WO2019061299A1 - Process for preparing aminomethyl substituted heterocycloalkane - Google Patents

Process for preparing aminomethyl substituted heterocycloalkane Download PDF

Info

Publication number
WO2019061299A1
WO2019061299A1 PCT/CN2017/104404 CN2017104404W WO2019061299A1 WO 2019061299 A1 WO2019061299 A1 WO 2019061299A1 CN 2017104404 W CN2017104404 W CN 2017104404W WO 2019061299 A1 WO2019061299 A1 WO 2019061299A1
Authority
WO
WIPO (PCT)
Prior art keywords
heterocycloalkane
functional group
ammonia
substituted
process according
Prior art date
Application number
PCT/CN2017/104404
Other languages
French (fr)
Inventor
Fan Jiang
Stéphane STREIFF
Bing HONG
Original Assignee
Rhodia Operations
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Rhodia Operations filed Critical Rhodia Operations
Priority to PCT/CN2017/104404 priority Critical patent/WO2019061299A1/en
Publication of WO2019061299A1 publication Critical patent/WO2019061299A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/06—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
    • C07D305/02—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D305/04—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D305/06—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02—Seven-membered rings
    • C07D313/04—Seven-membered rings not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/02—1,2-Dioxanes; Hydrogenated 1,2-dioxanes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/12—Radicals substituted by halogen atoms or nitro or nitroso radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/02—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/02—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/08—Six-membered rings

Definitions

  • the present invention relates to a one-step amination reaction for producing an aminomethyl substituted heterocycloalkane, notably (tetrahydrofuran-2, 5-diyl) dimethanamine.
  • Amines are of significant importance to the chemical industry. Synthetic amines are used for solvents, agrochemicals, pharmaceuticals, fabric softeners, flotation agents, corrosion inhibitors, antistatic additives, lubricants, polymers and varnishes.
  • cyclic bi-amnio functional amines are useful as monomers in polymer synthesis and as intermediates as well.
  • These bi-amnio functional materials can be derived from petroleum resources or renewable source-based alternatives.
  • PCT international patent publication no. WO 2015175528 and PCT international patent publication no. WO 2015001061 disclose methods for preparing (tetrahydrofuran-2, 5-diyl) dimethanamine (hereinafter THFDA) from 5-halomethylfurfural.
  • THFDA tetrahydrofuran-2, 5-diyl dimethanamine
  • PCT international patent publication no. WO 2016004867 discloses THFDA could also be obtained from 2, 5-diformylfuran.
  • these methods involve the use of hydrogen and metal catalyst, and usually take multiple reaction steps so as to obtain the desired product.
  • the present invention relates to a process for producing a heterocycloalkane substituted with at least one aminomethyl functional group.
  • the process comprises a step of contacting ammonia with a heterocycloalkane substituted with at least one halomethyl functional group.
  • the process of the present invention does not require involvement of hydrogen or metal catalysts.
  • the present invention also relates to a composition which comprises a heterocycloalkane substituted with at least one halomethyl functional group, and ammonia.
  • any particular upper concentration can be associated with any particular lower concentration.
  • hydrocarbon group refers to a group which contains carbon and hydrogen bonds.
  • a hydrocarbon group may be linear, branched, or cyclic, and may contain a heteroatom such as oxygen, nitrogen, sulfur, halogen, etc.
  • alkyl means a saturated hydrocarbon radical, which may be straight, branched or cyclic, such as, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, t-butyl, pentyl, n-hexyl, cyclohexyl.
  • alkenyl as a group or part of a group denotes an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched.
  • the group may contain a plurality of double bonds in the normal chain and the orientation about each is independently E or Z.
  • Exemplary alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and nonenyl.
  • the group may be a terminal group or a bridging group.
  • aryl refers to a monovalent aromatic hydrocarbon group, including bridged ring and/or fused ring systems, containing at least one aromatic ring. Examples of aryl groups include phenyl, naphthyl and the like.
  • arylalkyl or the term “aralkyl” refers to alkyl substituted with an aryl.
  • arylalkoxy refers to an alkoxy substituted with aryl.
  • cyclic group means a closed ring hydrocarbon group that is classified as an alicyclic group, aromatic group, or heterocyclic group.
  • alicyclic group means a cyclic hydrocarbon group having properties resembling those of aliphatic groups.
  • cycloalkyl as used herein means cycloalkyl groups containing from 3 to 8 carbon atoms, such as for example cyclohexyl.
  • Heterocyclic may also mean a heterocyclic group fused with a benzene-ring wherein the fused rings contain carbon atoms together with 1 or 2 heteroatom’s which are selected from N, O and S.
  • heterocycloalkane is a saturated heterocycle formally derived from a cycloalkane by replacing one or more carbon atoms with a heteroatom.
  • the present invention relates to a process for producing heterocycloalkane substituted with at least one aminomethyl functional group, the process comprising a step of contacting ammonia with a heterocycloalkane substituted with at least one halomethyl functional group.
  • the heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane compound in which at least one hydrogen atom linked with carbon atom of heterocycloalkane ring is substituted with aminomethyl functional group.
  • the heterocycloalkane substituted with at least one halomethyl functional group is a heterocycloalkane compound in which at least one hydrogen atom linked with carbon atom of a heterocycloalkane ring is substituted with halomethyl functional group.
  • the heterocycloalkane substituted with at least one aminomethyl functional group or the heterocycloalkane substituted with at least one halomethyl functional group can comprise a five, six, seven or eight membered heterocycloalkane ring, preferably a five or six membered heterocycloalkane ring and most preferably five membered heterocycloalkane ring.
  • the heterocycloalkane ring may be oxirane, oxetane, tetrahydrofurane, oxane, dioxane, oxepane, oxocane, aziridine, azetidine, azolidine, azinane, azepane, azocane, thiirane, thiirene, thietane, thiolane, thiane, thiepane or thiocane.
  • the heterocycloalkane ring is chosen from the group consisting of tetrahydrofurane, oxane, dioxane, azolidine and thiolane. More preferably, the heterocycloalkane ring is tetrahydrofurane, oxane or dioxane.
  • the heteroatom comprised in the heterocycloalkane ring may notably be one or more selected from N, O and S.
  • the number of heteroatoms contained in the heterocycloalkane may be from 1 to 3.
  • heterocycloalkane ring of the heterocycloalkane substituted with at least one aminomethyl functional group, or heterocycloalkane ring of the heterocycloalkane substituted with at least one halomethyl functional group may be substituted by an additional functional group.
  • the additional functional group may be chosen from the group consisting of halogen, alkyl, aryl, alkenyl and alkoxy functional group. Said alkyl, aryl, alkenyl or alkoxy functional group may notably comprise 1 to 10 carbon atoms.
  • the halogen comprised in the heterocycloalkane substituted with at least one halomethyl functional group may be fluorine, chlorine, bromine, iodine. Among these, iodine is preferred.
  • heterocycloalkane substituted with at least one halomethyl functional group examples include (tetrahydrofuran-2, 5-diyl) dimethaniodide, 2, 6-bis (iodomethyl) tetrahydro-2H-pyran, 2, 7-bis (iodomethyl) oxepane, 2, 6- bis (iodomethyl) -1, 4-dioxane, 2, 5-bis (iodomethyl) tetrahydrothiophene and 2, 6-bis (iodomethyl) tetrahydro-2H-thiopyran.
  • the heterocycloalkane substituted with at least one halomethyl functional group is (tetrahydrofuran-2, 5-diyl) dimethaniodide.
  • the heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane substituted with only one halomethyl functional group.
  • the heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane substituted with two halomethyl functional groups.
  • the heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane substituted with two halomethyl functional groups.
  • heterocycloalkane substituted with at least one aminomethyl functional group examples include (tetrahydrofuran-2, 5-diyl) dimethanamine, (tetrahydro-2H-pyran-2, 6-diyl) dimethanamine, oxepane-2, 7-diyldimethanamine, (1, 4-dioxane-2, 6-diyl) dimethanamine, (tetrahydrothiophene-2, 5-diyl) dimethanamine and (tetrahydro-2H-thiopyran-2, 6-diyl) dimethanamine.
  • the heterocycloalkane substituted with at least one aminomethyl functional group is (tetrahydrofuran-2, 5-diyl) dimethanamine.
  • ammonia can be in the form of gas or liquid. Preference may be given to using liquid ammonia in some embodiments.
  • the reaction according to the invention may be performed in the absence or in the presence of a solvent.
  • the solvent may be protic, aprotic or a combination of protic and aprotic solvents.
  • suitable solvents include water, toluene, octane, xylene, benzene, n-butanol, and acetonitrile.
  • the solvent is a non-polar, aprotic solvent, such as toluene.
  • Preferred solvent is water.
  • concentration of the heterocycloalkane substituted with at least one halomethyl functional group in liquid ammonia may be comprised from 0.002g/ml to 0.400g/ml and more preferably from 0.01g/ml to 0.06g/ml when the reaction is performed in the absence of solvent.
  • Reaction temperature may be from -60°C to -10°C.
  • Reaction time may be from 1 hour to 48 hours.
  • a substance which has the function of activating ammonia can be added in the reaction mixture.
  • the substance can be an alkaline substance other than ammonia.
  • alkaline substance refers to any substance falls into the Arrhenius definition, definition or Lewis definition.
  • alkaline substance falls into Arrhenius definition is a substance that gives the OH - when dissolved in H 2 O, such as alkali metal hydroxide: lithium hydroxide (LiOH) , sodium hydroxide (NaOH) , potassium hydroxide (KOH) , rubidium hydroxide (RbOH) , caesium hydroxide (CsOH) .
  • alkali metal hydroxide lithium hydroxide (LiOH) , sodium hydroxide (NaOH) , potassium hydroxide (KOH) , rubidium hydroxide (RbOH) , caesium hydroxide (CsOH) .
  • Alkaline substance falls into definition is a substance that can accept an H + ion from an acid, such as sodium carbonate (Na 2 CO 3 ) , sodium bicarbonate (NaHCO 3 ) , potassium carbonate (K 2 CO 3 ) , potassium bicarbonate (KHCO 3 ) , sodium methoxide (CH 3 ONa) , potassium methoxide (CH 3 OK) , sodium ethoxide (CH 3 CH 2 ONa) , potassium ethoxide (CH 3 CH 2 OK) , sodium tertbutoxide ( (CH 3 ) 3 CONa) , sodium amide (NaNH 2 ) , potassium tert-butoxide ( (CH 3 ) 3 COK) .
  • Alkaline substance falls into Lewis definition is a substance that can donate a pair of nonbonding electrons, such as pyridine or Et 3 N.
  • the alkaline substance other than ammonia may be one or more selected from sodium methoxide (CH 3 ONa) , potassium methoxide (CH 3 OK) , sodium ethoxide (CH 3 CH 2 ONa) , potassium ethoxide (CH 3 CH 2 OK) , sodium tertbutoxide ( (CH 3 ) 3 CONa) , sodium amide (NaNH 2 ) orpotassium tert-butoxide ( (CH 3 ) 3 COK) .
  • the heterocycloalkane substituted with at least one halomethyl functional group is contacted with ammonia in the presence of an alkaline substance other than ammonia.
  • the heterocycloalkane substituted with at least one halomethyl functional group is contacted with ammonia in the absence of an alkaline substance other than ammonia.
  • the reaction may be conducted in any conventional equipment suitable to effect production of heterocycloalkane substituted with at least one aminomethyl functional.
  • Suitable equipment can particularly be an autoclave.
  • Ammonia gas is charged under pressure from a cylinder to an autoclave which is cooled to a temperature, under which ammonia becomes liquid ammonia.
  • the heterocycloalkane substituted with at least one halomethyl functional group is added into the autoclave.
  • the autoclave is then sealed up and the reaction is performed under temperature and reaction time abovementioned to obtain the desired product.
  • the present invention concerns a composition
  • a composition comprising a heterocycloalkane substituted with at least one halomethyl functional group, and ammonia.
  • the present invention also concerns a composition
  • a composition comprising a heterocycloalkane substituted with at least one halomethyl functional group, ammonia and a substance having the function of activating ammonia.
  • the preparation method can refer to Tetrahedron, 1991 (47) : 3155-3170.

Abstract

Provided is a one-step amination reaction for producing an aminomethyl substituted heterocycloalkane, notably (tetrahydrofuran-2, 5-diyl) dimethanamine.

Description

Process for Preparing an Aminomethyl Substituted Heterocycloalkane
The present invention relates to a one-step amination reaction for producing an aminomethyl substituted heterocycloalkane, notably (tetrahydrofuran-2, 5-diyl) dimethanamine.
BACKROUND
Amines are of significant importance to the chemical industry. Synthetic amines are used for solvents, agrochemicals, pharmaceuticals, fabric softeners, flotation agents, corrosion inhibitors, antistatic additives, lubricants, polymers and varnishes.
Among amines, cyclic bi-amnio functional amines are useful as monomers in polymer synthesis and as intermediates as well. These bi-amnio functional materials can be derived from petroleum resources or renewable source-based alternatives.
For example, PCT international patent publication no. WO 2015175528 and PCT international patent publication no. WO 2015001061 disclose methods for preparing (tetrahydrofuran-2, 5-diyl) dimethanamine (hereinafter THFDA) from 5-halomethylfurfural. PCT international patent publication no. WO 2016004867 discloses THFDA could also be obtained from 2, 5-diformylfuran. However, these methods involve the use of hydrogen and metal catalyst, and usually take multiple reaction steps so as to obtain the desired product.
J. Org. Chem 2002, 67, 1692-1695 reports the synthesis of medium-sized cyclic ether diamines. J. Am. Chem. Soc, 1995, 77, 995-997 reports THFDA could be produced from 2, 5-Bis- (aminomethyl) -tetrahydrofuran. Nevertheless, the starting materials used in the reported process are not commercially available, and therefore, the processes are difficult to be industrialized.
SUMMARY OF INVENTION
It is an objective of the present invention to provide a one-step amination reaction for producing an aminomethyl substituted heterocycloalkane, notably (tetrahydrofuran-2, 5-diyl) dimethanamine. Therefore, the process is simple and cost efficient.
In one aspect, the present invention relates to a process for producing a heterocycloalkane substituted with at least one aminomethyl functional group.  The process comprises a step of contacting ammonia with a heterocycloalkane substituted with at least one halomethyl functional group.
Notably, the process of the present invention does not require involvement of hydrogen or metal catalysts. Thus, it is also an objective of the present invention to provide a reaction for producing an aminomethyl substituted heterocycloalkane under mild reaction condition.
The present invention also relates to a composition which comprises a heterocycloalkane substituted with at least one halomethyl functional group, and ammonia.
DEFINITIONS
For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are collected here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.
The articles “a” , “an” and “the” are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article.
The term “and/or” includes the meanings “and” , “or” and also all the other possible combinations of the elements connected to this term.
Throughout the description, including the claims, the term "comprising one" should be understood as being synonymous with the term "comprising at least one" , unless otherwise specified, and "between" should be understood as being inclusive of the limits.
It should be noted that in specifying any range of concentration, any particular upper concentration can be associated with any particular lower concentration.
It is specified that, in the continuation of the description, unless otherwise indicated, the values at the limits are included in the ranges of values which are given.
As used herein, the term "hydrocarbon group" refers to a group which contains carbon and hydrogen bonds. A hydrocarbon group may be linear, branched, or cyclic, and may contain a heteroatom such as oxygen, nitrogen, sulfur, halogen, etc.
As used herein, the term "alkyl" means a saturated hydrocarbon radical, which may be straight, branched or cyclic, such as, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, t-butyl, pentyl, n-hexyl, cyclohexyl.
As used herein, the term "alkenyl" as a group or part of a group denotes an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched. The group may contain a plurality of double bonds in the normal chain and the orientation about each is independently E or Z. Exemplary alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and nonenyl. The group may be a terminal group or a bridging group.
As used herein, the term "aryl" refers to a monovalent aromatic hydrocarbon group, including bridged ring and/or fused ring systems, containing at least one aromatic ring. Examples of aryl groups include phenyl, naphthyl and the like. The term "arylalkyl" or the term "aralkyl" refers to alkyl substituted with an aryl. The term "arylalkoxy" refers to an alkoxy substituted with aryl.
As used herein, the term "cyclic group" means a closed ring hydrocarbon group that is classified as an alicyclic group, aromatic group, or heterocyclic group. The term "alicyclic group" means a cyclic hydrocarbon group having properties resembling those of aliphatic groups.
As used herein, the term "cycloalkyl" as used herein means cycloalkyl groups containing from 3 to 8 carbon atoms, such as for example cyclohexyl.
"Heterocyclic" may also mean a heterocyclic group fused with a benzene-ring wherein the fused rings contain carbon atoms together with 1 or 2 heteroatom’s which are selected from N, O and S.
As used herein, heterocycloalkane is a saturated heterocycle formally derived from a cycloalkane by replacing one or more carbon atoms with a heteroatom.
As used herein, the terminology " (Cn-Cm) " in reference to an organic group, wherein n and m are each integers, indicates that the group may contain from n carbon atoms to m carbon atoms per group.
DETAILED DESCRIPTION
In one aspect, the present invention relates to a process for producing heterocycloalkane substituted with at least one aminomethyl functional group, the process comprising a step of contacting ammonia with a heterocycloalkane substituted with at least one halomethyl functional group.
The heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane compound in which at least one hydrogen atom linked with carbon atom of heterocycloalkane ring is substituted with aminomethyl functional group.
The heterocycloalkane substituted with at least one halomethyl functional group is a heterocycloalkane compound in which at least one hydrogen atom linked with carbon atom of a heterocycloalkane ring is substituted with halomethyl functional group.
The heterocycloalkane substituted with at least one aminomethyl functional group or the heterocycloalkane substituted with at least one halomethyl functional group can comprise a five, six, seven or eight membered heterocycloalkane ring, preferably a five or six membered heterocycloalkane ring and most preferably five membered heterocycloalkane ring.
The heterocycloalkane ring may be oxirane, oxetane, tetrahydrofurane, oxane, dioxane, oxepane, oxocane, aziridine, azetidine, azolidine, azinane, azepane, azocane, thiirane, thiirene, thietane, thiolane, thiane, thiepane or thiocane. Preferably, the heterocycloalkane ring is chosen from the group consisting of tetrahydrofurane, oxane, dioxane, azolidine and thiolane. More preferably, the heterocycloalkane ring is tetrahydrofurane, oxane or dioxane.
The heteroatom comprised in the heterocycloalkane ring may notably be one or more selected from N, O and S. The number of heteroatoms contained in the heterocycloalkane may be from 1 to 3.
It should be understood that heterocycloalkane ring of the heterocycloalkane substituted with at least one aminomethyl functional group, or heterocycloalkane ring of the heterocycloalkane substituted with at least one halomethyl functional group, may be substituted by an additional functional group. Notably, the additional functional group may be chosen from the group consisting of halogen, alkyl, aryl, alkenyl and alkoxy functional group. Said alkyl, aryl, alkenyl or alkoxy functional group may notably comprise 1 to 10 carbon atoms.
The halogen comprised in the heterocycloalkane substituted with at least one halomethyl functional group may be fluorine, chlorine, bromine, iodine. Among these, iodine is preferred.
Examples of the heterocycloalkane substituted with at least one halomethyl functional group are (tetrahydrofuran-2, 5-diyl) dimethaniodide, 2, 6-bis (iodomethyl) tetrahydro-2H-pyran, 2, 7-bis (iodomethyl) oxepane, 2, 6- bis (iodomethyl) -1, 4-dioxane, 2, 5-bis (iodomethyl) tetrahydrothiophene and 2, 6-bis (iodomethyl) tetrahydro-2H-thiopyran.
Preferably, the heterocycloalkane substituted with at least one halomethyl functional group is (tetrahydrofuran-2, 5-diyl) dimethaniodide.
In some embodiments, the heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane substituted with only one halomethyl functional group.
In some embodiments, the heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane substituted with two halomethyl functional groups.
Preferably, the heterocycloalkane substituted with at least one aminomethyl functional group is a heterocycloalkane substituted with two halomethyl functional groups.
Examples of the heterocycloalkane substituted with at least one aminomethyl functional group are (tetrahydrofuran-2, 5-diyl) dimethanamine, (tetrahydro-2H-pyran-2, 6-diyl) dimethanamine, oxepane-2, 7-diyldimethanamine, (1, 4-dioxane-2, 6-diyl) dimethanamine, (tetrahydrothiophene-2, 5-diyl) dimethanamine and (tetrahydro-2H-thiopyran-2, 6-diyl) dimethanamine.
Preferably, the heterocycloalkane substituted with at least one aminomethyl functional group is (tetrahydrofuran-2, 5-diyl) dimethanamine.
According to the present invention, ammonia can be in the form of gas or liquid. Preference may be given to using liquid ammonia in some embodiments.
The reaction according to the invention may be performed in the absence or in the presence of a solvent. The solvent may be protic, aprotic or a combination of protic and aprotic solvents. Examples of suitable solvents include water, toluene, octane, xylene, benzene, n-butanol, and acetonitrile. In some embodiments, the solvent is a non-polar, aprotic solvent, such as toluene. Preferred solvent is water.
Advantageously, when liquid ammonia is employed in present process, concentration of the heterocycloalkane substituted with at least one halomethyl functional group in liquid ammonia may be comprised from 0.002g/ml to 0.400g/ml and more preferably from 0.01g/ml to 0.06g/ml when the reaction is performed in the absence of solvent.
Reaction temperature may be from -60℃ to -10℃.
Reaction time may be from 1 hour to 48 hours.
According to the present invention, a substance which has the function of activating ammonia can be added in the reaction mixture. For example, the substance can be an alkaline substance other than ammonia.
As used herein, the "alkaline substance" refers to any substance falls into the Arrhenius definition, 
Figure PCTCN2017104404-appb-000001
definition or Lewis definition.
It should be understood by a skilled person that alkaline substance falls into Arrhenius definition is a substance that gives the OH- when dissolved in H2O, such as alkali metal hydroxide: lithium hydroxide (LiOH) , sodium hydroxide (NaOH) , potassium hydroxide (KOH) , rubidium hydroxide (RbOH) , caesium hydroxide (CsOH) .
Alkaline substance falls into
Figure PCTCN2017104404-appb-000002
definition is a substance that can accept an H+ ion from an acid, such as sodium carbonate (Na2CO3) , sodium bicarbonate (NaHCO3) , potassium carbonate (K2CO3) , potassium bicarbonate (KHCO3) , sodium methoxide (CH3ONa) , potassium methoxide (CH3OK) , sodium ethoxide (CH3CH2ONa) , potassium ethoxide (CH3CH2OK) , sodium tertbutoxide ( (CH3) 3CONa) , sodium amide (NaNH2) , potassium tert-butoxide ( (CH3) 3COK) .
Alkaline substance falls into Lewis definition is a substance that can donate a pair of nonbonding electrons, such as pyridine or Et3N.
Preferably, the alkaline substance other than ammonia may be one or more selected from sodium methoxide (CH3ONa) , potassium methoxide (CH3OK) , sodium ethoxide (CH3CH2ONa) , potassium ethoxide (CH3CH2OK) , sodium tertbutoxide ( (CH3) 3CONa) , sodium amide (NaNH2) orpotassium tert-butoxide ( (CH3) 3COK) .
In some embodiments, the heterocycloalkane substituted with at least one halomethyl functional group is contacted with ammonia in the presence of an alkaline substance other than ammonia.
In some embodiments, the heterocycloalkane substituted with at least one halomethyl functional group is contacted with ammonia in the absence of an alkaline substance other than ammonia.
The reaction may be conducted in any conventional equipment suitable to effect production of heterocycloalkane substituted with at least one aminomethyl functional. Suitable equipment can particularly be an autoclave. For example, Ammonia gas is charged under pressure from a cylinder to an autoclave which is cooled to a temperature, under which ammonia becomes liquid ammonia. The heterocycloalkane substituted with at least one halomethyl functional group is  added into the autoclave. The autoclave is then sealed up and the reaction is performed under temperature and reaction time abovementioned to obtain the desired product.
The present invention concerns a composition comprising a heterocycloalkane substituted with at least one halomethyl functional group, and ammonia.
The present invention also concerns a composition comprising a heterocycloalkane substituted with at least one halomethyl functional group, ammonia and a substance having the function of activating ammonia.
The following examples are included to illustrate embodiments of the invention. Needless to say, the invention is not limited to the described examples.
EXPERIMENTAL PART
EXAMPLE 1: Preparation of (tetrahydrofuran-2, 5-diyl) dimethaniodide
The preparation method can refer to Tetrahedron, 1991 (47) : 3155-3170.
Iodine (55.0 g, 220.0 mmol) and saturated solution of sodium bicarbonate, in water (50 mL) were dissolved in Tetrahydrofuran (THF) (200 mL) and to this methyl tert-butyl ether (MTBE) (100 mL) and hexa-1, 5-diene (8.2 g, 100.0 mmol) were added. The mixture was stirred at 20℃ for 4 h. Then the mixture was concentrated in vacuo. The residue was dissolved in 500 ml of MTBE and washed successively with saturated solution of sodium this sulphate (2*200 mL) and water (1*200 mL) . The organic layer was dried and concentrated in vacuo to give 17.5 g of brown oil. The brown oil was purified by chromatography (PE: EA＝10: 1) to give 10.0 g of (tetrahydrofuran-2, 5-diyl) dimethaniodide.
EXAMPLE 2:
A direct amination synthesis route from (tetrahydrofuran-2, 5-diyl) dimethaniodide with ammonia has been developed. Under specific condition: at -45℃, 0.5g of (tetrahydrofuran-2, 5-diyl) dimethaniodide was added into 15mL of ammonia and react at -45℃ for 8 hours, >80％selectivity of desired product (tetrahydrofuran-2, 5-diyl) dimethanamine was obtained with 12％conversion of (tetrahydrofuran-2, 5-diyl) dimethaniodide as measured by GC.

Claims (13)

  1. A process for producing a heterocycloalkane substituted with at least one aminomethyl functional group, the process comprising a step of contacting ammonia with a heterocycloalkane substituted with at least one halomethyl functional group.
  2. The process according to claim 1, wherein the heterocycloalkane substituted with at least one aminomethyl functional group or the heterocycloalkane substituted with at least one halomethyl functional group comprises a five or six membered heterocycloalkane ring.
  3. The process according to claim 2, wherein the heterocycloalkane ring is chosen from the group consisting of tetrahydrofurane, oxane, dioxane, azolidine and thiolane
  4. The process according to any one of claims 1 or 3, wherein the halogen comprised in the heterocycloalkane substituted with at least one halomethyl functional group is iodine.
  5. The process according to any one of claims 1 to 4, wherein the heterocycloalkane substituted with at least one halomethyl functional group is chosen from the group consisting of (tetrahydrofuran-2, 5-diyl) dimethaniodide, 2, 6-bis (iodomethyl) tetrahydro-2H-pyran, 2, 7-bis (iodomethyl) oxepane, 2, 6-bis (iodomethyl) -1, 4-dioxane, 2, 5-bis (iodomethyl) tetrahydrothiophene and 2, 6-bis (iodomethyl) tetrahydro-2H-thiopyran.
  6. The process according to any one of claims 1 to 5, wherein the heterocycloalkane substituted with at least one aminomethyl functional group is chosen from the group consisting of (tetrahydrofuran-2, 5-diyl) dimethanamine, (tetrahydro-2H-pyran-2, 6-diyl) dimethanamine, oxepane-2, 7-diyldimethanamine, (1, 4-dioxane-2, 6-diyl) dimethanamine, (tetrahydrothiophene-2, 5-diyl) dimethanamine and (tetrahydro-2H-thiopyran-2, 6-diyl) dimethanamine.
  7. The process according to any one of claims 1 to 6, wherein concentration of the heterocycloalkane substituted with at least one halomethyl functional group in liquid ammonia is comprised from 0.01g/ml to 0.06g/ml when the reaction is performed in the absence of solvent.
  8. The process according to any one of claims 1 to 7, wherein reaction temperature is from-60℃ to-10℃.
  9. The process according to any one of claims 1 to 8, wherein the heterocycloalkane substituted with at least one halomethyl functional group is contacted with ammonia in the presence of alkaline substance other than ammonia.
  10. The process according to any one of claims 1 to 8, wherein the heterocycloalkane substituted with at least one halomethyl functional group is contacted with ammonia in the absence of alkaline substance other than ammonia.
  11. The process according to any one of claims 1 to 9, wherein the alkaline substance other than ammonia is chosen from the group consisting of sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tertbutoxide, sodium amide andpotassium tert-butoxide.
  12. A composition comprising a heterocycloalkane substituted with at least one halomethyl functional group, and ammonia.
  13. A composition comprising a heterocycloalkane substituted with at least one halomethyl functional group, ammonia and a substance having the function of activating ammonia.
PCT/CN2017/104404 2017-09-29 2017-09-29 Process for preparing aminomethyl substituted heterocycloalkane WO2019061299A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2017/104404 WO2019061299A1 (en) 2017-09-29 2017-09-29 Process for preparing aminomethyl substituted heterocycloalkane

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2017/104404 WO2019061299A1 (en) 2017-09-29 2017-09-29 Process for preparing aminomethyl substituted heterocycloalkane

Publications (1)

Publication Number Publication Date
WO2019061299A1 true WO2019061299A1 (en) 2019-04-04

Family

ID=65900258

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/104404 WO2019061299A1 (en) 2017-09-29 2017-09-29 Process for preparing aminomethyl substituted heterocycloalkane

Country Status (1)

Country Link
WO (1) WO2019061299A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004256397A (en) * 2003-02-24 2004-09-16 Nippon Soda Co Ltd Method for purifying and producing 2,5-bis(aminomethyl)-1,4-dithiane compound
CN101638399A (en) * 2009-08-27 2010-02-03 黎明化工研究院 Method for preparing 3-ammoniac methyl-3-methyl trimethylene oxide
WO2015175528A1 (en) * 2014-05-12 2015-11-19 Micromidas, Inc. Methods of producing compounds from 5-(halomethyl)furfural
WO2016192563A1 (en) * 2015-05-29 2016-12-08 南京明德新药研发股份有限公司 Janus kinase inhibitor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004256397A (en) * 2003-02-24 2004-09-16 Nippon Soda Co Ltd Method for purifying and producing 2,5-bis(aminomethyl)-1,4-dithiane compound
CN101638399A (en) * 2009-08-27 2010-02-03 黎明化工研究院 Method for preparing 3-ammoniac methyl-3-methyl trimethylene oxide
WO2015175528A1 (en) * 2014-05-12 2015-11-19 Micromidas, Inc. Methods of producing compounds from 5-(halomethyl)furfural
WO2016192563A1 (en) * 2015-05-29 2016-12-08 南京明德新药研发股份有限公司 Janus kinase inhibitor

Similar Documents

Publication Publication Date Title
EP3686205B1 (en) Method for producing alkali metal sulfate salt
US2812333A (en) Process for the preparation of 1-(2-hydroxyethyl) imidazolidine-2
JP5709740B2 (en) Process for producing urethanes comprising mono- and difunctional aromatic amines
RU2013133653A (en) METHOD FOR PRODUCING FORMIC ACID AS A RESULT OF INTERACTION OF CARBON DIOXIDE WITH HYDROGEN
JP2017501123A (en) Mono- and dialkyl ethers of furan-2,5-dimethanol and (tetrahydrofuran-2,5-diyl) dimethanol and their amphiphilic derivatives
CN111777496B (en) Preparation method of isolated hydrofluoroether
KR20180113970A (en) Process for producing aryl-substituted para-phenylenediamine-based material
RU2012150739A (en) SYNTHESIS OF ALKYLCYCLOPENTADIENE COMPOUNDS
Zhang et al. Determination of pKa values of fluoroalkanesulfonamides and investigation of their nucleophilicity
WO2019061299A1 (en) Process for preparing aminomethyl substituted heterocycloalkane
EP3008049A1 (en) Process for the production of furanic compounds comprising at least one amine function
WO2015094965A1 (en) Sulfonates of furan-2,5-dimethanol and (tetrahydrofuran-2,5-diyl)dimethanol and derivatives thereof
Maksimowski et al. 3, 3‐Bis (azidomethyl) oxetane (BAMO) Synthesis via Pentaerythritol Tosyl Derivates
Liu et al. Ni and Fe catalyzed cascade radical reactions of oxime esters with diselenides
EP2308862B1 (en) Manufacturing method for fluoropropylene carbonate
US2751414A (en) Perhalocarbon compounds and method of preparing them
CN103922945B (en) Method for synthesizing bis(2-dialkyl aminoethyl)ether
KR102364123B1 (en) Method for producing a sulfonic acid group-containing monomer
WO2020148421A1 (en) Method for the preparation of thiocarbonates
US3134816A (en) Preparation of secondary fluoroalkyl amines
JPWO2012172893A1 (en) Method for producing hexafluoroacetone or hydrate thereof
WO2011097490A1 (en) Method of producing polyalkylated oligoalkylenepolyamines
US3156701A (en) Production of oxacycloalkanes from alkylene halohydrins
EP2998283A1 (en) 1,2-bis(2,2-difluoroethoxy) ethane and manufacturing method thereof
JPH07165750A (en) Trifluoropropylene carbonate and its production

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17926538

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17926538

Country of ref document: EP

Kind code of ref document: A1