

[0057] The number of steps performed in the method for synthesizing (VIII) according to the invention is q, where q is an integer greater than or equal to 1; and p is selected to be less than 5. Preferably, p is selected to be less than 4 or between 1 and 3. Preferably, the method for synthesizing compounds of formula (VIII) according to the invention relates to the synthesis of compounds of formulas (VIIIa-VIIId):

[0058] This invention also relates to the following novel synthetic routes: these novel synthetic routes employ at least one of the compounds of formula (II) described above within the scope of this invention, and include a reaction step between compound (II) and an ortho-disubstituted aromatic compound or even an ortho-disubstituted heteroaromatic compound, such that one substituent of the aromatic or heteroaromatic compound comprises a -N- atom, and the other substituent comprises a -O-, -N-, -S-, and / or -Se- atom; preferably, the synthetic route includes the following steps and employs the following aromatic hydrocarbons:

[0059] Preferably, the aforementioned method for synthesizing the compound according to formula (IX) implements the method for preparing the compound of formula (II) previously described within the scope of the invention. The invention also relates to novel synthetic routes employing at least one of the compounds of formula (II) described above within the scope of the invention according to the following reactions: , The methyl group on the nitrogen atom of the compound reacting with TFVA may optionally be replaced independently of each other by other substituents such as ether groups (e.g., MeO-), ester groups, etc. According to another aspect, the present invention relates to compounds obtained from or capable of being obtained from trifluoromethane of formula (I) using the methods described within the scope of the invention for preparing compounds of formula (II), said compounds being represented by the following general formula (IIc):

[0060] Among them, groups R7, R8, and R 11 and R 12 Independently representing a functional group selected from hydrogen and an aliphatic chain, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-12 Alkyl, C 1-12 Heteroalkyl, C 6-10 Aryl and C 4-10 The heteroaryl group; each of the alkyl, heteroalkyl, aryl, and heteroaryl groups optionally comprises one or more substituents, the substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; Groups R9 and R 10 : - When used, it is indicated independently, such as for groups R7, R8, R 11 and R 12 Defined functional groups; - Together, they represent a single cyclic aliphatic chain containing groups R9 and R. 10 The C atom and the R9 and R 10 The N atom is attached to the C atom; wherein the cyclic aliphatic chain is selected from C 1-12 Alkyl, C 1-12 The heteroalkyl group, each of the alkyl and heteroalkyl groups defined above, optionally comprises one or more substituents, the substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3; -C(=O)O-; -C(=O)S- and -C(=O)N-; Excluding compounds (IId-IIf) in which groups R7, R8, and R... 11 and R 12 Selected from four hydrogens, and the groups R9 and R 10 Included in the nitrogen-containing rings identified in (IId-IIf):

[0061] Preferably, the compound of formula (IIc) according to the invention is selected from the following compounds (IIa-IIb):

[0062] Compounds of formula (II) allow for one-step synthetic schemes of compounds containing CF2 groups; such schemes typically involve two or more steps. Compounds of formula (II) exhibit unique reactivity to fluorinated compounds in the presence of Lewis acids. Typically, compounds of formula (II) can be reacted with nucleophiles in the presence of Lewis acids to produce difluoroenamine-type substances that are detectable by NMR and are generally separable; these substances can then be functionalized. Furthermore, compounds of formula (II) can be used to synthesize novel compounds, such as those of formulas (VIe), (VIIIa), and (VIIIc) described above. The invention is also described in a detailed description below using an experimental section, which details certain embodiments using examples given by way of illustration only and should not be considered limiting.

[0063] Experimental Section Experimental equipment and scheme Unless otherwise specified, all reactions were carried out using oven-dried glassware and under argon and magnetic stirring. Reaction temperatures were specified as the bath temperature around the container. Analytical thin-layer chromatography was performed on aluminosilicate plates using F-254 indicator and visualized under UV light (254 nm) and / or with chemical staining in KMnO4 or ninhydrin solution. Rapid column chromatography was performed using silica gel with a particle size of 0.040 nm–0.063 nm. The spectrometer was Bruker DXP 300 MHz. 1 The H NMR spectra were recorded at 300.1 MHz. 13 The C NMR spectrum was recorded at 75.5 MHz, and 19 The F NMR spectrum was recorded at 282.4 MHz. Compared to TMS ( 1 H) and CFCl3 ( 19 F), chemical shift (δ) is given in ppm. Coupling constant (J) is expressed in Hz. The following abbreviations are used to indicate multiplicity: s: singlet, d: doublet, t: triplet, q: quartet, dd: doublet, ddd: doublet doublet, dt: triplet doublet, m: multiplet. The signal from the residual solvent is used as a reference (CDCl3: δH = 7.26ppm, δC = 77.16ppm; (CD3)2SO: δH = 2.50ppm, δC = 39.52ppm or relative to the external standard CFCl3, δF = 0ppm). High-resolution mass spectrometry (HRMS) was performed using an electrospray ionization mass spectrometer equipped with a micro TOF analyzer. Infrared spectra were recorded using a PerkinElmer Paragon 100 FT-IR spectrometer (ATR); the wavenumber (□) of the recorded IR signal (ATR) is expressed in cm⁻¹. 1 The melting point was measured in an open capillary using a STUART SMP3 apparatus.

[0064] Example Part 1: Preparation of dicyclohexyl(trifluorovinyl)amine of formula IIb

[0065] Two solutions have been prepared: - Solution A: 300 mL of 0.3 M CHF3 THF solution, prepared by saturating THF with CHF3 at 0 °C and ambient pressure, followed by stirring at 20 °C for 2 hours.

[0066] Solution B: 300 mL of 0.5 M Cy₂NLi (Va) solution, diluted by adding 60 mL of 2.5 M solution. n- The preparation is achieved by adding a BuLi hexane solution to 30 mL of a dicyclohexylamine solution in 210 mL of THF.

[0067] Both solutions A and B were pumped at a rate of 5 mL / min (using Syrris ASIA). ™ The mixture was pumped into a flow cell (ID 1.6 mm) consisting of two 2 mL precooling tubes, followed by a T-joint mixer and a 1 mL reaction tube. The entire system was immersed in an ice bath. The reactor outlet was inserted into a 1 L flask containing a stir bar (under an argon atmosphere) (cooled in an ice bath). After decanting the first 40 mL of the resulting mixture, the residue was collected. The resulting mixture was stirred at room temperature for 8 hours.

[0068] Neutral alumina (approximately 300 g) was washed with ethyl acetate and added to the mixture, followed by an equal volume of petroleum ether. The entire mixture was then filtered through a sintered glass filter; the solids were washed with another volume of petroleum ether. The filtrate was washed with 10% H3PO4 aqueous solution (3 × 150 mL), saturated NaHCO3 solution (100 mL), and saturated NaCl solution (150 mL). The organic phase was concentrated and washed with petroleum ether on a neutral alumina pad (600 g; pre-washed with ethyl acetate and then with petroleum ether). The product was eluted with petroleum ether, concentrated, and dried under vacuum. Yellow liquid. 5.2 g (40% yield). The product obtained after washing with water can also be purified by vacuum distillation (42℃–46℃, 0.1 mbar).

[0069] Compound IIb can also be prepared from TMSCF3 using the same apparatus (molar ratio of TMSCF3 to Cy2NLi = 2.5:1; T = 36 °C, 1 mL / min for each solution).

[0070] 1 H NMR (300MHz, CDCl3) δ 2.76 – 2.63 (m, 2H), 1.66 (m, 8H), 1.51 –1.43 (m, 2H), 1.18 – 0.90 (m, 10H). 19 F NMR: -106.9 (dd, J = 67, 37Hz, 1 F), -117.4 (dd, J = 118, 37Hz, 1 F), 118.1 (dd, J = 118, 67Hz, 1 F).

[0071] Part 2: Dicyclohexyl(trifluorovinyl)amine of formula (IIb) and N-(trifluorovinyl)-2,2, Preparation of 6,6-tetramethylpiperidine; Comparison of different conditions Tables 1 and 2 below summarize the four syntheses performed according to method A or method B, along with the products and yields obtained (Table 1). Table 2 lists the optimal conditions for testing.

[0072] Table 1

[0073] Table 2

[0074] The term "yield 1" refers to R2NLi-based yield. 19 F NMR yield.

[0075] The term "yield 2" refers to CF-based yield 2. 3 Y's 19 F NMR yield.

[0076] Method A: 3 R₂NLi + 2 CHF₃ -> R₂N-CF = CF₂ + 2 R₂NH + 1 LiF Method B: 1 R2NLi + 2 TMSCF3>R2N-CF=CF2+ 2 TMSF + 1 LiF

[0077] "Batch" conditions: Using a syringe, rapidly add solution A (1 mL) to a sealed tube containing solution B and stir at the specified temperature. Heat the mixture to room temperature and then add an internal standard. Transfer the mixture to an NMR tube with a diaphragm that has been pre-inertized with N2.

[0078] Prepared according to the continuous flow method described for dicyclohexyl(trifluorovinyl)amine (IIb) (Formula IIa) N- (trifluorovinyl)-2,2,6,6-tetramethylpiperidine. 1 H NMR (300MHz, CDCl3) δ 1.61 – 1.38 (m, 6H), 1.29 (s, 6H), 1.14 (s, 6H).

[0079] 19 F NMR (282MHz, CDCl3) δ -109.58 (dd, J = 70.0, 34.4Hz), -116.79 (dd, J =116.2, 70.0Hz), -123.12 (dd, J = 116.3, 34.5Hz) Part 3: Synthesis of Other Trifluoroethyleneamines Other compounds of formula (II) were also synthesized according to the following schemes: Compound IIb prepared from sodium amide: 8.5 g of a 30% (w / w) Na dispersion in toluene was added to a 100 mL double-necked flask equipped with a filter suitable for argon filtration, a stir bar, and a diaphragm, and then purged with argon. An argon balloon was connected via the diaphragm. Cyclohexane (30 mL), Cy2NH (32 mL), and isoprene (17 mL) were added to the flask sequentially. The mixture was sonicated for 3 hours and then stirred at room temperature for 18 hours. During this stage, a large amount of white precipitate was observed. To promote complete sodium conversion, multiple cycles of sonication and stirring can be applied.

[0080] The mixture was then filtered under argon atmosphere. The recovered solid was washed with 50 mL of cyclohexane and dried under vacuum (0.1 mbar) without exposure to the ambient atmosphere. The dried white solid (12 g) was stored in a glove box. The purity of Cy2NNa was determined by titration with a THF solution of N-benzylbenzamide at 0 °C.

[0081] For the synthesis of IIb, Cy2NNa was dissolved in THF (0.25 M) at 0 °C under argon atmosphere and then maintained at -20 °C throughout the procedure. The continuous-flow synthesis of IIb using Cy2NNa was carried out in the same manner as previously described for Cy2NLi (reactor and pre-cooled tubing immersed in an ice bath), using a Syrris ASIA pump and supplying the Cy2NNa solution directly from a cooled reservoir. Using this procedure, a flow rate of 2 mL / min for CHF3 solution and 4 mL / min for Cy2NNa solution yielded a 32% IIb yield (measured by fluorine-19 NMR with 4-fluorotoluene as an internal standard, D1 = 10 s).

[0082] Compound IId: 1.1 mmol of n-butyllithium (in 2.4 M hexane) was added dropwise to a stirred solution of 1.1 mmol of isopropylamine in 3 mL of THF (cooled in an ice bath). After 10 minutes, 2.1 mmol of TMSCF3 was added in a single addition. A dark gray color appeared immediately, which rapidly turned dark brown. The mixture gelled. After 20 minutes at room temperature, 0.5 mL was mixed with EtOAc-saline. 20 μL of 4-fluorotoluene (0.18 mmol) was added as an internal standard, and the yield was determined by fluorine-19 NMR.

[0083] Compound IIe: 1.1 mmol of n-butyllithium (in 2.4 M hexane) was added dropwise to a stirred solution of 1.1 mmol of N-methylaniline in 3 mL of THF (cooled in an ice bath). A turbid solution formed. After 15 minutes, 2.1 mmol of TMSCF3 was added in a single addition. The initially turbid solution became clear, and a light-colored precipitate appeared. After 30 minutes at room temperature, 0.5 mL was mixed with EtOAc-saline. 20 μL of 0.18 mmol of 4-fluorotoluene was added as an internal standard, and the yield was determined by fluorine-19 NMR.

[0084] Compound IIf: 1.1 mmol of n-butyllithium (in 2.4 M hexane) was added dropwise to a stirred solution of 1.1 mmol of N-allylaniline in 3 mL of THF (cooled in an ice bath). After 15 minutes, 2.1 mmol of TMSCF3 was added in a single addition. A dark gray color appeared briefly, then returned to a pale yellow hue. After 20 minutes at room temperature, 0.5 mL was mixed with EtOAc-saline. 20 μL of 4-fluorotoluene (0.18 mmol) was added as an internal standard, and the yield was determined by fluorine-19 NMR.

[0085] Compound IIg: 1.1 mmol of n-butyllithium (in 2.4 M hexane) was added dropwise to a stirred solution of 1.1 mmol of carbazole in 3 mL of THF (cooled in an ice bath). A turbid solution formed. After 15 minutes, 2.1 mmol of TMSCF3 was added in a single addition. After 16 hours at room temperature, 0.5 mL was mixed with EtOAc-saline. 20 μL of 4-fluorotoluene (0.18 mmol) was added as an internal standard, and the yield was determined by fluorine-19 NMR.

[0086] Compound IIh: Butyllithium (1.1 mmol in 2.4 M hexane solution) was added dropwise to a stirred solution of pyrrolidone (1.1 mmol) in 3 mL THF (cooled in an ice bath). After 15 minutes, TMSCF3 (2.1 mmol) was added in a single addition. After 16 hours at room temperature, 0.5 mL was mixed with EtOAc-saline. 20 μL of 4-fluorotoluene (0.18 mmol) was added as an internal standard, and the yield was determined by fluorine-19 NMR.

[0087] These compounds are grouped together in Table 3 below.

[0088] Table 3

[0089] Part 4: General Scheme for the Reaction between Dicyclohexyl(trifluorovinyl)amine and Nucleophiles Dicyclohexyl(trifluorovinyl)amine (100 mg, 0.38 mmol) was dissolved in anhydrous DCM (2.5 mL) under argon atmosphere. A nucleophile (aromatic, sulfoxide, based on the desired final compound) (0.32 mmol) was added. The mixture was cooled to -78 °C. BF3-Et2O (54 mg, 47 mL, 0.38 mmol) was added dropwise. The mixture was warmed to room temperature and stirred for 1 hour. The mixture was diluted with ethyl acetate (10 mL), washed with saturated NaHCO3 solution (5 mL) and saturated NaCl solution (5 mL), dried over MgSO4, and evaporated. The product was purified by column chromatography.

[0090] Part 5: Dicyclohexyl(trifluorovinyl)amine with substitutions selected from electron-donating groups (EDG; abbreviated as "EDG"). Reaction schemes and results obtained for reactions between nucleophiles of aromatic compounds

[0091] result :

[0092] Part 6: Reactions between dicyclohexyl(trifluorovinyl)amine and nucleophiles selected from alkynes The plan and the results obtained

[0093] For compounds (VIIIa) to (VIIId), yields exceeding 50% were obtained.

[0094] Characterization of the obtained compounds : (VIa) 1 H NMR (300MHz, CDCl3) δ 3.89 (s, 3 H), 6.27 (t, J = 54Hz, 1H), 6.98 (m, 2H), 8.06 (m, 2H); 19 F NMR (282MHz, CDCl3) δ -121.4 (d, J = 54Hz).

[0095] (VIc) 1 H NMR (300MHz, CDCl3) δ 3.28 (t, J = 8.8Hz, 2 H), 4.70 (t, J =8.8Hz, 2 H), 6.25 (t, J = 54Hz, 1 H), 6.86 (d, J = 9.4Hz, 1 H), 7.93 (d, J = 9.4Hz,1H), 7.94 (s, 1H);19 ¹⁹F NMR (282 MHz, CDCl₃) δ -121.1 (d, J J = 54 Hz).

[0096] (VId) 1 ¹H NMR (300 MHz, CDCl₃) δ 6.08 (s, 2 H), 6.23 (t, J J = 54 Hz, 1 H), 6.90 (d, J J = 8.0 Hz, 1 H), 7.49 (s, 1 H), 7.70 (d, J J = 8.0 Hz, 1 H); 19 ¹⁹F NMR (282 MHz, CDCl₃) δ -121.1 (d, J J = 54 Hz).

[0097] (VIe) 1 ¹H NMR (300 MHz, CDCl₃) δ 8.00 (d, J J = 9.0 Hz, 2H), 6.88 (d, J J = 9.0 Hz, 2H), 6.24 (t, J J = 53.9 Hz, 1H), 3.91 – 3.80 (m, 4H), 3.43 – 3.30 (m, 4H).; 19 ¹⁹F NMR (282 MHz, CDCl₃) δ -121.1 (d, J J = 54 Hz).

[0098] (VIh) 1 ¹H NMR (300 MHz, CDCl₃) δ 6.86 (t, J J = 53.5 Hz, 1 H), 7.32 (dd, J J = 8.5 and 1.9 Hz, 1 H), 7.63 (d, J J = 1.9 Hz, 1 H), 8.16 (d, J J = 8.5 Hz, 1 H), 8.53 (s, 1 H), 12.52 (br.s, 1H); 19 ¹⁹F NMR (282 MHz, CDCl₃) δ -124.2 (d, J J = 53.5 Hz).

[0099] (VIIIa) 1¹H NMR (300 MHz, DMSO-d₆) δ 7.82 (d, J J = 16.1 Hz, 1H), 7.53 – 7.47 (m, 2H), 7.43 – 7.34 (m, 2H), 6.95 (dt, J J = 16.1, 1.2 Hz, 1H), 5.86 (t, J J = 54.1 Hz, 1H), 1.27 (s, 9H); 19 ¹⁹F NMR (282 MHz, DMSO-d₆) δ -121.01 (d, J J = 54.2 Hz).

[0100] (VIIIb) 1 ¹H NMR (300 MHz, DMSO-d₆) δ 5.93 (t, J J = 54 Hz, 1 H), 7.03 (dt, J J = 16.1 and 1.0 Hz, 1 H), 7.17 (m, 1 H), 7.32 (m, 1 H), 7.41 (m, 2 H), 7.84 (d, J J = 16.1 Hz); 19 ¹⁹F NMR (282 MHz, DMSO-d₆) δ -112.4 (m, 1 F), -126.6 (d, J J = 54 Hz, 2 F).

Claims

1. A method for preparing trifluoroethyleneamine of formula (II) using a molecule of formula (I), wherein n = 1 or 2: Wherein groups R1 and R2 together form a heterocycle or independently represent functional groups selected from hydrogen and aliphatic chains, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-12 Alkyl, C 1-12 Heteroalkyl, C 6-10 Aryl and C 4-10 Heteroaryl groups; each of the alkyl, heteroalkyl, aryl, and heteroaryl groups defined above optionally comprises one or more substituents, said substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; R1 and R2 preferably represent branched or cyclic alkyl chains; and wherein X is a halogen, preferably selected from -F and -Cl, The method describes the reaction of the compound of formula (I) with the compound of formula (V): The reaction of a compound of formula (I) with a compound of formula (III): To form a compound of formula (IV): The compound of formula (IV) reacts with the compound of formula (V) to form the compound of formula (II); all reactions are preferably carried out in a solvent containing THF; and the metal M is preferably selected from Li and Na.

2. The method according to claim 1, characterized in that... X is a fluorine atom, and the method therefore carries out the following two reactions: ； Steps 1 and 2 are preferably carried out in a solvent containing THF, and the metal M is preferably selected from Li and Na.

3. The method for preparing a compound of formula (II) according to claim 1, characterized in that... X is a fluorine atom, and the method performs the following reaction, The metal M is preferably an alkali metal, advantageously selected from Li and Na; and the reaction solvent contains THF.

4. The method for preparing a compound of formula (II) according to any one of claims 1 to 3, wherein compound (II) is selected from the group consisting of compounds (IIa-IIb): 。 5. A method for synthesizing a compound according to formula (VI), said method carrying out the method for preparing a compound of formula (II) according to any one of claims 1 to 4, and comprising the following subsequent steps: Wherein R3 is a functional group selected from hydrogen and an aliphatic chain, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-12 Alkyl, C 1-12 Heteroalkyl, C 6-10 Aryl and C 4-10 The heteroaryl group; each of the alkyl, heteroalkyl, aryl, and heteroaryl groups optionally comprises one or more substituents, said substituents comprising at least one atom or functional group selected from the following: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; Q represents a functional group selected from hydrogen and substituents containing elements with electronegativity less than that of carbon, particularly a metal M', wherein M' is preferably selected from Mg and Li; and m is an integer less than 5, preferably 1 to 3.

6. The method for synthesizing a compound according to claim 5, wherein the compound of formula (VI) is a compound of formula (VI.1): Among them, the substituent Ar 1 Selected from C 6-10 Aryl and C 4-10 The heteroaryl group; each of the aryl and heteroaryl groups optionally comprises one or more substituents, the substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; and Preferably, (VI.1) is selected from the following compounds (VIa-VIh): 。 7. A method for synthesizing a compound according to formula (VIII), said method carrying out the method for preparing a compound of formula (II) according to any one of claims 1 to 4, and comprising the following subsequent steps: R5 and R6 independently represent functional groups selected from hydrogen and aliphatic chains, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-12 Alkyl, C 1-12 Heteroalkyl, C 6-10 Aryl and C 4-10 Heteroaryl groups; each of the alkyl, heteroalkyl, aryl, and heteroaryl groups optionally comprises one or more substituents, said substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; - OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; and q is an integer less than 5, preferably 1 to 3.

8. The method for synthesizing a compound according to claim 7, wherein the compound of formula (VIII) is selected from the group of compounds (VIIIa–VIIId): 。 9. A method for synthesizing a compound according to formula (IX), said method being carried out via the following reaction: a method for preparing a compound according to any one of claims 1 to 4: 。 10. A method for synthesizing a compound according to formula (X), said method being carried out via the following reaction: a method for preparing a compound according to any one of claims 1 to 4: 。 11. A compound obtained from trifluoromethane of formula (I) using the method according to any one of claims 1 to 4, said compound being represented by the following general formula (IIc): Among them, groups R7, R8, and R 11 and R 12 Independently representing a functional group selected from hydrogen and an aliphatic chain, wherein the aliphatic chain is selected from at least one of the following chains: straight chain, branched chain, cyclic chain, substituted or unsubstituted chain; wherein the aliphatic chain is selected from C 1-11 Alkyl, C 1-11 Heteroalkyl, C 6-9 Aryl and C 4-9 The heteroaryl group; each of the alkyl, heteroalkyl, aryl, and heteroaryl groups optionally comprises one or more substituents, said substituents comprising at least one atom or functional group selected from the following: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO2-; -SO3-; -C(=O)O-; -C(=O)S- and -C(=O)N-; Groups R9 and R 10 : - When used, it is indicated independently, such as for groups R7, R8, R 11 and R 12 Defined functional groups; - Together, they represent a single cyclic aliphatic chain, the single cyclic aliphatic chain comprising the groups R9 and R... 10 The C atom and the R9 and R 10 The N atom attached to the C atom; wherein the cyclic aliphatic chain is selected from C 1-12 Alkyl, C 1-12 The heteroalkyl group, each of which optionally comprises one or more substituents, the substituents comprising at least one atom or functional group selected from: -F; -Cl; -Br; -I; -NO2; -CN; -CF3; -OH; -O-; -S-; -C(=O)-; -S(=O)-; -SO3-; -SO2; -C(=O)O-; -C(=O)S- and -C(=O)N-; Excluding compounds (IId-IIf) in which groups R7, R8, and R... 11 and R 12 Selected from four hydrogens, and the groups R9 and R 10 Included in the nitrogen-containing rings identified in (IId-IIf): 。 12. The compound according to claim 11, wherein the compound of formula (IIc) is selected from the following compounds (IIa-IIb): 。

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