Novel synthetic access to urea derivatives

Abstract

The present invention pertains to a process for preparing an isocyanate-containing compound comprising the step of reacting a compound of formula (1) (1) with oxalyl chloride.

Description

[0001] Novel Synthetic Access to Urea Derivatives

[0002] Background The invention relates to a process for preparing an isocyanate-containing compound, which can be used for preparing a compound of formula (3)

[0003] (3).

[0004] Urea derivatives are known potential drugs or herbicides. A commonly known industrial synthetic route involves the use of phosgene (WO 2001 / 23368). Phosgene, which is a dangerous gas, re- quires the use of special efforts to ensure a safe production.

[0005] Special dedicated phosgene plants are designed to perform phosgenation. For example, the syn- thesis of lodosulfuron involves phosgenation, which is depicted in the below scheme (conversion of methyl 4-lodo-2-sulfamoylbenzoate to the respective isocyanate, followed by the conversion of the isocyanate to lodosulfuron).

[0006] Due to the dangerous nature of phosgene, this is not an easily accessible technology so that a safer alternative route is being needed.

[0007] Against this background, it is an object of the present invention to provide a safe and / or broadly accessible process for manufacturing isocyanate-containing compound. It is a further object of the present invention to provide a safe and / or broadly accessible starting material for a process for manufacturing urea derivatives such as lodosulfuron. It is a further object of the present invention to provide a cost-efficient process for manufacturing isocyanate-containing compound. It is a further object of the present invention to provide a selective process for manufacturing isocyanate-containing compound.

[0008] Summary

[0009] The present invention provides a process for preparing an isocyanate-containing compound, the process comprising the step of reacting a compound of formula (1)

[0010] (1), wherein

[0011] R1 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, aryl, haloaryl, C3-8-cy- cloalkyl, C3-8-halocycloalkyl, O(CO)-RM, NRMRN, or NH(CO)RM;

[0012] R2 is COO-RP, CO-RP, CONRPRQ, or CN;

[0013] R3 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, aryl, haloaryl, C3-8-cy- cloalkyl, C3-8-halocycloalkyl, O(CO)-RM, NRMRN, or NH(CO)RM, COO-RP, CO-RP, CONRPRQ, or CN;

[0014] RMis C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl;

[0015] RNis H, C1-6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl;

[0016] Rpis C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl;

[0017] RQis H, C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl; with oxalyl chloride.

[0018] Detailed Description

[0019] In the following, the invention will be explained in more detail.

[0020] Within this specification, embodiments have been described in a way that enables a clear and concise specification to be written, but it is intended and will be appreciated that embodiments may be variously combined or separated without departing from the disclosure. For example, it will be appreciated that all preferred features described herein are applicable to all aspects of the disclosure described herein.

[0021] In some example embodiments, the disclosure herein can be construed as excluding any element or process step that does not materially affect the basic and novel characteristics of the composition or process. Additionally, in some embodiments, the disclosure can be construed as excluding any element or process step not specified herein.

[0022] As used herein, the terms “about,” “approximately,” or “generally,” when used to modify a value, indicates that the value can be raised or lowered by 10% and remain within the disclosed aspect, such as 7.5%, such as 5%, such as 4%, such as 3%, such as 2%, such as 1 %, or any ranges or values therebetween. For example, the term “about” in the context of the present invention denotes 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 ±10%, preferably ±5%, more preferably ±2%, and in particular ±1 %.

[0023] Moreover, the term “substantially free of’ when used to describe the amount of substance in a material is not to be limited to entirely or completely free of and may correspond to a lack of any appreciable or detectable amount of the recited substance in the material. Thus, e.g., a material is “substantially free of’ a substance when the amount of the substance in the material is less than the precision of an industry-accepted instrument or test for measuring the amount of the substance in the material. In certain example embodiments, a material may be “substantially free of’ a substance when the amount of the substance in the material is less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1 %, less than 0.5%, or less than 0.1 % by weight of the material. It will be understood that, in certain example embodiments, the compositions described herein may be substantially free of any substance not specifically recited.

[0024] As used in this application and in the claims, the singular forms “a,” “an,” and “the” include the plural forms unless the context clearly dictates otherwise. Additionally, the term “includes” means “comprises.” The methods and compositions of the present disclosure, including components thereof, can comprise, consist of, or consist essentially of the essential elements and limitations of the embodiments described herein, as well as any additional or optional ingredients, components or limitations described herein or otherwise useful in nutritional compositions. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, percentages, and so forth, as used in the specification or claims are to be understood as being modified by the term “about.” Accordingly, unless otherwise indicated, implicitly or explicitly, the numerical parameters set forth are approximations that may depend on the desired properties sought and / or limits of detection under standard test conditions / methods. When directly and explicitly distinguishing embodiments from discussed prior art, the embodiment numbers are not approximates unless the word “about” is recited.

[0025] As used herein, “optional” or “optionally” means that the subsequently described material, event or circumstance may or may not be present or occur, and that the description includes instances where the material, event or circumstance is present or occurs and instances in which it does not. As used herein, “w / w%” and “wt%” means by weight as a percentage of the total weight or relative to another component in the composition.

[0026] Although the disclosure is illustrated and described herein with reference to specific embodiments, the disclosure is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the disclosure.

[0027] The term “alkyl” as used herein denotes in each case a straight-chain or branched saturated hydrocarbon group having usually from 1 to 6 carbon atoms, preferably 1 to 5 or 1 to 4 carbon atoms, more preferably 1 to 3 or 1 to 2 or 1 carbon atoms. Examples of an alkyl group are methyl, ethyl, n- propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1 -methylbutyl, 2-methylbutyl, 3-me- thyl-butyl, 2,2-dimethylpropyl, 1 -ethylpropyl, n-hexyl, 1 ,1 -dimethylpropyl, 1 ,2-dimethylpropyl, 1- methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 , 1-dimethylbutyl, 1 ,2-dimethyl-butyl, 1 ,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1 ,1 ,2-trimethylpropyl, 1 ,2,2-trimethylpropyl, 1-ethyl-1 -methylpropyl, 1-ethyl-2-methylpropyl, and the like.

[0028] The term "haloalkyl" as used herein denotes in each case a straight-chain or branched saturated hydrocarbon group having usually from 1 to 6 carbon atoms, frequently from 1 to 5 or 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms. Preferred haloalkyl moieties are selected from C1-C4-haloalkyl, more preferably from C1-C3- haloalkyl or C1-C2-haloalkyl, in particular from C1-C2-fluoroalkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, and the like. The term “alkoxy” as used herein denotes in each case alkyl (similarly the term “haloalkoxy” denotes a haloalky I) substituents, preferably alkyl substituents (or a haloalky I substituent, respectively), as defined above that are connected to another structural moiety via an oxygen atom (-O-). Exemplary alkoxy groups are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy, tertbutoxy, n-pentoxy, and the like. Exemplary haloalkoxy groups are trifluoromethoxy, 2,2,2-trifluoro- ethoxy, and the like.

[0029] The term “cycloalkyl” as used herein refers to a bi- or monocyclic hydrocarbon that has - in general and if not defined otherwise in the specification - a single point of attachment to the remainder of the molecule, with 3, 4, 5, 6, 7, or 8 ring carbon atoms. In some embodiments, cycloalkyl refers to a monocyclic C3-C8 hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule. Preferably, the term cycloalkyl denotes a saturated monocyclic hydrocarbon. C3-8-cycloalkyl groups may in general be unsubstituted or substituted with - unless specified differently elsewhere in this specification - 1 , 2 or 3 substituents that may be the same of different and are - unless specified differently elsewhere in this specification - selected from the group comprising C1 -6-alkyl, C1-6- alkoxy, halogen, hydroxy, unsubstituted or mono- or di-substituted amino. Exemplary C3-8-cycloal- kyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. The term “halocy- cloalkyl” as used herein refers a cycloalkyl as above defined, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms.

[0030] The term “aryl” as used herein refers to aromatic ring systems (i.e. fulfilling the Huckel rule - having (4n+ir2) electrons, with n being 0 or an integer of preferably 1 to 3) which can be in mono-, bi- or tricyclic form. Examples of such rings include phenyl, naphthyl, or indenyl. Preferred aryl groups are phenyl and naphthyl, phenyl being most preferred. The term “haloaryl” as used herein refers to an aryl as above defined, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms.

[0031] The term “heteroaryl” as used herein refers to an aromatic cyclic ring, wherein at least one carbon atom of the ring atoms is replaced by a heteroatom such as nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, te- trazoly I, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, furazanyl, pyridyl (pyri- dinyl), pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, and pyrrolopyridinyl, in particular triazinyl. The term "substituted" as used herein, means that a hydrogen atom bonded to a designated atom is replaced with a specified substituent, provided that the substitution results in a stable or chemically feasible compound. Unless otherwise indicated, a substituted atom may have one or more substituents and each substituent is independently selected.

[0032] The term "substitutable", when used in reference to a designated atom, means that attached to the atom is a hydrogen, which can be replaced with a suitable substituent.

[0033] When it is referred to certain atoms or moieties being substituted with "one or more" substituents, the term "one or more" is intended to cover at least one substituent, e.g. 1 to 10 substituents, preferably 1 , 2, 3, 4 or 5 substituents, more preferably 1 , 2, or 3 substituents, most preferably 1 or 2 substituents. When neither the term "unsubstituted" nor "substituted" is explicitly mentioned concerning a moiety, said moiety is to be considered as unsubstituted.

[0034] The skilled person is aware that S, SO or SO2 is to be understood as follows:

[0035] A„ AC. A .

[0036] S S o o

[0037] It is to be understand that denotes the bond of the respective moiety to the remainder of the molecule.

[0038] The organic moieties mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members. The prefix Cn-Cm indicates in each case the possible number of carbon atoms in the group.

[0039] The term “(CO)” as used herein denotes a carbonyl moiety (also known as “C=O” or as “CO”) and can be expressed as follows:

[0040] The term “COO” as used herein denotes a carboxyl moiety.

[0041] The term “halogen” denotes in each case fluorine, bromine, chlorine, or iodine.

[0042] It needs 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 also meant to encompass a group which preferably consists of these embodiments only. As aforementioned, the present invention relates to a process for preparing an isocyanate-containing compound, the process comprising the step of reacting a compound of formula (1)

[0043] (1), wherein

[0044] R1 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, aryl, haloaryl, C3-8-car- bocyclo, C3-8-halocarbocyclo, O(CO)-RM, NRMRN, or NH(CO)RM;

[0045] R2 is COO-RP, CO-RP, CONRPRQ, or CN;

[0046] R3 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, aryl, haloaryl, C3-8-car- bocyclo, C3-8-halocarbocyclo, O(CO)-RM, NRMRN, or NH(CO)RM, COO-RP, CO-RP, CONRPRQ, or CN;

[0047] RMis C1-6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-carbocyclo, or C3-8-halocarbocyclo;

[0048] RNis H, C1-6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-carbocyclo, or C3-8-halocarbocyclo;

[0049] Rpis C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-carbocyclo, or C3-8-halocarbocyclo;

[0050] RQis H, C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-carbocyclo, or C3-8-halocarbocyclo; with oxalyl chloride.

[0051] The inventive process provides isocyanate-containing compound in a safe and / or selective manner.

[0052] The respective isocyanate-containing compound is particularly suitable to further react to a urea derivate.

[0053] In the following, particular embodiments of the present invention such as moieties and reaction conditions are described in further details. It is to be understood that each embodiment is relevant on its own as well as in combination with other embodiments.

[0054] In one embodiment, R1 is not H.

[0055] In one embodiment, R1 is halogen, C1 -6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, aryl, haloaryl, C3-8-carbocyclo, C3-8-halocarbocyclo, O(CO)-RM, NRMRN, or NH(CO)RM, preferably halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, aryl, haloaryl, C4-6-carbocyclo, C4- 6-halocarbocyclo, O(CO)-RM, NRMRN, or NH(CO)RM, more preferably Cl, Br, I, C1-3-alkyl, C1-3- haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, phenyl, halophenyl, O(CO)-RM, NRMRN, or NH(CO)RM, still more preferably Cl, Br, I, C1 -3-alkyl, or C1-3-haloalkyl, even more preferably Cl, Br, or I, and in particular I.

[0056] In one embodiment, RMis C1-4-alkyl, C1-4-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6-halo- carbocyclo, preferably C1 -3-alkyl, C1-3-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6-halocar- bocyclo, more preferably C1 -3-alkyl, C1-3-haloalkyl, phenyl, halophenyl, and in particular methyl, trifluoromethyl, or phenyl.

[0057] In one embodiment, RNis H, C1 -4-alkyl, C1-4-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6- halocarbocyclo, preferably H, C1 -3-alkyl, C1-3-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6- halocarbocyclo, more preferably H, C1 -3-alkyl, C1-3-haloalkyl, phenyl, halophenyl, and in particular H, methyl, trifluoromethyl, or phenyl.

[0058] In one embodiment, R2 is COO-(C1-6-alkyl), COO-(C1-6-haloalkyl), COO-aryl, COO-haloaryl, CO- (C1 -6-alkyl), CO-(C1-6-haloalkyl), CO-aryl, or CO-haloaryl, preferably COO-(C1 -3-alkyl), COO-(C1- 3-haloalkyl), COO-phenyl, COO-halophenyl, CO-(C1 -3-alkyl), CO-(C1-3-haloalkyl), CO-phenyl, or CO-halophenyl, more preferably COO-(C1 -3-alkyl), and in particular COO-methyl.

[0059] In one embodiment, Rpis C1 -4-alkyl, C1-4-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6-halo- carbocyclo, preferably C1 -3-alkyl, C1-3-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6-halocar- bocyclo, more preferably C1 -3-alkyl, C1-3-haloalkyl, phenyl, halophenyl, and in particular methyl, trifluoromethyl, or phenyl.

[0060] In one embodiment, RQis H, C1 -4-alkyl, C1-4-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6- halocarbocyclo, preferably H, C1 -3-alkyl, C1-3-haloalkyl, aryl, haloaryl, C4-6-carbocyclo, or C4-6- halocarbocyclo, more preferably H, C1 -3-alkyl, C1-3-haloalkyl, phenyl, halophenyl, and in particular H, methyl, trifluoromethyl, or phenyl.

[0061] In one embodiment, R3 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, preferably H, C1 -3-alkyl, or C1-3- haloalky, and in particular H.

[0062] In one embodiment, R1 in the compound of formula (1) is in meta position to SO2NH2.

[0063] In one embodiment, R2 in the compound of formula (1) is in ortho position to SO2NH2.

[0064] In a preferred embodiment, the compound of formula (1) is a compound of formula (1-1)

[0065] (1-1).

[0066] In one embodiment, the isocyanate-containing compound is a compound of formula (2)

[0067] In one embodiment, R1 in the compound of formula (2) is in meta position to SO2NCO. In one embodiment, R2 in the compound of formula (2) is in ortho position to SO2NCO.

[0068] In a preferred embodiment, the compound of formula (2) is a compound of formula (2-1)

[0069] (2-1).

[0070] In one embodiment, the process comprises the step of reacting a compound of formula (1-1)

[0071] (1-1) with oxalyl chloride, wherein the isocyanate-containing compound is a compound of formula (2-1)

[0072] (2-1), and wherein

[0073] R1 is halogen, C1-6-alkyl, or C1-6-haloalkyl, preferably Cl, Br, I, C1-3-alkyl, or C1-3-haloalkyl, more preferably Cl, Br, or I, and in particular I; and

[0074] R2 is COO-(C1-6-alkyl), COO-(C1-6-haloalkyl), COO-aryl, COO-haloaryl, CO-(C1-6-alkyl), CO-(C1- 6-haloalkyl), CO-aryl, or CO-haloaryl, preferably COO-(C1-3-alkyl), COO-(C1-3-haloalkyl), COO- phenyl, COO-halophenyl, CO-(C1-3-alkyl), CO-(C1-3-haloalkyl), CO-phenyl, or CO-halophenyl, more preferably COO-(C1-3-alkyl), and in particular COO-methyl.

[0075] In one embodiment, R1 is Cl, Br, or I, and R2 is COO-(C1-3-alkyl), preferably R1 is I and R2 is COO-methyl.

[0076] In one embodiment, the reaction is conducted under elevated temperature, preferably in a range of about 80 to about 200 °C, more preferably of about 85 to about 180 °C, still more preferably of about 90 to about 170 °C, and in particular of about 100 to about 160 °C such as about 120 to about 140 °C.

[0077] In one embodiment, the reaction is conducted in the presence of a solvent, preferable selected from the group consisting of chlorinated solvents, hydrocarbon solvents, ether solvents, pyridine, and mixtures thereof. The person skilled in the art is aware of suitable chlorinated solvents, hydrocarbon solvents, ether solvents. Suitable examples of chlorinated solvents are 1 ,2-dichloroethane, chlorobenzene, dichlorobenzene, and trichlorobenzene. Suitable examples of hydrocarbon solvents are cycloheptane, cyclohexane, cyclohexene, cyclooctane, cyclopentane, decalin, dodecane, durene, heptane, hexane, isopar M (C13-C14 isoparafin), kerosene, ligroin, limonene, mesitylene, methylcyclohexane, naphtha, 1 -octadecene, pentamethylbenzene, pentane, petroleum benzene, petroleum ether, toluene, tridecane, turpentine, white spirit, and xylene. Suitable ether solvents are tert-amyl ethyl ether, cyclopentyl methyl ether, di-tert-buty I ether, di(propylene glycol) methyl ether, dibutyl ether, diethyl ether, diisopropyl ether, dimethoxyethane, dimethoxymethane, 1 ,4-dioxane, ethyl tertbutyl ether, methoxyethane, 2-(2-methoxyethoxy)ethanol, methyl tert-butyl ether, 2-methyltetrahy- drofuran, morpholinepolyethylene glycol, propylene glycol methyl ether, tetrahydrofuran, tetrahydrofurfuryl alcohol, tetra hydro pyran, and 2,2,5,5-tetramethyltetrahydrofuran.

[0078] In one embodiment, the solvent is selected from the group consisting of 1 ,2-dichloroethane, chlorobenzene, dichlorobenzene, trichlorobenzene, xylene, toluene, pyridine, 1 ,4-dioxane, and mixture thereof, more preferably selected from the group consisting of xylene, toluene, and mixture thereof, and in particular xylene.

[0079] In one embodiment, the mixture of the solvent and the compound of formula (1) is a solution or a suspension, preferably a suspension.

[0080] In one embodiment, the reaction is free of a metal-based catalyst.

[0081] In one embodiment, the reaction is free of an amine-based catalyst. Such embodiment provides numerous benefits, as amine-based catalysts are often costly and can produce unpleasant odors.

[0082] In one embodiment, the reaction is free of phosgene. Such embodiment also provides a benefit to the present invention, as phosgene is a highly toxic compound, even in small amounts.

[0083] In one embodiment, the process comprises a step (a) of adding the oxalyl chloride to the compound of formula (1), which is optionally mixed with a solvent, and a step (b) of heating the mixture obtained in step (a), preferably to a temperature in a range of about 80 to about 200 °C, more preferably of about 85 to about 180 °C, still more preferably of about 90 to about 170 °C, and in particular of about 100 to about 160 °C such as about 120 to about 140 °C.

[0084] In one embodiment, the process is conducted at a pressure of about 0.1 to about 10 bar, preferably of about 0.4 to about 5 bar, more preferably of about 0.6 to about 2 bar, and in particular of about 0.8 to about 1 .5 bar.

[0085] In one embodiment, the process is conducted at atmospheric pressure. In one embodiment, the process is conducted for about 10 to about 40 hours, preferably for about 15 to about 35 hours, more preferably for about 15 to about 25 hours or for about 20 to about 35 hours, and in particular for about 24 to about 32 hours.

[0086] In one embodiment, the oxalyl chloride is provided in excess.

[0087] In one embodiment, the molar ratio of the oxalyl chloride to the compound of formula (1) is of about 40:1 to about 1 :1 , preferably of about 20:1 to about 2:1 , more preferably of about 15:1 to about 4:1 , still more preferably of about 12:1 to about 6:1 and in particular of about 10:1 to about 7:1 .

[0088] The present invention provides a safe and easily accessible way to a starting material of a process for preparing a compound of formula (3) wherein R1 , R2, and R3 are as defined above; the process comprising

[0089] (i) the process as defined above to obtain the isocyanate-containing compound as defined above, and

[0090] (ii) reacting the isocyanate-containing compound obtained in step (i) with an amine having the formula (4)

[0091] A-NH2 (4), wherein

[0092] A is an aryl or a heteroaryl, wherein each substitutable carbon or heteroatom in the aforementioned groups is independently unsubstituted or substituted with one or more, same or different substituent RA; and

[0093] RAis halogen, C1-C6-alkyl, C1-6-haloalkyl, C1-6-alkoxy C1-6-haloalkoxy, or CN.

[0094] The isocyanate-containing compound may be the compound of formula (2)

[0095] (2-1).

[0096] A may be an aryl, preferably phenyl or naphthyl.

[0097] RAmay be halogen, C1-C5-alkyl, C1-5-haloalkyl, C1-5-alkoxy, C1-5-haloalkoxy, or CN, preferably F, Cl, Br, C1-C3-alkyl, C1-3-haloalkyl, or C1-3-alkoxy, more preferably F, Cl, C1-C3-alkyl, or C1-3- alkoxy, and in particular C1-C3-alkyl or C1-3-alkoxy such as methyl or methoxy.

[0098] A may be a heteroaryl, e.g. comprising at least one nitrogen atom such as comprising at least two nitrogen atoms such as two or three nitrogen atoms.

[0099] A may be thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, furazanyl, pyridyl (pyridinyl), pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, and pyrrolopy ridiny I, in particular triazinyl.

[0100] The amine having the formula (4) may be a compound of formula (4-1)

[0101] (4-1), wherein RAis independently halogen, C1-C6-alkyl, C1-6-haloalkyl, C1-6-alkoxy C1-6-haloalkoxy, or CN, preferably C1 -3-alkyl, C1-3-haloalkyl, or C1-3-alkoxy, more preferably C1 -3-alkyl or C1-3-alkoxy, and in particular methyl or methoxy.

[0102] The compound of formula (3) may be a compound of formula (3-1)

[0103] (3-1) such as

[0104] It will be obvious for a person skilled in the art that these embodiments and items only depict examples of a plurality of possibilities. Hence, the embodiments shown here should not be understood to form a limitation of these features and configurations. Any possible combination and configuration of the described features can be chosen according to the scope of the invention.

[0105] The present invention will be further illustrated by the following examples.

[0106] Examples

[0107] Example 1

[0108] To a suspension of methyl 4-lodo-2-sulfamoylbenzoate (7 g) in Xylene (125 mL) under nitrogen at- mosphere, Oxalyl chloride (23 g) was added and the resulting mixture was refluxed to 120 °C for

[0109] 16 h. After concentration in vacuo, the residue was diluted with Xylene (35 mL) to give a solution of methyl 4-lodo-2-(isocyanatosulfonyl)benzoate.

[0110] This isocyanate solution can be further reacted to lodosulfuron as per the known in the art production process to give lodosulfuron in about 60% yield. Example 2

[0111] To a suspension of methyl 4-lodo-2-sulfamoylbenzoate (7.3 g) in Xylene (125 mL) under nitrogen atmosphere, Oxalyl chloride (24 g) was added and the resulting mixture was refluxed to 110-124 °C for 28 h. After concentration in vacuo, the residue was diluted with Xylene (38 mL) to give a solution of methyl 4-lodo-2-(isocyanatosulfonyl)benzoate.

[0112] This isocyanate solution can be further reacted to lodosulfuron as per the known in the art production process to give lodosulfuron in about 80% yield.

Claims

Claims1 . A process for preparing an isocyanate-containing compound, the process comprising the step of reacting a compound of formula (1)(1), wherein R1 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, aryl, haloaryl, C3-8-cy- cloalkyl, C3-8-halocycloalkyl, O(CO)-RM, NRMRN, or NH(CO)RM;R2 is COO-RP, CO-RP, CONRPRQ, or CN;R3 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, aryl, haloaryl, C3-8-cy- cloalkyl, C3-8-halocycloalkyl, O(CO)-RM, NRMRN, or NH(CO)RM, COO-RP, CO-RP, CONRPRQ, or CN;RMis C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl;RNis H, C1-6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl;Rpis C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl;RQis H, C1 -6-alkyl, C1-6-haloalkyl, aryl, haloaryl, C3-8-cycloalkyl, or C3-8-halocycloalkyl; with oxalyl chloride, wherein the reaction is substantially free of an amine-based catalyst, and wherein the reaction is substantially free of phosgene.

2. The process according to claim 1 , wherein the isocyanate-containing compound is a compound of formula (2)(2-1).

3. The process according to claim 1 or 2, wherein R2 in the compound of formula (1) is in ortho position to SO2NH2.

4. The process according to any one of claim 1 to 3, wherein R1 is not H, preferably whereinR1 in the compound of formula (1) is in meta position to SO2NH2, and in particular wherein the compound of formula (1) is a compound of formula (1-1)(1-1).

5. The process according to any one of claims 1 to 4, wherein R1 is halogen, C1 -6-alkyl, or C1-6-haloalkyl, preferably Cl, Br, I, C1 -3-alkyl, or C1-3-haloalkyl, and in particular I; and / or wherein R2 is COO-(C1 -6-alkyl), COO-(C1-6-haloalkyl), COO-aryl, COO-haloaryl, CO-(C1 -6-alkyl), CO-(C1-6-haloalkyl), CO-aryl, or CO-haloaryl, preferably COO-(C1 -3-alkyl), COO-(C1-3-haloalkyl), COO-phenyl, COO-halophenyl, CO-(C1 -3-alkyl), CO-(C1-3-haloalkyl), CO-phenyl, or CO-halo- phenyl, and in particular COO-methyl; and / orwherein R3 is H, halogen, C1 -6-alkyl, C1-6-haloalkyl, preferably H, C1 -3-alkyl, or C1-3-haloalky, and in particular H.

6. The process according to any one of claims 1 to 5, wherein the reaction is conducted under elevated temperature, preferably in a range of about 80 to about 200 °C, more preferably of about 85 to about 180 °C, more preferably of about 90 to about 170 °C, and in particular of about 100 to about 160 °C.

7. The process according to any one of claims 1 to 6, wherein the reaction is conducted in the presence of a solvent, preferable selected from the group consisting of chlorinated solvents, hydrocarbon solvents, ether solvents, pyridine, and mixtures thereof, more preferably selected from the group consisting of 1 ,2-dichloroethane, chlorobenzene, dichlorobenzene, trichlorobenzene, xylene, toluene, pyridine, dioxane, and mixture thereof, and in particular wherein the solvent is xylene.

8. The process according to claim 7, wherein the mixture of the solvent and the compound of formula (1) is a solution or a suspension, preferably a suspension.

9. The process according to any one of claims 1 to 8, wherein the process is conducted at a pressure of about 0.1 to about 10 bar, preferably of about 0.4 to about 5 bar, more preferably of about 0.6 to about 2 bar, and in particular of about 0.8 to about 1 .5 bar.

10. The process according to any one of claims 1 to 9, wherein the compound of formula (1) is a compound of formula (1-1)(1-1) and the isocyanate-containing compound is a compound of formula (2-1)(2-1) wherein R1 is halogen, C1 -6-alkyl, or C1-6-haloalkyl, preferably Cl, Br, I, C1 -3-alkyl, or C1-3-haloal- kyl, and in particular Cl, Br, or I; and wherein R2 is C00-(C1 -6-alkyl), COO-(C1-6-haloalkyl), COO-aryl, COO-haloaryl, C0-(C1 -6-alkyl), CO-(C1-6-haloalkyl), CO-aryl, or CO-haloaryl, preferably C00-(C1 -3-alkyl), COO-(C1-3-haloalkyl), COO-phenyl, COO-halophenyl, C0-(C1 -3-alkyl), CO-(C1 -3-haloalkyl), CO-phenyl, or CO-halo- phenyl, and in particular COO-(C1 -3-alkyl).11 . The process of claim 10, wherein R1 is I and R2 is COO-methyl.

12. The process according to any one of claims 1 to 11 , wherein the molar ratio of the oxalyl chloride to the compound of formula (1) is of about 40:1 to about 1 :1 , preferably of about 20:1 to about 2:1 , more preferably of about 15:1 to about 4:1 , still more preferably of about 12:1 to about 6:1 and in particular of about 10:1 to about 7:1.

Images