GB2203426A

GB2203426A - S-triazine derivatives

Info

Publication number: GB2203426A
Application number: GB08804056A
Authority: GB
Inventors: John Martin Farrar
Original assignee: Sandoz AG
Current assignee: Sandoz AG
Priority date: 1987-02-24
Filing date: 1988-02-22
Publication date: 1988-10-19
Also published as: JPS63233979A; IT8847657A0; GB8704328D0; IT1219842B; GB8804056D0; CH676000A5; FR2611365A1; DE3805513A1

Description

q L -4 2203426 IMPRMEMENTS IN CR RELATING TO ORGANIC COMPOWDS Case

370-5158/F/C The invention relates to a method for preparing asymetric triazinyl- oontaining stilbene derivatives.

According to the invention,, there is provided a process for 5 preparing a ccmpound of formula I, R 3 H R NH H=CH 0 N in which R is -NR5R6, -SCH3, halogen or -W5; (I) Rl has a significance of R,, independent of R, R5 is hydrogen; phenyl,, unsubstituted or substituted by one or two halogen atans,, Cl-4alkoxy,, sulpho,, mono- or di-(C1-4alkyl)-,amino or Cl-4alkyl groups; Cl-4alkyl unsubstituted or monosubstituted by hydroxy,, Cl-4alkoxy or cyano; -f-CH2-CH(R10a)-01m-RlO; -(Cl-4alkylene)-CCN(R10)2; -(CH2)p-N(R10)2 or -±CH2)p-N")(R10)3 Ae j Case 370-5158 where R10 is hydrogen or Cl-4alkyl, m is an integer f ran 1 to 10 inclusive, p is an integer fran 1 to 4 inclusive, R10a is hydrogen or methyl and AG is an anion; R6 is hydrogen; unsubstituted Cl-4alkyl; phenyl unsubstituted or substituted by one Cl-4alkyl group; C2-4alkyl substituted by one hydroxy, Cl-4alkoxy or cyano group; -±CH2CH(Rloa)-0-1m-Rjo; -(Cl4alkylene)-CCN(Rlo)2; -(CH2-)p-WR10)2 Or -(CH2)p-tlo (R103 AP where R10,, R10a,, p,, Ae and m are as defined above; or RS and R6 together with the N-atan to which they are 10 attached form a saturated heterocyclic amine group; canprising a) reacting one mole of a cund of formula II so 3 H with 2 moles of a canpound of formula III hal ogen N 0 1 haloggen (III) to form a caq=nd of formula I,, where R is halogen and Rl is as defined above; and b) optionally further reacting with a campound of formula IIIa H-Ra (IIIa) where R' is --NR R, -SCH' or OR a 5 6 3 5 to form a canpound of formula I where Rl is as defined above and P is selected fram,, -SCE3 and ^.

According to one aspect of the invention,, there is provided a process camprising 1 1 - 3 Case 370-5158 a) reacting one mole of a compound of formula n as defined above with 2 moles of a compound of formula III as defined above where Rl is halogen to form a compound of formula I where R and Rl are halogen; b) optionally reacting the compound of formula I where R and Rl are halogen with a compound of formula Inb H-Ria (IIIb) where Rla is -NRS R6r -SCH3 or -CEtS; and c) optionally reacting the compound of formula I where R is halogen and Rl is Rja defined above; with a compound of formula IIIa H-Ra (IIIa) where Ra is -NP.5 R6g, -SCE3 Or -<RS,, to form a compound of formula I where Rl is Rla defined above and R is Ra where Ra is defined above.

1 Further,, the reaction of H-Ra and H-Rla with a compound of formula I where R and Rl are halogen can be carried out at the same time or in separate steps.

Preferably the reaction of the compound of formula II with that of formula III where Rl is halogen. is carried out at a pH from 1.5 to 6. more preferably 2 to 5.5. Preferably the tenperature of the reaction of the compound of formula II with that of formula III is from - 150C to +SOC. more preferably from -SOC to +20C. Preferably the reaction of the compound of formula II with that of formula III is carried out in one or more solvents selected from a) aqueous ketones 1 Case 370-5158 (such as methylethyl ketone or acetone), b) chlorinated hydrocarbons in water and c) water, a wetting agent (such as a sulphosuccinate) and one or more Cl-4alcohols (such as isopropanol or n-butanol). Usuallyi the yield is 95 to 99 % of theory.

Wherp. R and RI in a compound of formula I is halogen and the first halogen is reacted.with H-Rlas, the pH is preferably fran 4-8,, more preferably fram 5 to 7 and the temperature of the reaction is preferably from 2 to 650C 9 more preferably fram 10 to 400C. Usually the yield is 95 to 99 1 of theory.

Where both R and Rl in a campound of formula I are halogen and second halogen group is r eacted with H-Ra,, the pH is preferably from 7 to 10. more preferably fram 7.5 to 8.5 and the temperature of the reaction is preferably from 40 to 1000C. Usually the yield is 95 to 99 % of theory.

For the reaction of the ciampounds of formula I with H-Ra and H-R Ia described abover the same solvent systems can be used as for the reaction of the compound of formula II with that of formula III.

For the avoidance of doubty in this Specification,, where a range is given in this Specification,, the nrs defining the range are included in the range.

According to another aspect of the invention. there is provided a process for preparing a compound of formula I,, in which R is Ra where Ra is r 7ME3 or -MS and Rl is Rla where Rla has a significance of R,, and in which both groups Ra are the same and both groups Rla are the same but Rla is different to Ra,, c=prising reacting:

a) 2 moles.of cyanuric halide (preferably cyanuric chloride) with 2 moles of H-Rlto form a ccmpound of formula XX is 1 F la N (0-- N- h &I og e n hal ogen Case 370-5158 (XX) b) reacting 2 moles of the ccffd of formula XX with 1 mole of the campound of formula ii H2N--H..CNN2 so 3 H.

to form a ca of formula YM R la N so 3 H N R la NH-H=CH W-- 0 1 al ogen N=( (XX I) alogen and c) reacting 1 mole of the cempound of formula M with 2 moles of H-Ra to form a com pound of formula I where R is Ra and Rl is Rja an defined above.

Preferably in the above reactions, R is % where Ra is anilino or morpholino and preferably Rl is Rja where Rja is anilino or morpholino.

Preferably the reaction of cyanuric halide with H-Rlayhere Rja is as defined above (preferably anilino or morpholino)o, is carried out in methylethyl ketone or acetone. Preferably the temperature of this reaction is from -150C to +SOC. The yield is usually 95 to 99 of theory. Preferably the pH is from I to.4.

- 6 Case 370-5158 Preferably the reaction of the ccimpound of formula XX with the compound of formula II is carried out at 10-400C and preferably at a pH of 5 to 7. Preferably the cnd of formula II is added as an aqueous slurry to the cnd of formula XL Usually. the yield is 95 to 99 % of theory.

Preferably the keaction of the ccmpcund of formula X= with H-Ra where Ra is as defined above (preferably morpholino or anilino (depending on R1) is carried out at a temperature of from 40-1006C preferably 50-800C (where necessary under reflux) and the PE is preferably fran 7-10. The reaction may be carried out with the addition of KCH or NaOH. Usually the yield is 95 to 99 % of theory.

Preferably when Rl is -CR5 where R5 is Cl-4alkyl, the reaction of cyanuric halide with H-Rl is carried out in a cl-4alcohol,, preferably in the presence of sodium bicarbonate. Preferably the temperature of this reaction is fran-15 to +50CUsuallyp the yield is 95 to 99 % of theory.

Preferably when R is --MS (but different to R1) where R_5 is other than Cl-4alkyl then the reaction of the ciampound of formula m with H-Mis carried out frcm 60-1000C. Preferably the reaction is carried out in the presence of sodium hydroxide. Usually. the yield is 90 to 95 % of theory.

Alternatively,, according to another aspect of the invention,, there is provided a process for preparing a cnd of formula I, as defined above where both groups R and/or both group Rl are -X6H5 cimprising:

a) reacting 2 moles of cyanuric halide with 1 mole of the compound of formula II; and b) reacting the product with 2 or 4 moles of phenol.

Case 370-5158 Preferably the reaction step a is carried out as described above at -15C to +5C and the reaction step b) is carried out at 50 to 800C, preferably in a solvent selected from methylethyl ketone or acetone. Usually the yield is 95 to 99 % of theory.

Cempounds of formula I can alternatively be formed by reacting 5 1 mole of the cempound of formula II with 2 moles of cyanuric halide (preferably cyanuric chloride) and then reacting the product either with 2 moles of aniline followed by 2 moles of morpholine or 2 moles of morpholine followed by 2 moles of aniline to form a compound of formula I in which both groups Rl are unsubstituted morpholino and both groups R are unsubstituted anilino. Usually the yield of the process is 90 to 95 % of theory.

Preferably R is R' where R' iS -NH2r -WR6')2, -NHR5', -SCHP halogen,, _5 5 N-(CH)-CH -OR 2 n -, 8 9 -0-C 0 or a saturated heterocyclic amine group attached to the triazinyl group through the N-atem; where R4 is hydrogen or methyl, R51 and R61 are defined below and R8 is hydrogen,. Cl-4alkyl or C2-4alkyl substituted by -M or Cl-4alkoxy and n is 0. 1 or 2. More preferably R is R' where R is -NH(R5% -N(R6')2, (where R51 and R61 are defined below) or a saturated heterocyclic amine group attached to the triazinyl group through the N-atam.

Preferably Rl is Rll where R11 has a significance of R', independent of W; more preferably Rl is R1w where Rll has a significance of R independent of R.

Case 370-5158 Preferably both groups R are the same and both groups Rl are the same.

Preferably R is not the same as Rl on the same triazinyl group.

Preferably in a Process accorcling to the inVentions in the a 5 canpound of formula I p R R 1 and R, is R, 11 where R 1 and Rl re as defined aboYee tPreferably R' is W' and R. is R I " defined above.

More preferably R is unsubstituted anilino, and Rl is more preferably unsubstituted morpholino.

Preferred heterocyclic amine groups are unsubstituted morpholino,, unsubstituted piperazinyl; unsubstituted N-methyl piperazinyl;.unsubstituted pyrrolidinyl and unsubstituted piperidinyl.

Preferably R4 is hydrogen.

Preferably R5 is R51 where R51 is phenyly unsubstituted or substituted by one or two halogeny Cl-4alkoxyi sulpho or Cl-4alkyl groups; or is clalkyl,, unsubstituted or monosubstituted by one hydroxy,, Cl-4alkoxy or cyano.

more preferably R5 is RSO where R51 is phenyl,, unsubstituted or substituted by one chloror methyl# methoxy or sulpho group; or is Cl4alkyl or C2-4hydroxyalkyl. Most preferably PS is unsubstituted phenyl.

Preferably the sulpho group in the stilbene group is ortho to the ethene group.

Preferably R6 is R61 where R61 is unsubstituted Cl-4alkyl or C2-4alkyl monosubstituted by Cl-4alkoxys, cyanor -CME2 or hydroxy; - 9 Case 370-5158 More preferably R6 is R61 where R61 is C2-4alkyl, unsubstituted or monosubstituted by hydroxy. or is methyl.

Preferred salt forms include alkali metal salts, alkaline earth metal salts and ammonium salts.

Still further according to the invention there is provided a process for preparing a compound of formula II camprising:

a) reacting a campound of formula iv CHO-1p-R12a R 3a OV) where R12a is NO2 or -NH-CO-CH3 and R3a is defined below with a compound of formula V NO 2 R 9 (V) R 3b where R9 is -CH2-P-(C1-2alkoXY)2# -CH3r -CH2M or -CH2COX1-6alkyl,and one of R3a and R3b is SO3H and the Other is hydrogen, to form a campound,, of formula VI 36 R 3a NO CH=C R 12a 2 (V I) and b) reducing and optionally hydrolysing the ompound of formula VI to form a compound of formula II.

j 4 Preferably when R9 in the cnd of formula V is -CH2-LC1-2alkoxy)2, R3b is hydrogen.

Case 370-5158 When a ompound of formula IV is reacted with a canpound of formula V where R9 is -CH2--(C1-2alkoxy)2,, preferably the pH of the reaction is frcin 8-14 (more peferably 12-14) and the reaction is carried out in the presence of a strong alkali (e.g. KOE or NaCE)._ The preferred temperature range of this reaction is frcm 10-1000C0 more preferably frm 20-400C. Preferred solvents for the reaction of a ccmpound of formula IV with that of formula V are polar aprotic solventar preferably dimethylformamide,, dimethylsulphoxide,, dimethylacetamide; and Cl-8alcohols e. g. isopropanol and ethoxyethanol. More preferred solvents are those selected fram dimethylformamide or dimethylsulphoxide; most preferred being dimethylformamide. - 'Usually the yield is 50 to 90 % of theory.

Mien a canpound of formula Mj, where R3a is -SO #, is reacted 4 3E with a ompound of formula V where R9 is -CH2M or CH2COX1-6alkyli, preferably the temperature of the reaction is fram 100-1600C and the pH is preferably fram 9-12. Preferably the solvent is dimethyl sulphoxide or a mixture of dimethylsulphoxide and petroleum spirit (b.p. 100-120OC). Preferably the reaction is carried out in the presence of a strong base,, for example piperidine,, piperazines, sodium carbonate or morpholinew 'Usually the yield is 40 to 80 % of theory.

Preferably when a compmM of formula iy is reacted with a cc of formula V where R3b is -SO3E and R9 is -CH2M or -CH2COX1-6alkyl,, the reaction is carried out in a Cl-6alcohol (e.g.

methanol or ethanol) or a C2-6 glycol ethoxyethanol or methoxy propanol; and when R3b is SO3H and P9 is CE3 then the reaction is carried out in dimethylformamide or dimethylsulphoxide. Preferably the pH of this reaction is fran 10-12 and preferably the trature Case 370-5158 range is from 50-150OCt more preferably from 70-1200C. Preferably this reaction is carried out in the presence of a catalyst. e.g. in the presence of a strong alkali such as piperidines piperazine, morpholine or sodium carbonate. usually the yield is 40 to 80 % of theory.

In the reaction of the compound of formula IY with a compound of formula V where R9 is -CH2M or -CH2CO0C1-6alkyl,, a compound of z formula XXIII 3b NO =CH R 12a WHI) A9a R 3a where R9a is -CN Or -=1-6alkylt is formed before formation of the corresponding compound of formula II.

The R9a group can be removed by hydrolysis as follows:

The M or CO0C1-6alkyl group is converted to -COOR the acid group by the ad dition of strong alkali (e.g. KOR or NaOH) and this acid group can be removed by heating the cnd of formula XXIII where Rga is -CO28 at a high temperature (e.g. 100-200OC) using powder.

Preferably reduction and/or hydrolysis of a ompound of formula VI to the corresponding meq=nd of formula II is carried out using sodium sulphide,, preferably at an elevated temperature,, more preferably 40 to 8010C. Reduction may also be effected by reacting a compound of formula VI with iron filingst at an.elevated temperature preferably 80-1206C, with an organic acidr e.g. acetic acid. Usually j the yield is 50 to 90 % of theory.

case 370-5158 ampounds of formula v where R9 is -CH2--(C1-2alkoxy) 2 and R 3b is -H can be prepared by reacting a compound of formula X R3b 9: CH 2-halogen (X) with a campound of formula VIII P(C1-2alkoxy)3 (VIII) to form a canpound of the formula XII 3b CH2-P(Ci-2alkoxy) 2 0 (M) which is then nitrated (preferably with fuming nitric acid) to form the ccmpound of formula V where R9 is -W2-P-(C1-2alkoxy)2.

Campounds of formula IV where R3a is -S03H and R12a is NO2r can be prepared by oxidising a campound of formula XV NO 2 - CH=CH -N02 F -,p R (XV) 3a R3a 9 preferably in an alcohol-containing solvent system. More preferably the solvent system is ethoxyethanol or the solvent system 1 Case 370-5158 is polyethylene glycol in water; most preferably the solvent system is polyethylene glycol in water. Preferably the molecular weight of the polyethylene glycol is fram 300 to 600. Preferably the reaction is carried out in the presence of an electrolyte. more preferably magnesium sulphate in water.

Preferably the pH of the oxidation reaction is fran 8 to 10 and preferably the temperature is fram 0 to 1000Cr more preferably frcin 0 to 500C. Preferred oxidising agents are potassium permanganater ozone. osmium tetraoxide,, lead tetraacetate. sodium permanganate or a mixture of potassium periodate and potassium permanganate. Oxidation may also be carried out electrochemically. Usually the yield is 30 to 80 % of theory.

Campounds of formulae II# Mr Y# and VIII can be made fran known ccgq=nds by kncim methods.

are known or The canpounds of formula I are useful as optical brighteners for addition to detergent csitions and for brightening of textile fabrics and paper. They can be used in the manner disclosed in Example 6 of US Patent 3,,895, ,009,, the disclosure of which is incorporated herein by reference.

in this Specification# any sulpho, group may be.in salt-form (preferably in alkali or alkaline earth metal salt form. more preferably the Na+ salt) or in free acid form. soweverp for- the sake of convenience any such sulpho group appearing in a formula has been shown in its free acid form,, except in the following Examples.

Case 370-5158 The invention will now be illustrated by the following Examples in which all temperatures are in OC.

Example 1

The campound of formula la CHO 0 -NO1 - 0 P-Na 3 (1a) can be prepared as follows:

A slurry of 235 9 of the ccxnpound of formula lb NO >- 0 CH=CH 0 -N02 SO Na 1, 2N 3 03 a Ub) 1000 g of water and 1000g of methoxypropanol are heated to reflux to form a clearsolution, which is then cooled to OC and a solution of 117 g of KM0 4 and 120 g of magnesium sulphate in 2000 g of water are added at CC over 1 hour. The precipitated HnO 2 is filtered off and the filtrates are concentrated until the aldehyde of formula la crystallises out and it is then filtered from the mother liquor.

Example 2 a) The ccmpound of formula 2a 0 R,---N-PO(OC,H)2 2 5 (2a) - is Case 370-5158 where R2O is -NO2, can be prepared as follows 791.2 9 of nitrobenzyl bramide are refluxed at 1300C with 669 9 of triethylphosphite in 1000 g of xylene. The ethylbrcmide resulting 5 is distilled off. 1000 g of the phosphonate of formula 2a result. Excess triethylphosphite and xylene can be removed by heating the mixture under vacuum.

b) 503 g of the compound of formula 2a (prepared above) are. mixed with 470 g of the cnd of formula la in 100 g of KOH and 10 10 litres of dimethylformamide.

The reactants are warmed slowly up to 5O0C and stirred for 3 hours under nitrogen and are poured onto an equal volume of water. The product that results is of formula 2b NO 2 CH=CH-P R 21 (2b) SO 3 Na where R21 is -NO2r and is filtered from the solution.

The above method can be repeated using 462.4 g of benzyl chloride instead of 791.2 g of nitrobenzyl bromide. However, prior to adding 503 g of the phosphonate to the compound of formula Ia,, the phosphonate is-nitrated as follows:

500 g of the phosphonate of formula 2a, where R20 is hydrogen, is added dropwise to 1000 g of ice cold fuming nitric acid,, over 1 hour at OOC. This is stirred for a further hour at OOC and the reaction mixture is poured onto 5000 9 of crushed ice. The organic phase is separated off and washed well with water. An equivalent amount of the compound of formula 2c Case 370-5158 CP.O-- ON M C CH3 (2c) 503Na may be used alternatively instead of 470 g of the canpound of formula la to form a cnd of formula 2br Where R21 is -NHCOCH3.

Example 3

L) 92 g of a wet cake containing the ccmpound of formula la (56.75% actives) are added to a slurry of 25 9 of sodium carbonate and 137 g of dimethylsulphoxide. The mixture is heated under vacuum and water is removed, after which the mixture is cooled to 900C. Then 33.2 g of pnitrotoluene. 7.14 g of piperidine and 46.8 g of 100/120 petroleum spirit are added.

The mixture is-subjected to slow azeotropic distillation and during which water of the condensation, dimethyl sulphoxide and sane piperidine seperate out fran the petroleum spirit distillate.

After about 10 hours,, 3.57 9 of piperidine is added and the mixture is refluxed for about 20 further hours. The reaction is cooled to 700 and the piperidine and petroleum spirit is distilled off under vacuum. The mixture is cooled to 506c. 65.6 g of methoxy propanol followed by 74.9 g of ethyl @cetate are added.

The mixture is warmed to 600 and a warm (6000 solution of 58.1 9 of sodium sulphide dissolved in 91.3 g of water is added dropwise over 2 hours at 80 to 850C.

83 g of 4 % of NaCl is added and the reaction is kept at 600C for 8 hours with slow stirring. The product of formula 3a N H 2 ---CH =C t- NN, SO 3 Na Case 370-5158 (3a) results.

ii) Alternativelyi 92 g of a wet cake containing the campound of formula la (56.4 % actives) are added to a slurry of 25 g of sodium carbonate and 200 g dimethylformamide. The mixture is heated under vacuum until the water is removed. 40 9 of 4-nitrophenylacetonitrile. 7 g of piperidine and 46.8 g of 100/120 petroleum spirit are added. The mixture is heated under azeotropic distillation for 5 hours. Piperidine and petroleum spirit are removed by vacuum distillation and 30 g of concentrated hydrochloric acid are added to the mixture. The mixture is refluxed for 10 hours, cooled and neutralized with sodium hydroxide solution. The precipitated nitro campound of formula 2b is filtered off.

Reduction to the amine of formula 3a may be carried out by reducing with sodium sulphide as above.

Example 3 ii) can be repeated using 54g of 4-nitrophenylacetic acid ethyl ester.instead of 40 g of 4-nitrophenylacetonitri.le.

Example 4

The campound of formula 4a @-NH NR--5 c0 NH H=CH 0 NH (4a) N N 0 3 Na 0 Case 370-5158 can be prepared from the compound of formula 3a defined in Example 3 as follows:

3449 9 of methyl ethyl ketone (MEK) in a first vessel are cooled to OOC. 493 g of cyanuric chloride is added whilst stirring 5 until it is fully dissolved in the MEK.

1379 g of demineralised water are placed in a second vessel and 758.8 g of a 50 % wet cake of the product of formula 3a (defined in Example 3) are added to the water whilst stirring. The resulting slurry is pumped onto the cyanuric chloride solution in the first vessel whilst maintaining the temperature from -20C to +20C and the pH between 4 and 5 by the addition of 138 g of sodium bicarbonate portion by portion. When the addition is finished 40 g of sodium bicarbonate are added to bring the pH to 6.5.

226 9 of aniline are added and 360 9 of a 30 % sodium hydroxide and 1000 g of water are slowly added to keep the pH between 6.5 and 7. The temperature it allowed to rise-When the reaction is ended and the temperature has risen to 300C with the pH at 6.5,, 440 9 of morpholine are added and the mixture is heated to 700C. 12 9 of sodium hydrosulphite are added to improve the colour.The mixture is refluxed and 3339 g of MEK are distilled off. The resulting mass is cooled to 500C and filtered and washed. The resulting product is the compound of formula 4a.

Example 5

By a method analogous with that of Example 3 i),. (via the Knoevenagel reaction) 1 mol of the compound of formula Sa Nor-.CHO (5a) - 19 Case 370-5158 is reacted with 1 mol of the canpound of formula 5b CH 0 -NO2 IP0Aa 3 (5b) to give 1 mol of the ccxnpound of formula 5c NOZ-.CH=CH 0 NO2 -P- 3 Na (5c) This is then reduced by a method analogous to that of Example 3i) to the ccmpound of formula 3a NH.2--(-CH=CH- N HZ 3 Na (3a) using sodium sulphide.

The cempound of formula Sa can be prepared by oxidation with potassium permanganate of the ccmpound of formula 5e or 5f NO E-H=CHCO 2 H (Se) 1 N02-H=CH--, (5f) according to known methods of Example 1. The cempound of formula 5b can be made by known methods fram known campounds.

Example 6

2.7 litres of methylethylketone are cooled to -150C and 142 9 of cyanuric chloride are added. 73 g of aniline are slowly added, keeping the temperature less than -30C. 40 g of sodium bicarbonate are then added followed by 110 g of the cnd of formula 6a; Case 370-5158 NH2 --CH=CH-P--NH 2 so 3 Na (6a) in a slurry in 1000 g of water. The pH is kept at 6 by the addition of dilute NaOH and the temperature is raised slowly to 650C. The pH is then adjusted to 7 and the reaction is diluted with 1.8 1 of water. 146 9 of morpholine are added followed by 10 9 of sodium hydrosulphate. The reaction is heated to reflux and 2.5 1 of methylethyl ketone are distilled off. The mixture is cooled and the product filtered off to give a 95 % yield of W"- --NH- O-NH-H=CH 0 0 N PON a h 0 _n 03Na Case 370-5158 CLkm: - 1. A process for preparing a campound of formula I R in which R is -NR5R6. -SCH3. halogen or -M5; 3 H R NH-C--H=CH-.H 0 N 2 1 Rl has a significance of RA, independent of R, R5 is hydrogen; phenyl,, unsubstituted or substituted by one or two halogen atans, Cl-4alkoxy, sulpho. mono- or di-(C1-4alkyl)-,wnino or Cl-4alkyl groups; Cl-4alkyl unsubstituted or monosubstituted by hydroxy. Cl-4alkoxy or cyano; -2- CH(R10a)-01m-"R10; -(Cl-4alkylene)-=(Rlo)2; -(CH2)p-N(R10)2 Or -±CH2)p- N')(R10)3 A9 where R10 is hydrogen or Cl-4alkyl, m is an integer frcm 1 to 10 inclusive, p is an integer fran 1 to 4 inclusivei R10a is hydrogen or methyl and AG is an anion; R6 is hydrogen; unsubstituted cl-4alkyl; phenyl unsubstituted or substituted by one Cl-4alkyl group; C2-4alkyl substituted by one 15 hydroxy,, cl-4alkoxy or cyano group; -[-CH2CH(R1()a)-0-1m-Rjo -(Cl-4alkylene)-CCN(Rlo)2; -(CH2-)p-N(R10)2 or -(CH2)p-O (R103 A9 where R10,, R1()ar pi AS and m are as defined above; or R5 and R6 together with the N-atan to which they are attached form a saturated heterocyclic amine group; canprising reacting one mole of a compound of formula II H2N--H=C 2 NH so 3 H with 2 moles of a canpound of formula III hal ogen N C0 1 alogen Case 370-5158 (III) to form a cempound of formula It Rl is as defined above and R is halogen; and optionally further reacting with a compound of formula IIIa H-Ra (ina) where R a is -NR5R6,, -SCH3 or ORS, to form a campound of formula I where R is R.a where R.a is selected frcm -NR5R6, -SCE3 and M5 and R, is as defined above.

Claims

2. A pr.ocess according to Claim 1 c=prising a) reacting one mole of a

ocmpound of formula II as defined to in Claim 1 with 2 moles of a ca of formula III as defined in Claim 1 where Rl is halogen to form a o=pound of formula I where R and Rl are halogen; b) optionally reacting the ccmpMM Of formula 1 where R and Rl are halogen with a cund of formula Mb H-Rla.. (IIIb) where Rla is -NRSNR6P -SCH3 or -MS; to form a compound of formula 1 where R 1 is R la and R is halogen; Case 370-5158 c) optionally reacting the compound of formula I where R is halogen and Rl is Rla defined above; with a cnd of formula Ma H-Ra (IIIa) where Ra is AR5R 6, -SCH 3 or -OR,; to form a compound of formula' -1 where-R Is Ra and R1 is R la as defined above.

3. A process according to Claim 1 or Claim 2, in which R is R' where R' is -NH2, -N(R6')2P -NHRS'r -SCH3r halogen,, % % or a saturated -N-(CH 2)-CH -OR 8 N heterocyclic amine group attached to the triazinyl group through the N- atan; where R4 is hydrogen or methyl,, PS' is phenyl,, unsubstituted or substituted by onie or two halogen, Cl-4alkoxy, sulpho or Cl-4alkyl groups; or is Cl-4alkyl,, unsubstituted or mono-substituted by hydroxy, Cl-4alkoxy or cyano; and R61 is unsubstituted Cl-4alkyl or C2-4alkyl monosubstituted by Cl-4alkoxy,, cyano,, -CM2 or hydroxy; and R8 is hydrogen, Cl-4alkyl or C2-4alkyl substituted by---0H or 15 Cl-4alkoxy and n is 0, 1 or 2.

4. A process according to Claim 3. in which Rl is R11 where R11 has a significance of R' defined in Claim 3# independently of the significance of RI.

5. A process according to Claim 1,, in which both groups R and 20 both groups Rl are the same.

6. A process according to Claim 5,, in which R and Rl on the same triazinyl are not the same.

i Case 370-5158 7. A process according to claim 1,, in which both groups Rl are morpholino and both groups R are anilino.

8. A process a cco rding to any one of the preceding claims in which the reaction of the compound of formula Ii with that of formula iii where RI is halogen, is carried out at a pH of 15 to 6 and a temperature of -150C to +50C.

9. A process according to any one of the preceding claims for preparing a compound where R and Rl are other than halogen in which when Rl and R are halogen and the first halogen is reacted with H-Ra,, the pE is from 4-8 and the temperature is from 2 to 650C and when the second halogen is reacted with H-Rjay the pE is 7 to W and the temperature of the reaction from 40 to 1000C.

10. A process for preparing a compound of formula I,, as defined in Claim l# in which R is Ra where Ra is -SCE3 or -CR5 as defined in Claim 1 and Rl is Rja where Rla is a significance of Rkindependently of R&rising.reacting a) 2 moles of cyanuric halide with 2 moles of H-Rla to form a compound of formula xX RIa h&l ogen hal ogen (XX) b) reacting 2 moles of the compound of formula XX with 1 mole 20 of the compound of formula II H 2 N --H=C-&NH2 so 3 H (I I) 1 1 1 to form a cempound of formula XXI R so 3 H NH-C-CH=CH R-- 0 0 N al ogen and Case 370-5158 (XX I) halocen c) reacting 1 mole of the compound of formula M with 2 moles of H-Pito form a ccmpound of formula I where R is Ra and R, is Rla as defined above.

11. A process according to Claim 10. in which both groups Ra are morpholino and both groups R1a are anilino.

12. A process according to Claim 10 or Claim 11,. in which the reaction of cyanuric halide with H-Rla-is carried out at -150C to -50C at a pH of 1-4.

13. A process according to any one of Claims 10 to 12. in which the reaction of a cnd of formula XX with that of formula II is carried out at a temperature of fran 10-SOOC and at a pH of 5 to 7.

14. A process according to any one of Claims 10 to 13,, in which the reaction of a compound of formula XXI with H-Ra is carried out at a temperature of 40-1000C and at a pH of 7-10.

15. A process for preparing a compound of formula I, defined in Claim lr in which both groups R and/or both groups Rl -are -X6H5 comprising a) reacting 2 moles of cyanuric halide with 1 mole of the - 26 cempound of formula II defined in Claim 1; and b) reacting the product with 2 or 4 moles of phenol.

Case 370-5158 16. A process according to Claim 15, in which reaction step b s caripied out at a temperature of fram 50 to 800C.

17. A process according to Claim 1. for preparing a c=pound of formula I, in which both groups R, are morpholino and both groups R are unsubstituted anilino camprising reacting:

a) 1 mole of a ccmpound of formula II with 2 moles of cyanuric halide; b) reacting the product either with 2 moles of aniline followed by 2 moles of morpholine or with 2 moles of morpholine followed by 2 moles of aniline.

18. A process for preparing a campound of formula II defined in Claim 1 ccmprising a) reacting a campound of formula iv CHO-IT-Rl 2a R 3a (IV) where R12a is NO2 or -NH-CO-M3 and R3a is defined below with a ompound of formula V NO 2 R 9 (V) 0 R 3b 1 where R9 is -CH2-P-(C1-2alkOXY)2# -CHI, -CH2CN or -CH2COX1-6alkyl and one of R3a and R3b is S03H and the other is hydrogen; to form a campoundr of formula VI i?.

3a R 3b NO CH=C RI 2a Case 370-5158 (V I) and b) reducing and optionally hydrolysing the compound of formula VI to form a cm of formula II.

19. A process according to Claim 18# in which in the campound 5 of formula Vr R9 is K52-f- (Cl-2alkoXY) 2 and in the Compound of 0 formula iv,, R3a is -W3Hp in which the reaction a) is carried out at a temperature of.frca 10-1000C and at a pE of 8-14.

20. A process according to Claim 18r in which in the c=pound of formula V, R9 it -CE3s, -cH2CN or -CH2C0Xl-6alkyl and R3b is hydrogen in which the reaction a) is carried out at a temperature of 100-1606C and at a pH of 912.

21. A process according to claim 17,, in which in the COMPOund of formulayp R9 is -<M3t -CE2M Or -<:a2c0Xl-6alkyl and R3b is -so H. in which the reaction is carried out at a pE of frcm 10-12 and at a temperature of frcm 50-1506C.

22. A process for preparing a ccimpound Of formula V where R 3 is -H and R 9 is -CH2-P(C1-2alkoxy)2 comprising reacting a 6= of formula X @H 2-halogen (X) - 28 Case 370-5158 with a compound of formula VIII P(C1-2alkoxy)3 (VIII) to form a compound of the formula XII Rib CH2-P,(C1-2a]koxy) 2 0 (M) which is then nitrated to form the compound of formula v defined in Claim 18F where R9 is---CH2-P-(Cl2alkoxy)2. 0 23. A process for preparing a compound of formula I as defined in claim 1, substantially as herein described with reference to any one of Examples 4 to 11 and 13.

24. A process for preparing a compound of formula II as defined in Claim 1. substantially as herein described with reference to Examples 3 and 12.

3700/D"C Published 1988 at The Patent Office, State House, 66171 High Holborn, London WC1R 4TP. Further copies may be obtained from The Patent Office, Sales Branch, St Mary Cray, Orpington, Kent BR5 3F.D. Printed by Multiplex techniques ltd, St Mary Cray, Kent. Con. 1187.