GB2156810A

GB2156810A - Sulphamoylimidocarbonate derivatives

Info

Publication number: GB2156810A
Application number: GB08507662A
Authority: GB
Inventors: Simon John Cousins; Jeffrey Daniel Michael; Barry Clive Ross
Original assignee: Hoechst UK Ltd
Current assignee: Sanofi Aventis UK Holdings Ltd
Priority date: 1984-03-27
Filing date: 1985-03-25
Publication date: 1985-10-16
Also published as: GB8507662D0

Abstract

Compounds of formula XXXI <IMAGE> in which R<31> and R<32>, which may be the same or different, each represents a hydrogen atom, a straight or branched chain alkyl group having from 1 to 4 carbon atoms, a cycloalkyl group having from 3 to 7 carbon atoms, a phenyl group, or a phenalkyl group having from 1 to 4 carbon atoms in the alkyl moiety, wherein an alkyl, cycloalkyl, phenyl or phenalkyl group may be unsubstituted or substituted; or R<31> and R<32> together with the nitrogen atom to which they are attached, form a 4- to 7-membered ring which may contain one or more further hetero-atoms, for example, selected from nitrogen, oxygen and sulphur atoms; L<3> and L<4>, which may be the same or different, each represents a group -XR<46> in which X represents an oxygen or sulphur atom and R<46> represents a straight or branched chain alkyl group having from 1 to 4 carbon atoms, an unsubstituted or substituted phenyl group, or an unsubstituted or substituted phenalkyl group having from 1 to 4 carbon atoms in the alkyl moiety, with the proviso that in L<3 >and L<4>, the two radicals R<46> may be the same or different but the two radicals X must be the same, are intermediates for sulphamoyl guanidines, sulphamoyl isothioureas and heterocyclic systems.

Description

SPECIFICATION Sulphamoylimidocarbonate derivatives and a process for their production The present invention relates to sulphamoylimidocarbonate derivatives, to a process for their production, and to their use in the production of pharmaceutically active compounds.

The present invention provides compounds of formula XXXI

in which R31 and R32, which may be the same or different, each represents a hydrogen atom, a straight or branched chain alkyl group having from 1 to 4 carbon atoms, a cycloalkyl group having from 3 to 7 carbon atoms, a phenyl group, or a phenalkyl group having from 1 to 4 carbon atoms in the alkyl moiety, wherein an alkyl, cycloalkyl, phenyl or phenalkyl group may be unsubstituted or substituted by one or more substituents, which may be the same or different, for example, by one or two substituents, especially by one substituent, selected from halogen atoms, straight or branched chain alkyl groups having from 1 to 4 carbon atoms, straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, and nitro and trifluoromethyl groups; or R3' and R32 together with the nitrogen atom to which they are attached, form a 4- to 7membered ring which may contain one or more further hetero-atoms, for example, selected from nitrogen, oxygen and sulphur atoms; L3 and L4, which may be the same or different, each represents a group - XR46 in which X represents an oxygen or sulphur atom and R46 represents a straight or branched chain alkyl group having from 1 to 4 carbon atoms, an unsubstituted or substituted phenyl group, or an unsubstituted or substituted phenalkyl group having from 1 to 4 carbon atoms in the alkyl moiety, wherein a phenyl or phenalkyl group may be substituted by one or two, and especially by one substituent, selected from alkyl, alkoxy, methylenedioxy, phenoxy, halogen, dialkylaminoalkyl (especially dimethylaminomethyl), trifluoromethyl, nitro, cyano, sulphonic acid, sulphonamide, amino, and mono- and di-alkylamino groups, an alkyl moiety having a straight or branched chain and from 1 to 4 carbon atoms, with the proviso that in L3 and L4, the two radicals R46 may be the same or different but the two radicals X must be the same, and with the exception of those compounds in which R31 and R32 both represent hydrogen atoms and L3 and L4 both represent alkylthio groups or both represent alkoxy groups.

Compounds of formula XXXI may exist in various isomeric and tautomeric forms. The present invention includes all isomeric and tautomeric forms of a compound of formula XXXI.

In the present specification, the term "lower" denotes groups having up to 4 carbon atoms, and any alkyl group can have a straight or branched chain.

in a compound of formula XXXI, R3' preferably represents a hydrogen atom, and R32 preferably represents a hydrogen atom or a lower alkyl group, especially a methyl group or an ethyl group. Particularly preferred are those compounds in which R3' represents a hydrogen atom and R32 represents a methyl group and especially preferred are those compounds in which R3' and R32 both represent hydrogen atoms.

When X in L3 and L4 represents a sulphur atom, L3 preferably represents a lower alkylthio group, especially a methylthio group, and L4 preferably represents a phenylthio group. When X represents an oxygen atom, L3 and L4 both preferably represent substituted phenoxy groups, especially mono-substituted phenoxy groups, for example, nitro-substituted phenoxy groups, for example, ortho-nitrophenoxy groups.

The following compounds of formula XXXI are particularly preferred: (1) R3' = R32 = hydrogen, L3 = methylthio and L4 = phenylthio, i.e. S-Methyl, S1-phenyl-N-sulphamoyldithioi midocarbonate (2) R31 = hydrogen, R32 = methyl, L3 = methylthio and L4 = phenylthio, i.e. S-Methyl, S'-phenyl N-(N'-methyl)-sulphamoyldithioimidocarbonate; (3) R3' = R32 = hydrogen, L3 = L4 = 2-nitrophenyloxy ie Bis-(2-nitrophenyl)-N-sulphamoylimidocarbonate; and (4) R3' = hydrogen, R32 = methyl, L3 = L4 = 2-nitrophenyloxy ie Bis-(2-nitrophenyl)-N-(N'-methyl)- sulphamoylimidocarbonate.

The present invention provides a process for the production of a compound of formula XXXI as defined above, that is to say, including those compounds in which R31 and R32 both represent hydrogen atoms and L3 and L4 both represent alkylthio or alkoxy groups, which comprises reacting a compound of the general formula XXXII

in which Y represents a halogen atom, especially a chlorine atom, and R31 and R32 are as defined above, with a compound of the general formula XXXIII or with a compound of the general formula XXXIV

in which R46 is as defined above.

A compound of formula XXXII may be prepared as described in Chem. Ber. 91, 1339, (1958), in DE-OS 937,645, J. Org. Chem. 414028(1976) or in J. Med. Chem. 15(5) 538 (1972), and is preferably used when freshly prepared. A compound of formula XXXIII may be prepared as described in Z. Chem. 8 (1 2) 459-460 (1968), Bull. inst. recherches biol unic.

Perm, 6, (10), 517-522, or Beilstein E113 page 156, and a compound of formula XXXIV as described in Liebig's Annalen 287 310, 319 and 321 (1895).

In a compound of formula XXXIII, one radical R46 preferably represents a methyl group and the other preferably represents a phenyl group. In a compound of formula XXXIV, both radicals R46 preferably represent substituted phenyl groups, for example, ortho-nitrophenyl groups.

The reaction between the compound of formula XXXII and the compound of formula XXXIII or XXXIV is preferably carried out in the presence of an organic base, especially a tertiary amino base, for example, triethylamine.

The reaction is preferably carried out in the presence of an aprotic solvent, for example, acetonitrile, or an ether, an aromatic hydrocarbon, a chlorinated aliphatic or aromatic hydrocarbon, for example, diethyl ether, tetrahydrofuran, benzene or dichloromethane.

The reaction is preferably carried out under an inert atmosphere, for example, under nitrogen.

The reaction is generally carried out at a temperature within the range of from - 50 to + 80"C, preferably from - 5 to + 45"C.

Preferably, a compound of formula XXXII, advantageously freshly prepared, is added dropwise to a solution of the compound of formula XXXIII or XXXIV, and the base is preferably added simultaneously with the compound of formula XXXII. This addition may be carried out over a period of from 5 minutes to 8 hours, preferably from 10 minutes to 2 hours.

Compounds of formula XXXI in which R3' and R32 both represent hydrogen atoms and L3 and L4 both represent alkylthio or both represent alkoxy groups are disclosed in UK Patent Specification No. 1 398 426, which discloses a different process which results in the production of those compounds of formula XXXI in which R3' and R32 both represent hydrogen atoms, and L3 and L4 both represent alkylthio groups only.

Compounds of formula XXXI are versatile intermediates which can be used in the production of a wide range of sulphamoyl guanidines, sulphamoyl isothioureas, sulphamoyl thioureas, and a variety of heterocyclic systems by displacement of the leaving group L3 and/or the leaving group L4 by a suitable group. For example, by reacting a compound of formula XLVI I

in which L3 and L4 are as defined above and R represents a hydrogen atom, a straight or branched chain alkyl group having from 1 to 4 carbon atoms, a phenyl group or a phenalkyl group, the alkyl moiety of which has a straight or branched chain and from 1 to 4 carbon atoms, wherein an alkyl, phenyl or phenylalkyl group may be unsubstituted or substituted by one or more substituents, which may be the same or different, for example, by one or two substituents, especially by one substituent, selected from halogen atoms, straight and branched chain alkyl groups having from 1 to 4 carbon atoms, straight and branched chain alkoxy groups having from 1 to 4 carbon atoms, nitro and trifluoromethyl groups; with an amine of formula XLVI HNR42R43 XLVI in which R42 and R43 are as defined for R, and R, R42 and R43 may be the same or different, there is produced a compound of formula XLIII

in which L3, R, R42 and R43 are as defined above.

A compound of formula XLIII may, in its turn, be reacted with a compound of formula XLV A~(CH2)n~X~(CH2)m~NH2 XLV in which A represents a phenyl or furyl radical, which radical may be unsubstituted or may have one or more, especially one or two, substituents which may be the same or different, selected from guanidino and mono-alkyl guanidino groups, the alkyl moiety of which has a straight or branched chain and from 1 to 4 carbon atoms, and from groups of formula II

in which Q represents an alkylene group having from 1 to 4 carbon atoms, and R' and R2, which may be the same or different, each represents a hydrogen atom, or a straight or branched chain alkyl group having from 1 to 4 carbon atoms, or R' and R2 together with the nitrogen atom to which they are attached form a 4 to 8-membered ring which may contain an oxygen atom or another nitrogen atom, which nitrogen atom may have an alkyl group having from 1 to 4 carbon atoms as substituent, or A represents a thiazolyl or thiadiazolyl radical that is substituted by one or more, especially by one or two, substituents which may be the same or different and which are as defined above for substituents of phenyl and furyl groups A; X represents an oxygen or sulphur atom; n represents 0 or 1; and m represents 2, 3 or 4, to give a compound of formula XLI

in which A, X, n, m, R, R42 and R43 are as defined above.

The reaction between compounds XLVII and XLVI, and between compounds XLIII and XLV, respectively, is generally carried out in a solvent, for example, an organic solvent, for example, a lower alcohol, for example, methanol, ethanol or isopropanol, dimethylformamide, tetrahydrofuran or acetonitrile, or in a mixture of two or more of such solvents. The reaction is generally carried out at a temperature within the range of from 5 to 75"C, especially at room temperature.

Compounds of formula XLI and processes for their production are described and claimed in our co-pending application no. 8507660 (Case 19). Compounds analogous to compounds XLI may be prepared analogously from other compounds of formula XXXI.

An example of the use of a compound of formula XXXI in the production of a heterocyclic system is as follows: A compound of formula XIV

in which R is as defined above, and R10 represents an alkoxy, phenoxy, phenylalkoxy, alkylthio, phenylthio or phenylalkylthio group wherein a phenyl or phenalkyl group may be unsubstituted or substituted by one or two substituents, which may be the same or different, selected from alkyl, alkoxy, methylenedioxy, phenoxy, halogen, dimethylaminomethyl, trifluoromethyl, nitro, cyano, sulphonic acid, sulphonamide, amino, mono-alkylamino and di-alkylamino groups, an alkyl moiety having a straight or branched chain and from 1 to 4 carbon atoms, is reacted with ammonia to give a compound of formula XV

in which R and R'O are as defined above.Compound XV is then reacted with a compound of formula XVI R'2-C(OR3)3 XVI in which R3 represents a straight or branched chain alkyl group having from 1 to 4 carbon atoms, and R12 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, a phenyl group or an -OR3 group, in which R3 is as defined above, to give a compound of formula XVII

in which R, R'O and R12 are as defined above.

A compound of formula XVII may then be reacted with a compound of formula IV E(CH2)n~X~(CH2)m~NH2 IV in which E represents a phenyl, imidazolyl, thiazolyl, furyl, thienyl, or pyridyl radical, which radicals may be unsubstituted or may have one or two substituents, selected from straight and branched chain alkyl groups having from 1 to 4 carbon atoms, guanidino and mono-alkyl guanidino groups, the alkyl moiety of which has a straight or branched chain and from 1 to 4 carbon atoms, and groups of the formula II

in which Q represents an alkylene group having from 1 to 4 carbon atoms, and R' and R2, which may be the same or different, each represents a hydrogen atom, a straight or branched chain alkyl group having from 1 to 4,carbon atoms or, together with the nitrogen atom to which they are attached, R' and R2 form a 4 to 8-membered ring which may contain an oxygen atom or another nitrogen atom, which nitrogen atom may have an alkyl substituent having from 1 to 4 carbon atoms, X represents -0- or -S-; n represents 0 or 1; and m represents 2, 3 or 4, to give a compound of formula la

in which R and R12 are as defined above, and W represents a group E-(CH2)-X-(CH2)m-NH- in which E, X, n and m are as defined above.

In formula la, alkyl groups may be branched or unbranched, and alkyl groups, for example, alkyl groups R4 and R5, may be unsubstituted or substituted, for example, by one or more, for example, one or two, groups selected from (i) -OP6 groups in which P6 represents a straight or branched chain alkyl group having from 1 to 6 carbon atoms; (ii) cycloalkyl groups having from 3 to 7 carbon atoms;; (iii) -NR7 R8 groups in which R7 and R8, which may be the same or different, each represents a hydrogen atom, a straight or branched chain alkyl group having from 1 to 4 carbon atoms, a phenyl group or an acyl group having from 1 to 4 carbon atoms in the alkyl moiety, and R7 and R8 together with the nitrogen atom to which they are attached may form a 5 or 6 membered ring; (iv) -COOR9 groups in which R9 represents a straight or branched chain alkyl group having from 1 to 4 carbon atoms; (v) -CONR7 R8 groups in which R7 and R8 are defined above; (vi) alkylsulphonyl groups having from 1 to 4 carbon atoms in the alkyl moiety and phenylsulphonyl groups; (vii) cyano and nitro groups;; (viii) phenyl groups which may be substituted by one or two substituents, which may be the same or different, selected from alkyl, alkoxy, methylenedioxy, phenoxy, halogen, dimethylaminomethyl, trifluoromethyl, nitro, cyano, sulphonic acid, sulphonamide, amino, mono-alkylamino and di-alkylamino groups, an alkyl moiety having a straight or branched chain and from 1 to 4 carbon atoms; (ix) aromatic and non-aromatic heterocyclic groups having from 5 to 8 ring members and one or two hetero-atoms selected from oxygen, sulphur and nitrogen atoms, and optionally having an alkyl substituent having from 1 to 4 carbon atoms on a ring nitrogen atom, for example, a furyl, tetrahydrofuryl, thienyl, pyridyl, dihydropyranyl, pyrrolidinyl, N-lower alkyl-pyrrolidinyl, or piperidyl group.

A phenyl group in formula la other than a phenyl group E (which is as defined above), may be unsubstituted or substituted as defined in (viii) above.

Compound XIV is generally reacted with one equivalent of anhydrous ammonia, preferably in an inert solvent, for example, tetrahydrofuran or dioxane, preferably at a temperature in the range of from 0 to 20"C to give compound XV, which is cyclised to the thiatriazine XVII by reaction with ortho ester XVI. This reaction may be carried out using an excess of the ortho ester as solvent or, preferably, using an inert solvent, for example, acetonitrile, tetrahydrofuran, dioxane or diglyme, preferably at an elevated temperature, for example, from 80 to 1 60'C.

Compound IV is generally reacted with compound XVII in a solvent or diluent, preferably in an alcohol, acetone, acetonitrile or DMF. The reaction temperature is, for example, within the range of from 0 to 80"C, depending on the nature of the leaving group R'O. Generally when R10 is a substituted phenoxy group, the reaction occurs rapidly at 0 to 20"C, but when R10 is an alkylthio or alkoxy group, elevated reaction temperatures, for example, in the range of from 50 to 100"C, for example, for 60 to 80"C are preferred.

The compound of formula IV is reacted in the form of the free base, as shown. If it is initially present in the form of an acid addition salt, for example, as the hydrochloride or hydrobromide, this is converted into the free base during or, preferably, before reaction with compound XVI I.

Conversion is carried out with an organic or inorganic base, for example, sodium hydroxide or potassium hydroxide, or a tertiary amine, for example, triethylamine.

The production of a compound of formula la from a compound of formula XIV is described and claimed in our Application No. 8507661 (Case 20), which application also describes and claims compounds XV, XVII and XLIII.

Compounds of formula XLI and of formula la have histamine H-2 antagonist activity, and may be used to treat conditions resulting from stimulation by histamine of H-2 receptors, either alone, for example, in inhibiting gastric acid secretion and thus treating its sequelae, for example, gastric and peptic ulcers; or together with H-1 antagonists, for example, in allergic and certain inflammatory conditions.

Compounds of formula XIV and XLVI I are particularly preferred compounds of formula XXXI.

The following Examples illustrate the invention. In the Examples, ratios of eluants are expressed by volume.

EXAMPLE 1 Bis-methyl-N-sulphamoyldithioimidocarbonate To a solution of 3.759 of dithioimidocarbonate dimethyl ester in 1 OOml of dry benzene, 4.35 ul of triethylamine and a solution of 3.589 of freshly prepared sulphamoyl chloride in 40ml of dry benzene were added dropwise simultaneously at 18"C, with vigorous stirring under an atmosphere of nitrogen. The addition was carried out over 30 minutes. After a further period of one hour at room temperature, the mixture was evaporated to dryness and triturated with chloroform. The resulting solid was filtered off and dried over silica gel: 3.379 m.p.

148-150"C. m/e 200.

EXAMPLE 2 Methyl, phenyl-N-sulphamoyl dithiolmidocarbonate To a solution of 8.699 of methyl, phenyl-dithioimidocarbonate in 1 75ml of dry benzene, 8.14ml of triethylamine and a solution of 6.679 of fresh prepared sulphamoyl chloride in 80ml of dry benzene were added dropwise simultaneously at 18"C with vigorous stirring under an atmosphere of nitrogen. The addition was carried out over a period of one hour. External cooling was applied to maintain the temperature of 18"C. After a further 1 6 hours at room temperature, 100ml of water and 1 00ml of diethyl ether were added and the mixture was stirred until all the solids had dissolved.The layers were then separated and the organic phase washed with water, dried over MgSO4, and then evaporated to give an oily solid which on trituration with benzene/hexane gave 4.59 of a colourless solid.

Crystallisation from chloroform gave needles, m.p. 125-126"C. m/e 262 H nmr 60MHz CDCl3 8: 2.40 (3H, s); 5.35 (2H, s. exch); 7.57 (5H, m).

EXAMPLE 3 Bis-(2-nitrophen yl)-N-sulphamoylimidocarbonate To a vigorously stirred solution of 1 5.0g of bis-(2-nitrophenyl)-imidocarbonate in a mixture of 200ml of dry benzene, 100ml of ether and 25ml of acetonitrile at 40"C, 7.6ml of triethylamine and a solution of 5.7g of freshly prepared sulphamoyl chloride in 70ml of dry benzene were added dropwise simutaneously over a period of 45 minutes. After one hour at room temperature, 100ml of water and 1 00ml of ethyl acetate were added to dissolve any solids present. The layers were then separated and the aqueous layer extracted with a further 100ml of ethyl acetate.The combined organic layers were washed with water, dried over MgSO4, and then evaporated to give an oily solid, which on triturationwith ether gave 6.0g of a pale yellow solid, m.p. 165-167'C.

'H nmr 60MHz DMSO-d8 d: 4.35 (2H, hump, exch); 7.1-8.3 (8H, m).

EXAMPLE 4 Bis-(2-nitrophenyl)-N-(N'-methyl)sulphamoylimido carbonate 6.069 of bis-(2-nitrophenyl)imido carbonate was dissolved in 150ml of dry methylene dichloride. 2.849 of methylsulphamoyl chloride and 2.20g of triethylamine were added dropwise simultaneously to this solution with rapid stirring. After having been stirred for 1 5 minutes, the reaction solution was washed twice with water, dried over MgSO4, and evaporated to a crystalline residue which was washed with ether and recrystallised from acetone/ether to give the title compound: 6.50g, m.p. 171-172"C.

XH nmr 60MHz DMOS-d8: 2.50 (3H, d), 7.1-8.3 (8H, m).

Claims

1. A compound of formula XXXI

in which R3' and R32, which may be the same or different, each represents a hydrogen atom, a straight or branched chain alkyl group having from 1 to 4 carbon atoms, a cycloalkyl group having from 3 to 7 carbon atoms, a phenyl group, or a phenalkyl group having from 1 to 4 carbon atoms in the alkyl moiety, wherein an alkyl cycloalkyl, phenyl or phenalkyl group may be unsubstituted or substituted by one or more substituents, which may be the same or different, for example, by one or two substituents, especially by one substituent, selected from halogen atoms, straight or branched chain alkyl groups having from 1 to 4 carbon atoms, straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, and nitro and trifluoromethyl groups; or R3' and R32 together with the nitrogen atom to which they are attached, form a 4- to 7membered ring which may contain one or more further hetero-atoms, for example, selected from nitrogen, oxygen and sulphur atoms; L3 and L4, which may be the same or different, each represents a group ~or46 in which X represents an oxygen or sulphur atom and R4s represents a straight or branched chain alkyl group having from 1 to 4 carbon atoms, an unsubstituted or substituted phenyl group, or an unsubstituted or substituted phenalkyl group having from 1 to 4 carbon atoms in the alkyl moiety, wherein a phenyl or phenalkyl group may be substituted by one or two, and especially by one substituent, selected from alkyl, alkoxy, methylenedioxy, phenoxy, halogen, dialkylaminoalkyl (especially dimethylaminomethyl), trifluoromethyl, nitro, cyano, sulphonic acid, sulphonamide, amino, and mono- and di-alkylamino groups, an alkyl moiety having a straight or branched chain and from 1 to 4 carbon atoms, with the proviso that in L3 and L4, the two radicals R46 may be the same or different but the two radicals X must be the same, and with the exception of those compounds in which R3' and R32 both represent hydrogen atoms and L3 and L4 both represent alkylthio groups or both represent alkoxy groups.

2. A compound as claimed in claim 1, wherein R31 represents a hydrogen atom, and R32 represents a hydrogen atom or an alkyl group having from 1 to 4 carbon atoms.

3. A compound as claimed in claim 1 wherein R31 represents a hydrogen atom and R32 represents a methyl group.

4. A compound as claimed in claim 1, wherein R3' and R32 both represent hydrogen atoms.

5. A compound as claimed in any one of claims 1 to 3, wherein L3 represents an alkylthio group having from 1 to 4 carbon atoms, and L4 represents a phenylthio group.

6. A compound as claimed in any one of claims 1 to 3, wherein L3 and L4 both represent substituted phenyl groups.

7. A compound as claimed in claim 6, wherein L3 and L4 both represent mono-substituted phenyl groups.

8. A compound as claimed in claim 1, wherein R31 = R32 = hydrogen, L3 = methylthio and L4 = phenylthio.

9. A compound as claimed in claim 1, wherein R3' = hydrogen, R32 = methyl, L3 = methylthio and L4 = phenylthio.

10. A compound as claimed in claim 1, wherein R31 = R32 = hydrogen, and L3 = L4 = 2nitrophenoxy.

11. A compound as claimed in claim 1, wherein R31 = hydrogen, R32 = methyl, and L3 = L4 = 2-nitrophenoxy.

1 2. A compound as claimed in claim 1, having the formula XIV

in which R represents a hydrogen atom, a straight or branched chain alkyl group having from 1 to 4 carbon atoms, a phenyl group or a phenalkyl group, the alkyl moiety of which has a straight or branched chain and from 1 to 4 carbon atoms, an alkyl, phenyl or phenalkyl group being unsubstituted to substituted by one or more substituents, which may be the same or different, for example, by one or two substituents, especially by one substituent, selected from halogen atoms, straight and branched chain alkyl groups having from 1 to 4 carbon atoms, straight and branched chain alkoxy groups having from 1 to 4 carbon atoms, nitro and trifluoromethyl groups; and R10 represents an alkoxy, alkylthio, phenoxy, phenylthio, phenylalkoxy or phenylalkylthio group.

1 3. A compound as claimed in claim 1, having the formula XLVI I

in which L3 and L4 are as defined in claim 1 and R is as defined in claim 1 2.

14. A process for the production of a compound of formula XXXI as defined in claim 1, including those compounds in which R3' and R32 both represent hydrogen atoms and L3 and L4 both represent alkyloxy or alkylthio groups, which comprises reacting a compound of formula XXXII

in which Y represents a halogen atom, and R3I and R32 are as defined in claim 1, with a compound of the general formula XXXIII or with a compound of the general formula XXXIV

in which R48 is as defined in claim 1.

15. A process as claimed in claim 14, wherein in a compound of formula XXXIII, one radical R48 represents a methyl group and the other radical R46 a phenyl group, and in a compound of formula XXXIV, both radicals R48 represent substituted phenyl groups.

16. A process as claimed in claim 14, carried out substantially as described in any one of Examples 1 to 4 herein.

17. A compound as claimed in claim 1 whenever produced by a process as claimed in any one of claims 14 to 16.

18. A compound as claimed in claim 1, substantially as described in any one of Examples 1 to 4 herein.

1 9. A compound as claimed in any one of claims 1 to 13, claim 1 7 and claim 18, for use in the production of sulphamoyl guanidines, sulphamoyl isothioureas, sulphamoylthioureas and heterocyclic systems.