Process for preparing phosphorous containing diols or diol derivatives

Abstract

Process for preparing a compound according to formula (I) comprising reacting a compound according to formula (II) with a compound according to formula (III) at a temperature in a range from 50 to 105 °C, wherein R1 is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6C10)-haloaryl, (C7-C10)-aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl, preferably (C1-C8)-alkyl or hydrogen, R2 is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6C10)-aryl, (C6C10)-haloaryl, (C7-C10)-aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl, R3 and R4 are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3 and R4 form together an epoxide group or an ethylene carbonate group, X is oxygen or sulphur, and n is 0 or 1.

Description

[0001] Process for Preparing Phosphorous Containing Diols or Diol Derivatives

[0002] Technical Field of the Invention

[0003] The present invention relates to a process for preparing phosphorus-comprising diols or diol derivatives according to formula (I) defined below, and in particular to phosphorus- comprising diols or diol derivatives used in and suitable for the preparation of glufosinate and / or glufosinate salts. The present invention further relates to certain mixtures particularly suitable for preparing the phosphorus-comprising diols or diol derivatives according to formula (I) defined below.

[0004] Background of the Invention

[0005] The herbicide glufosinate is a non-selective, foliarly applied herbicide considered to be one of the safest herbicides from a toxicological or environmental standpoint. Current commercial chemical synthesis methods for glufosinate yield a racemic mixture of L- and D-glufosinate (Duke et al. 2010 Toxins 2:1943-1962). However, L-glufosinate (also known as phosphinothricin or (S)-2-amino-4-(hydroxy(methyl)phosphonoyl)butanoic acid) is much more potent than D-glufosinate (Ruhland et al. (2002) Environ. Biosafety Res. 1:29-37). Therefore, methods are needed to produce only or primarily the active, L-glufosinate form. Previously, cost effective methods to generate pure L-glufosinate, or a mixture of D- and L-glufosinate enriched for L-glufosinate, have not been available. Therefore, efficient reactions have been developed leading to L-glufosinate, such as proposed in WO 2017 / 151573 Al. This reaction route implements 2-oxo-4- (hydroxy(methyl)phosphinoyl)butyric acid (PPO) as intermediate species. Hence, novel synthesis routes to PPO have been further investigated. Such novel synthesis routes may use intermediates on the basis of phosphorus comprising diols or derivatives thereof.

[0006] Summary of the Invention

[0007] Hence, it is an object of the present invention to provide an efficient process for preparing a diol or a diol derivative. It is in particular an object of the present invention to provide a process for preparing a diol or a diol derivative suitable for and / or used in the preparation of L-glufosinate.

[0008] It has been surprisingly found that above-mentioned problem can be solved by process for preparing a compound according to formula (I) comprising reacting a compound according to formula (II)

[0009] X t R1P11-H

[0010] (O)nR2(H) with a compound according to formula (I II) at a temperature in a range from 50 to 105 ° C, wherein

[0011] R1is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl,

[0012] R2is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6C10)-aryl, (C6C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl,

[0013] R3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group,

[0014] X is oxygen or sulphur, and n is 0 or 1.

[0015] It has been further surprisingly found that above-mentioned object can be achieved by a mixture selected from the group consisting of mixtures comprising one or more compounds according to formula (IV) and a compound according to formula (I II), mixtures comprising one or more compounds according to formula (IV) and a compound according to formula (II), mixtures comprising a compound according to formula (I II) and a compound according to compound (II), wherein the compounds according to formulae (II) and (II I) have the structures as defined above.

[0016] Finally, it has been surprisingly found that above-mentioned object is achieved by the use of a compound according to formula (I) wherein

[0017] R1is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10) - haloa ral kyl , (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl, preferably (C C8)-alkyl or hydrogen,

[0018] R2is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6C10)-aryl, (C6C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10) - haloa ral kyl , (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl, and

[0019] R3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group,

[0020] X is oxygen or sulphur, preferably is oxygen, and n is 0 or 1, for preparing glufosinate and / or glufosinate salts, more particularly glufosinate, glufosinate-sodium or glufosinate-ammonium, more preferably for preparing L-glufosinate and / or L-glufosinate salts, more particularly L-glufosinate, L-glufosinate-sodium or L- glufosinate-ammonium.

[0021] Definitions

[0022] The term “ (C^Cj-alky / ' as used herein denotes the abbreviated notation for an alkyl radical having 1 to 4 carbon atoms, therefore encompassing the radicals methyl, ethyl, 1-propyl, 2- propyl, 1-butyl, 2-butyl, 2-methylpropyl or tert-butyl. Correspondingly, general alkyl radicals with a greater stated range of C atoms, as for example “ (C^C^-alky / ' , also encompass straight-chain or branched alkyl radicals having a greater number of C atoms, i.e., according to example, the alkyl radicals also having 5 and 6 C atoms.

[0023] The term “ (C--C4)-a / kox as used herein denotes the abbreviated notation for an alkoxy radical having 1 to 4 carbon atoms, therefore encompassing the radicals methoxy, ethoxy, 1- propoxy, 2-propoxy, 1-butoxy, 2-butoxy, 2-methylpropoxy or tert-butoxy. Correspondingly, general alkyl radicals with a greater stated range of C atoms, as for example “ (Cg-Cg)- a / kox , also encompass straight-chain or branched alkoxy radicals having a greater number of C atoms, i.e., according to example, the alkoxy radicals also having 5 and 6 C atoms.

[0024] The term “ (Cg-C^-acy / ox as used herein denotes the abbreviated notation for acyloxy radical having 1 to 4 carbon atoms, therefore encompassing the radicals formyloxy, acetyloxy, 1-propionyloxy, or 2-propionyloxy. Correspondingly, general acyloxy radicals with a greater stated range of C atoms, as for example “ (C^Cg-acy / ox , also encompass straight-chain or branched alkyl radicals having a greater number of C atoms, i.e., according to example, the acyloxyradicals also having 5 and 6 C atoms.

[0025] The term “halogen” as used herein denotes a member of the group consisting of fluorine, chlorine, bromine and iodine.

[0026] The terms “ haloalkyl' , “ ha / oaryi' , “ ha / oara / kyi' and “ halocycloalkyl' as used herein denote alkyl, aryl, aralkyl and cycloalkyl, respectively, that are partly or wholly substituted by identical or different halogen atoms, preferably from the group of fluorine, chlorine and bromine, more particularly from the group of fluorine and chlorine. Thus, for example, haloalkyl encompasses monohaloalkyl (=monohalogenoalkyl), dihaloal kyl (=d i h a I ogen oa I ky I) , trihaloal kyl (=tri h a I oge n oa I ky I) , or else perhaloa I kyl , such as, for example, CF3, CHF2, CH2F, CF3CF2, CH2FCHCI, CCI3, CHCI2, CH2CH2CI. Corresponding comments apply to the other radicals substituted by halogen.

[0027] The preparation of the compounds according to formula (II) is known to the skilled person and can take place in accordance with processes known from the literature (e.g. U.S. Pat. No. 3,914,345; U.S. Pat. No. 4,474,711; U.S. Pat. No. 4,485,052; U.S. Pat. No. 4,839,105; U.S. Pat. No. 5,128,495).

[0028] The term “portion” as used herein denotes only part of the total amount used in the process of the invention is used in the procedure defined at that particular point.

[0029] As used in this specification and in the appended claims, the singular forms of "a" and "an” also include the respective plurals unless the context clearly dictates otherwise. I n the context of the present invention, the terms ''about' and ''approximately!' denote an interval of accuracy that a person skilled in the art will understand to still ensure the technical effect of the feature in question. The term typically indicates a deviation from the indicated numerical value of ± 20 %, preferably ± 15 %, more preferably ± 10 %, and even more preferably ± 5 %. It is to be understood that the term "comprising' is not limiting. For the purposes of the present invention the term " consisting of' is considered to be a preferred embodiment of the term " comprising of' . If hereinafter a group is defined to comprise at least a certain number of embodiments, this is meant to also encompass a group which preferably consists of these embodiments only. Furthermore, the terms "first' , "second' , " third' or " (a)', " (b)' , " (c)' , " (d)' etc. and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein. In case the terms "first', "second', " third' or " (a)' , " (b)", " (c)", " (d)", " / ", " / / " etc. relate to steps of a method or use or assay there is no time or time interval coherence between the steps, i.e. the steps may be carried out simultaneously or there may be time intervals of seconds, minutes, hours, days, weeks, months or even years between such steps, unless otherwise indicated in the application as set forth herein above or below. It is to be understood that this invention is not limited to the particular methodology, protocols, reagents etc. described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention that will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0030] As used herein the term "does not comprise" or "free of means in the context that the composition of the present invention is free of a specific compound or group of compounds, which may be combined under a collective term, that the composition does not comprise said compound or group of compounds in an amount of more than 0.8 wt.-%, based on the total weight of the composition. Furthermore, it is preferred that the composition according to the present invention does not comprise said compounds or group of compounds in an amount of more than 0.5 wt.-%, preferably the composition does not comprise said compounds or group of compounds at all.

[0031] Detailed Description of the Invention

[0032] As outlined above, the most general embodiment of the present invention relates to a process for preparing a compound according to formula (I) comprising reacting a compound according to formula (II)

[0033] X d11R1-P-H

[0034] (O)nR2(ID with a compound according to formula (III) at a temperature in a range from 50 to 105 ° C, wherein:

[0035] R1is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl,

[0036] R2is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6-C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl,

[0037] R3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group,

[0038] X is oxygen or sulphur, and n is 0 or 1.

[0039] In a preferred embodiment of the process according to the present invention, R1in formulae (I) and (I I) is selected from methyl, ethyl, and n-butyl, and most preferably is methyl.

[0040] In another preferred embodiment of the process according to the present invention, R2in formulae (I) and (I I) is a (C1-C8)-alkyl or hydrogen, more preferably is selected from hydrogen, methyl, ethyl, and n-butyl, and most preferably is selected from hydrogen, ethyl, and n-butyl.

[0041] In another preferred embodiment of the process according to the present invention, R3and R4in formulae (I) and (III) of the step a) of the process according to the present invention are independently from each other acetyloxy, ethoxy, or n-butoxy, or R3and R4form together an ethylene carbonate group. Especially preferred embodiments of the compounds according to formulae (I) and (III) are selected from the compounds according to formulae (I) and (I II), wherein R3is hydroxy and R4is hydroxy, the compounds according to formulae

[0042] (I) and (I II), wherein R3is hydroxy and R4is acetyloxy, the compounds according to formulae

[0043] (I) and (I II), wherein R3is acetyloxy and R4is hydroxy, the compounds according to formulae

[0044] (I) and (I II), wherein both R3and R4are acetyloxy, and the compounds according to formulae

[0045] (I) and (I II), wherein R3and R4form an ethylene carbonate group. Even more especially preferred embodiments of the compounds according to formulae (I) and (III) are selected from the compounds according to formulae (I) and (II I) wherein both R3and R4are acetyloxy, and the compounds according to formulae (I) and (I II) wherein R3and R4form an ethylene carbonate group. Most preferably, the compounds according to formulae (I) and (III) is the compounds according to formulae (I) and (III), wherein R3and R4form an ethylene carbonate group. The respective alkyl chains as used in the radicals R1, R2, R3, and R4may in each case be straight-chain or branched-chain (branched) in the carbon scaffold.

[0046] The process according to the present invention is preferably carried out at a temperature in the range of from 60 to 95 ° C, more preferably in the range from 65 to 90 ° C.

[0047] A preferred embodiment of the present invention relates to the process for preparing a compound according to formula (la)

[0048] (la), wherein a compound according to formula (Ila) is reacted with a compound according to formula (II I) xR4

[0049] H R3

[0050] (II I) wherein

[0051] R1is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6-C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl,

[0052] R2is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6-C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl, and

[0053] R3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group.

[0054] In a preferred embodiment of the process according to the present invention, R1in formulae (I), (la), (I I), and (Ila) is selected from methyl, ethyl, and n-butyl, and most preferably methyl.

[0055] In another preferred embodiment of the process according to the present invention, R2in formulae (I), (la), (I I), and (Ila) is a (C1-C8)-alkyl or hydrogen, more preferably is selected from hydrogen, methyl, ethyl, and n-butyl, and most preferably is selected from hydrogen, ethyl, and n-butyl. In another preferred embodiment of the process according to the present invention, R3and R4in formulae (I), (la), and (III) of the step a) of the process according to the present invention are independently from each other acetyloxy, ethoxy, or n-butoxy, or R3and R4form together an ethylene carbonate group. Especially preferred embodiments of the compounds according to formulae (I), (la), and (III) are selected from the compounds according to formulae (I), (la), and (III), wherein R3is hydroxy and R4is hydroxy, the compounds according to formulae (I), (la), and (III), wherein R3is hydroxy and R4is acetyloxy, the compounds according to formulae (I), (la), and (III), wherein R3is acetyloxy and R4is hydroxy, the compounds according to formulae (I), (la), and (III), wherein both R3and R4are acetyloxy, and the compounds according to formulae (I), (la), and (III), wherein R3and R4form an ethylene carbonate group. Even more especially preferred embodiments of the compounds according to formulae (I), (la), and (III) are selected from the compounds according to formulae (I), (la), and (III) wherein both R3and R4are acetyloxy, and the compounds according to formulae (I), (la), and (III) wherein R3and R4form an ethylene carbonate group. Most preferably, the compounds according to formulae (I), (la), and (III) is the compounds according to formulae (I), (la), and (III), wherein R3and R4form an ethylene carbonate group.

[0056] In an especially preferred embodiment of the process according to the present invention, in the compound according to formula (II) R1is methyl, R2is n-butyl, n is 1 and X is oxygen.

[0057] In an alternatively especially preferred embodiment of the process according to the present invention, in the compound according to formula (II) R1is methyl, R2is hydrogen, n is 1 and X is oxygen.

[0058] Suitable and preferred compounds according to formula (II) include the following: methanephosphonous acid mono(C1-C6)-alkyl esters, monododecyl methanephosphonate, monophenyl methanephosphonate; ethane-phosphonous acid mono(C1-C6)-alkyl esters, monododecyl ethanephosphonate, monophenyl ethanephosphonate; propanephosphonous acid mono(C1-C6)-alkyl esters, monododecyl propanephosphonate, monophenyl propanephosphonate; butanephosphonous acid mono(C1-C6)-alkyl esters, monododecyl butanephosphonate, monophenyl butanephosphonate; phenylphosphonous acid mono(C1- C6)-alkyl esters, monododecyl phenylphosphonate, monophenyl phenylphosphonate; benzylphosphonous acid mono-(C1-C6)-alkyl esters, monododecyl benzylphosphonate, monophenyl benzylphosphonate; methylthio-phosphonous acid mono(C1-C6)-alkyl esters, monododecyl methylthiophosphonate, monophenyl methylthiophosphonate; dimethylphosphine oxide, diethylphosphine oxide, dipropylphosphine oxide, dibutylphosphine oxide, diphenylphosphine oxide, methylphenylphosphine oxide, dibenzylphosphine oxide, dimethylphosphine sulphide, and diphenylphosphine sulphide. Moreover, the process according to the present invention is preferably carried out under conditions in which free radicals are formed.

[0059] Hence, the reaction of the compounds according to formula (II) and (III) or (Ila) and (III) to give the compounds according to formula (I) or (la), respectively, in a process according to the present invention is preferably carried out with the aid of a radical-forming radiation source (such as UV, gamma or X-rays) or in the presence of one or more radical-forming substances.

[0060] Even more preferably, the reaction of process according to the present invention is carried out with aid of a radical-forming radiation source or in the presence of one or more radicalforming substance. An example for the one or more radical-forming substance is 2,2’ - azobis(isobutyronitrile) (AIBN).

[0061] However, preferably, the one or more radical-forming substance comprises, preferably consists of, a peroxide. More preferably the one or more radical-forming substance comprises, preferably consists of, a compound according to formula (IV) wherein

[0062] R5is methyl, ethyl, 2,2-dimethyl propyl or phenyl,

[0063] R6independently at each occurrence is (C1-C10)-alkyl, and

[0064] R7is hydrogen or (C1-C10)-alkyL

[0065] Even more preferably the compound according to formula (IV) is selected from the group consisting of tert-butyl peroxypivalate, tert-amyl peroxypivalate, tert-butyl peroxyneodecanoate, 1,1,3,3-tetramethylbutyl peroxyneodecanoate, tert-butyl peroxy-2- ethylhexanoate, 1,1,3,3-tetramethylbutyl peroxy-2-ethyl hexanoate, tert-amyl peroxyneodecanoate, cumyl peroxyneodecanoate, cumyl peroxyneoheptanoate, and cumyl peroxypivalate.

[0066] Most preferably, in the one or more radical-forming substance according to formula (IV) R6independently from each other is (Cj-C4) -a I kyl and R7is hydrogen or (Cj-Cj-alkyL

[0067] Preferably, in the process according the present inventio, the molar ratio of the total amount of the compound according to formula (II) used to the total amount of the compound according to formula (III) used is in a range from 2:1 to 8:1. Also preferably, in the process according to the present invention, the one or more radicalforming substance is premixed with a portion or the entirety of compound (II), and this mixture is added into the reaction vessel simultaneously with the compound according to formula (III).

[0068] The one or more radical-forming substances according to formula (IV) are preferably selected from the group consisting of tert-butylperoxyneodecanoate, 1, 1,3,3- tetramethylbutyl peroxyneodecanoate, tert-butylperoxy-2-ethyl-hexanoate, 1, 1,3,3- tetramethylbutyl peroxy-2-ethylhexanoate, cumyl peroxyneodecanoate, and mixtures thereof, more preferably in turn 1,1,3,3-tetramethylbutyl peroxyneodecanoate, tert-butyl peroxyneo-decanoate and / or tert-butylperoxy-2-ethylhexanoate.

[0069] The one or more radical-forming substances stated as preferred, in particular, permit a very good reaction regime under mild reaction conditions, more particularly within the temperature range stated as preferred, thereby allowing the desired phosphorus-comprising diols or diol derivatives according to formula (I) and (la) to be obtained in high yields and high purity.

[0070] Preferably, a total of 0.1 to 10 mol-%, more preferably 0.25 to 7 mol-%, even more preferably 0.5 to 7 mol-%, especially preferably 0.5 to 5 mol-%, of one or more radical-forming substances according to formula (IV), based on the total amount of diol or diol derivative according to formula (III) is used in the process according to the present invention.

[0071] The one or more radical-forming substance according to formula (IV), or a mixture of one or more radical-forming substances according to formula (IV), may be mixed together with the diol or diol derivative according to formula (III), and the mixture added, preferably under dosage control, to the initially introduced compound according to formula (II) or (Ila).

[0072] Alternatively, the one or more radical-forming substance or a mixture of one or more radical-forming substances according to formula (IV) may also be mixed with the phosphorus-comprising reactant according to formulae (II) or (Ila) or added, preferably under dosage control, in pure form simultaneously separately alongside the diol or diol derivative according to formula (III).

[0073] The process of the invention can be carried out such that the one or more radical-forming substances according to formula (IV), or a portion of the one or more radical-forming substances according to formula (IV), is premixed with a portion or the entirety of the compound according to formula (III) (“mixture IV+IH”) and this mixture, i.e. “mixture IV+IH”, is added into the reaction vessel. The process of the invention is preferably carried out such that compound according to formula (III) is premixed with a portion of the compound according to formulae (II) or (Ila) (“mixture III +11”), spatially separately therefrom (i.e. in a separate container), a portion of the compound according to formulae (II) or (Ila) is premixed with the one or more radicalforming substance (IV) (“mixture ll + IV”), and these two mixtures, i.e. “mixture lll + H” and “mixture ll + IV”, are added simultaneously into the reaction vessel.

[0074] The process according to the present invention is preferably carried out such that the one or more radical-forming substances according to formula (IV) or a portion of the one or more radical-forming substances according to formula (IV) is or are premixed with a portion or the entirety of the compound according to formulae (II) or (Ila) (“mixture IV+H”), and this mixture, i.e. “mixture IV+H”, is added simultaneously with and separately from the compound according to formula (III) into the reaction vessel.

[0075] The compound according to formula (III) is preferably added into the reaction vessel from a separate container that constitutes a separate construction.

[0076] If the process according to the present invention is carried out in batch mode, and depending on the batch size, the simultaneous adding in each of the above-mentioned procedures lasts preferably for longer than 30 min, more preferably 30 min to 20 h, and most preferably 1 to 12 h.

[0077] The above-defined mixtures “mixture IV+III”, “mixture IV+H”, “mixture lll + ll”, and “mixture ll + IV” are likewise provided by the present invention.

[0078] The present invention consequently also relates to a composition selected from the group consisting of a mixture comprising one or more compounds according to formula (IV) and one or more compounds of the compound (III) formula, a mixture comprising one or more compounds according to formula (IV) and one or more compounds according to formula (II), a mixture comprising one or more compounds according to formula (III) and one or more compounds according to formula (II), wherein such a mixture preferably contains no compound of the above-defined formula (IV) and / or no compound of the abovedefined formula (I), wherein the compounds according to formulae (II), (III) and (IV) each have the structure defined above, preferably in each case a structure defined above as preferred or particularly preferred. Preferably, the radical-forming substance does not comprise a boron-based compound, preferably not a borane, most preferably not triethylborane. Triethylborane causes safety issues under industrial scale production conditions and requires very low temperature due to its high reactivity.

[0079] The present invention preferably relates to a composition selected from the group consisting of a mixture comprising one or more compounds according to formula (IV) and one or more compounds according to formula (III), a mixture comprising one or more compounds according to formula (IV) and one or more compounds according to formula (II), wherein the compounds according to formulae (II), (III) and (IV) each have the structure defined above, preferably in each case a structure defined above as preferred or particularly preferred.

[0080] For the compositions according to the present invention, it is preferably the case that the compounds according to formula (II) are selected from the group of the compounds according to formula (Ila).

[0081] Preferred compositions according to the present invention comprise or consist of one or more radical-forming substances according to formula (IV) selected from the group consisting of tert-butyl peroxypivalate, tert-amyl peroxypivalate, tert-butyl peroxyneodecanoate, 1,1,3,3-tetramethylbutyl peroxyneodecanoate, tert-butylperoxy-2- ethylhexanoate, 1,1,3,3-tetramethylbutyl peroxy-2-ethyl-hexanoate, tert-amyl peroxyneodecanoate, cumyl peroxyneodecanoate, cumyl peroxyneoheptanoate, and cumyl peroxypivalate, and a compound according to formula (III).

[0082] Preferred compositions according to the invention comprise or consist of one or more radical-forming substances according to formula (IV) selected from the group consisting of tert-butyl peroxypivalate, tert-amyl peroxypivalate, tert-butyl peroxyneodecanoate, 1,1,3,3- tetramethylbutyl peroxyneodecanoate, tert-butylperoxy-2-ethylhexanoate, 1,1,3,3- tetramethylbutyl peroxy-2-ethyl-hexanoate, tert-amyl peroxyneodecanoate, cumyl peroxyneodecanoate, cumyl peroxyneo-heptanoate, and cumyl peroxypivalate, and a compound according to formula (II), preferably according to formula (Ila).

[0083] The process of the invention enables the preparation of the phosphorus-comprising diols or diol derivatives according to formulae (I) or (la) under mild reaction conditions, thereby giving the phosphorus-comprising diols or diol derivatives according to formulae (I) or (la) in very good yields. Accordingly, when the process of the invention is implemented, disproportionation of reactants according to formulae (II) or (Ila), for example, is significantly lessened or largely prevented. Moreover, when the process of the invention is implemented, polymerization of the compounds according to formula (III) is significantly lessened or largely prevented.

[0084] It has further been found that by premixing (parts) of the reactants according to formulae (II) and (III) or (Ila) and (III), the polymerization tendency of compounds according to formula (III) can be still further reduced.

[0085] In the context of the process of the invention it is advantageous to use the diols or diol derivatives according to formula (III) in a very high purity. The diols or diol derivatives according to formula (III) are preferably used in a purity of greater than or equal to 90 wt.-%, more preferably of greater than or equal to 92 wt.-%.

[0086] The phosphorus-comprising diols or diol derivatives according to formula (I) or (la) that are formed may be used as starting materials for the synthesis of phosphorus-comprising amino acids such as, for example, glufosinate.

[0087] In order to avoid unwanted secondary reactions and hence to achieve high yields, moreover, it is advantageous to use the phosphorus-comprising reactant according to formulae (II) or (Ila) in a molar excess, relative to the compound according to formula (III).

[0088] In the process according to the present invention, the molar ratio of the total amount of the phosphorus-comprising reactant according to formulae (II) or (Ila) used to the total amount of the compound according to formula (III) used is preferably in the range from 3:2 to 8:1, more preferably in the range from 2:1 to 6:1, more preferably still in the range from 5:2 to 5:1, very preferably in the range from 2.8:1 to 4.0:1.

[0089] The process of the invention can be carried out either in batch mode or in continuous mode (i.e. continuous operating regime).

[0090] The process of the invention is carried out preferably with inertizing, more preferably in an inert gas atmosphere. Preferred inert gases in this case are nitrogen and argon.

[0091] It is further possible to carry out the process of the invention under superatmospheric pressure or under reduced pressure.

[0092] The process of the invention can be carried out in a diluent.

[0093] As diluents it is possible in principle to use a variety of organic solvents, preferably toluene, xylene, chlorobenzene, dichlorobenzene, dimethylformamide (DMF), dimethylacetamide, N- methyl-2-pyrrolidone (NMP), or mixtures of these organic solvents. The process of the invention is preferably carried out without such solvents. It may, however, be advantageous to carry out the process of the invention in reaction product according to formulae (I) or (la), already formed beforehand, as diluent.

[0094] It may be advantageous to carry out the process of the invention in the reactant according to formulae (II) or (Ila) as diluent, in which case preferably a portion of the reactant according to formulae (II) or (Ila) is introduced as an initial charge to the reaction vessel or reactor.

[0095] Particularly in the case of continuous mode, it is advantageous to carry out the process of the invention in reaction product according to formulae (I) or (la), already formed beforehand, or in a mixture of reaction product according to formulae (I) or (la) and reactant according to formulae (II) or (Ila), as diluent.

[0096] The yields according to the process of the invention amount regularly to 90-98%, based on the component according to formula (III), and regularly to 88-96%, based on the component according to formula (II) or (Ila).

[0097] The purity of the products after purification, for example after disti I lative removal of the excess of component according to formulae (II) or (Ila), amounts regularly to 90% to 96%. The recovered excess of the starting compound according to formula (II) can be used subsequently without further purification in the same reaction again.

[0098] If the compound according to formulae (I) or (la) are not present as free diols, but rather as diol derivatives, i.e. if in formulae (I) or (la) R3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group, the compound according to formula (I) is preferably subsequently to the preparation process treated with an acid, wherein a compound according to formula (V) is formed:

[0099] Most preferably, if the compound according to formula (la) is not present as a free diol, but rather as a diol derivative, i.e. if in formula (I) R3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group, the compound according to formula (la) is treated with an acid, wherein a compound according to formula (Va) is formed:

[0100] Preferably, the acid treatment is carried out in an aqueous medium.

[0101] Also preferably, the acid treatment is carried out using sulfuric acid or hydrochloric acid, preferably hydrochloric acid.

[0102] The acid treatment is preferably carried out at a temperature of 80 to 100 ° C. Also preferably, the acid treatment is carried out at a pressure in the range of from 1.1 to 10 bar.

[0103] The present invention further relates to the use of the diols or diol derivatives according to formulae (I), (la), (V), and (Va), preferably of the diol according to formula (Va), in the preparation process to yield L-glufosinate. Such a preparation process may include oxidation of the diol to PPO and further reaction according to the process as described in WO 2017 / 151572 Al.

[0104] Hence, the diols and diol derivatives according to formulae (I), (la), (V), and (Va), preferably of the diol according to formula (Va), are in particular suitable for being used in a process for preparing L-glufosinate. Such a preparation process may include oxidation of the diol to PPO and further reaction according to the process as described in WO 2017 / 151572 Al.

[0105] Examples

[0106] Example IE1

[0107] To 6 g methylphosphinic acid butyl ester (MPE) was added 5 ml toluene under stirring at room temperature followed by 20 mg 2,2’-azobis(isobutyronitrile) (AIBN). The reaction mixture was heated to 65 ° C. A solution of 2.0 g 3,4-diacetoxy-l-butene in 5 mL toluene was added to the reaction mixture. The addition was carried out dropwise over 30 min.

[0108] After the addition had been finished, the temperature was increased to 75 ° C and the reaction mixture was stirred for additional 5 h. Toluene was removed under reduced pressure on a rotary evaporator. Excess MPE was distilled off at a pressure below 1 mbar and a temperature above 60 ° C. The distillation sump contained the pure product (3.3 g,

[0109] 92%).XH NMR analysis (400 MHz, Chloroform-d) revealed <5 5.13 - 5.03 (m, 1H), 4.29 - 4.20 (m, 1 H) , 4.11 - 3.91 (m, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 1.99 - 1.58 (m, 6H), 1.47 (d, J = 13.6 Hz, 3H), 1.44 - 1.35 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H).

[0110] Example IE2

[0111] 80 mL of aq. HCI (17% w / w) were added to a mixture of 1 g of starting material as prepared according to I El. The reaction mixture was stirred at 100 ° C for 24 h and concentrated in vacuo yielding 505 mg of product diol.

[0112] JH NMR analysis (400 MHz, Deuterium Oxide) revealed <5 3.74 - 3.68 (m, 1H), 3.64 - 3.56

[0113] (m, 1H), 3.55 - 3.46 (m, 1H), 2.02 - 1.47 (m, 7H). LC-MS found 169.1 (M + H)+.

[0114] Example IE3

[0115] To 49.8 g methylphosphinic acid butyl ester (MPE) was added 50 ml toluene under stirring at room temperature followed by 120 mg 2,2’-azobis(isobutyronitrile) (AIBN). The reaction mixture was heated to 75 ° C. A solution of 11.0 g 4-vinyl-l,3-dioxolan-2-one (vinyl ethylene carbonate, CAS 4427-96-7) in 30 mL toluene was added to the reaction mixture. The addition was carried out dropwise over 60 min. The reaction mixture was stirred at 75° C for an additional 7 h. Excess MPE was distilled off at a pressure below 1 mbar and a temperature above 60 ° C using a thin film evaporator. The distillation sump contained the product and was further purified by column chromatography using Methanol / Dichloromethane (22.0 g, 91%).

[0116] JH NMR analysis (400 MHz, Chloroform-d) revealed <5 4.90 - 4.77 (m, 1H), 4.63 - 4.53 (m, 1H), 4.17 - 4.07 (m, 1H), 4.07 - 3.91 (m, 2H), 2.15 - 1.72 (m, 4H), 1.72 - 1.59 (m, 2H), 1.59 - 1.46 (m, 3H), 1.45 - 1.33 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H).

[0117] Example IE4

[0118] 100 mL of aq. HCI (20% w / w) were added to a mixture of 16.5 g of starting material as prepared according to IE3. The reaction mixture was stirred at 90 ° C for 4 h and concentrated in vacuo yielding the product diol.

[0119] Comparative Example CE1

[0120] To 1 g methylphosphinic acid butyl ester (MPE) was added 840 mg 4-vinyl-l,3-dioxolan-2- one (1.0 eq, vinyl ethylene carbonate, CAS 4427-96-7) under stirring at room temperature. The reaction mixture was cooled to -15 ° C and methanol (5 g) was added. Subsequently 880 pL triethyl borane solution (1 M in hexanes) were added. The reaction was stirred at - 15 ° C for 4 hours. Then it was allowed to warm to room temperature and stirred at this temperature for an additional 44 h. After this period both starting materials were only partially converted to the product. (GC area percentage of product: 16%)

[0121] Inventive Example IE5

[0122] To 5 g methylphosphinic acid butyl ester (MPE) was added 5 ml toluene under stirring at room temperature followed by 18.8 mg tert-butyl peroctoate (CAS: 13467-82-8). The reaction mixture was heated to 75 ° C. Subsequently, 1.1 g 4-vinyl-l,3-dioxolan-2-one (vinyl ethylene carbonate, CAS 4427-96-7) dissolved in 3 mL toluene, was added over 3 h. The reaction was then further stirred at this temperature for 2.5h. After this period, GC showed full conversion of 4-vinyl-l,3-dioxolan-2-one to the desired product.

Claims

Claims1. Process for preparing a compound according to formula (I)comprising reacting a compound according to formula (II)X d11R1-P-H(O)nR2(ID with a compound according to formula (I II)at a temperature in a range from 50 to 105 ° C, wherein:R1is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6-C10)-haloaryl, (C7- C10) -a ra I kyl , (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl, preferably (C1-C8)-alkyl or hydrogen, most preferably methyl,R2is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6-C10)-haloaryl, (C7- C10) -a ra I kyl , (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl, preferably (C1-C8)-alkyl, most preferably hydrogen, ethyl, or n-butyl,R3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group, preferably hydroxy, acetyloxy or form together an ethylene carbonate group, most preferably R3and R4form together an ethylene carbonate group,X is oxygen or sulphur, and n is 0 or 1.

2. The process according to claim 1, wherein thereaction takes place at a temperature in the range of from 60 to 95 ° C, preferably in the range from 65 to 90 ° C.

3. The process according to claims 1 or 2, wherein a compound according to formula (Ila)is reacted with a compound according to formula (III)whereinR1is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6C10)-haloaryl, (C7- C10) -a ra I kyl , (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl, preferably (C1-C8)-alkyl or hydrogen, more preferably methyl, ethyl, or n-butyl, most preferably methyl,R2is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6C10)-aryl, (C6C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl, preferably (Cj-Cg) -al kyl, most preferably hydrogen, ethyl, or n-butyl, andR3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group, preferably R3and R4form together an ethylene carbonate group.

4. The process according to any of the preceding claims 1 to 3, wherein the reaction is carried out with aid of a radical-forming radiation source or in the presence of one or more radical-forming substance.

5. The process according to claim 4, wherein the one or more radical-forming substance comprises a compound according to formula (IV)whereinR5is methyl, ethyl, 2,2-dimethyl propyl or phenyl,R6independently of each other is (C1-C10)-alkyl andR7is hydrogen or (C1-C10)-alkyL6. The process according to claim 5, wherein the compound according to formula (IV) is selected from the group consisting of tert-butyl peroxypivalate, tert-amyl peroxypivalate, tert-butyl peroxyneodecanoate, 1,1,3,3-tetramethylbutyl peroxyneodecanoate, tert-butyl peroxy-2-ethylhexanoate, 1,1,3,3-tetramethylbutyl peroxy-2-ethylhexanoate, tert-amyl peroxyneodecanoate, cumyl peroxyneodecanoate, cumyl peroxyneoheptanoate, and cumyl peroxypivalate.

7. The process according to claim 5, wherein R6independently at each occurrence is (C C4)-alkyl and R7is hydrogen or (Cj-Cj-alkyL8. The process according to any of the preceding claims 1 to 7, wherein the molar ratio of the total amount of the compound according to formula (II) used to the total amount of the compound according to formula (III) used is in a range from 2:1 to 8:1.

9. The process according to any of the preceding claims 4 to 7, wherein the one or more radical-forming substance is premixed with a portion or the entirety of compound (II), and this mixture is added into the reaction vessel simultaneously with the compound according to formula (III).

10. The process according to any of the preceding claims 1 to 9, wherein R1is methyl, R2is n-butyl, n is 1 and X is oxygen, or wherein R1is methyl, R2is hydrogen, n is 1 and X is oxygen.

11. The process according to any of the preceding claims 1 to 10, wherein the compound according to formula (I) is treated with an acid, wherein a compound according to formula (V) is formed:

12. The process according to any of the preceding claims 3 to 10, wherein the compound according to formula (I) is treated with an acid, wherein a compound according to formula (Va) is formed:

13. The process according to any of the preceding claims 11 or 12, wherein the treatment is carried out in an aqueous medium and / or wherein the treatment is carried out usinghydrochloric acid and / or wherein the treatment is carried out at a temperature of 80 to 100 ° C.

14. A composition selected from the group consisting of mixtures comprising one or more compounds according to formula (IV) and a compound according to formula (I II), mixtures comprising one or more compounds according to formula (IV) and a compound according to formula (II), mixtures comprising a compound according to formula (III) and a compound according to compound (II), wherein the compounds according to formulae (II) and (III) have the structures as defined in claim 1 and the compound according to formula (IV) has the structure as defined in claim 5.

15. The use of a compound according to formula (I)whereinR1is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6-C10)-aryl, (C6C10)-haloaryl, (C7-C10) -a ra I kyl , (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl or (C4-C10)-halocycloalkyl, preferably (C1-C8)-alkyl or hydrogen, more preferably methyl, ethyl, or n-butyl, most preferably methyl,R2is hydrogen, (C1-C12)-alkyl, (C1-C12)-haloalkyl, (C6C10)-aryl, (C6C10)-haloaryl, (C7-C10)- aralkyl, (C7-C10)-haloaralkyl, (C4-C10)-cycloalkyl, or (C4-C10)-halocycloalkyl, preferably (C1-C8)-alkyl, and most preferably is selected from hydrogen, ethyl, and n-butyl, andR3and R4are independently from each other (C1-C8)-acyloxy, (C1-C8)-alkoxy or hydroxy, or R3and R4form together an epoxide group or an ethylene carbonate group, preferably R3and R4form together an ethylene carbonate group,X is oxygen or sulphur, preferably is oxygen, and n is 0 or 1, for preparing glufosinate and / or glufosinate salts, more particularly glufosinate, gl uf os i nate-sod i u m or glufosinate-ammonium, more preferably for preparing L-glufosinate and / or L-glufosinate salts, more particularly L-glufosinate, L-glufosinate- sodium or L-glufosinate-ammonium.

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