TWI298325B - A process for the preparation of bis-benzazolyl compounds - Google Patents

Description

A7 1298325 V. INSTRUCTIONS (/) The present invention relates to a process for the preparation of bis-indenyl compounds which are useful as fluorescent whitening agents for natural or synthetic materials. Different methods of preparing such compounds are known. Thus, for example, U.S. Patent No. 4,508,903 describes the preparation of 4,4'-bis-benzoxazole-, benzothiazole- and benzimidazoles by relatively co-polymerization of -chloromethylphenyl hydrazines. 2-based stilbene diene. However, the preparation of such a process with intermediates involves several reaction steps, which in turn provides the disadvantage of substantially sparse production. A particular interest in practice is a process in which a dicarboxylic acid or a derivative thereof is reacted with a difunctional aromatic compound in a single reaction step to form a heterocyclic ring. Thus, for example, European Patent No. 31,296 is described in a solvent mixture consisting of diphenyl ether and biphenyl in the presence of an acidic catalyst by means of an organic carboxylic acid with o-aminophenols and adjacent- A method of preparing a benzoxazolyl and benzimidazolyl compound by condensation of phenylenediamines. Further, British Patent No. 1,201,287 is described, for example, in refluxing 1,2,4-trichlorobenzene in the presence of boric acid by thiophene-2,5-dicarboxylic acid and o-aminophenol. A method of preparing 2,5-bisbenzoxazol-2-ylthiophene by condensation. Such processes are disadvantageous because they require extremely high reaction temperatures, resulting in the formation of impurities that are difficult to remove from the final product and, therefore, loss of product yield. Further, such a high boiling point solvent is also difficult to remove from the reaction product and can further cause hard shell formation in the inside of the reaction vessel, thereby hindering the production of the final product. In addition, the use of chlorinated aromatic solvents in the present case is not desirable for ecological reasons. 4 -----------*t--------tl----------^^_wl (Please read the notes on the back and fill out this page) The paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1298325 A7

V. INSTRUCTIONS (乂) Surprisingly, a new and advantageous process for the preparation of bis-indolyl compounds has now been discovered which provides high yields of high purity under reaction conditions, suitable for commercial compounds. . Accordingly, the present invention provides a method of preparing a compound of the formula:

Wherein Y represents -0-, -s_ or -N(R2)_,: R2 is hydrogen, CkCm alkyl or aralkyl; Z represents 2,5-furanyl, 2,5-phenylthio, 4, 4'- stilbene group or 1,2-ethylenyl residue and

Ri represents hydrogen, halogen, and Ci-Ciq hospital base 'Ci-C〗. Alkyl cyano, C00M or S03M, hydrazine is hydrogen or an alkali metal or alkaline earth metal, characterized by an acid touch in N-methylpyrrolidone or hydrazine, hydrazine-dimethylacetamide In the presence of a medium, and optionally, in the presence of a second solvent capable of removing water from the reaction mixture, the compound of the formula αΝΗ2 (2) ΥΗ is dihydrated with the following formula of dicarboxylic acid H00C-Z-C00H ( 3) or its ester reaction, hydrazine, hydrazine and R! are as defined above. The molar ratio of the compound of the formula (2) to the compound of the formula (3) can be varied within a wide range. However, it is advantageous to react at least two moles of the compound of formula (2) with 5 paper grades applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 public f) ------------ Loading -------- Order --------- (Please read the notes on the back and fill out this page) 1298325 a7 _B7__ V. Invention description o ) At least one Moh (3) Dicarboxylic acid. Alternatively, a mono- or diester of the compound of formula (3), preferably a diester, can be used. Suitable esters are those derived from, preferably C "C4 alcohol, diethyl esters. The process of the invention is particularly suitable for the preparation of compounds of formula (1) wherein Y represents -0-, -S- Or -N(R2)-, R2 is hydrogen or cvc4 alkyl; Z is as defined above and K represents hydrogen or c"c4 alkyl and is more particularly suitable for the preparation of compounds of formula (1) wherein z represents 2,5 a furyl or 2,5-phenylthio residue and also those wherein Z represents a 4,4'-stilbene group or a 1,2-ethylenyl residue. The reaction medium of the method of the invention, N-methylpyrrolidone or N,N-dimethylacetamide or a mixture thereof is preferred. It is also possible to use N-methylpyrrolidone or N,N-dimethylacetamide together. Or a mixture thereof and another high-boiling inert solvent such as toluene or xylene. It is particularly preferred to use N-methylpyrrolidone. The acid catalyst used in the process of the present invention may be selected from the group consisting of boric acid, phosphoric acid, Among the groups of orthoester titanium or tin derivatives, boric acid or titanium of Ci-C4 orthoester, especially tetrapropyl or tetrabutyl ester, is preferred. The content may vary within a wide range and depends on the chemical entity. Therefore, for example, based on the content of the compound (2), the content may be different from 〇1 to 50 mol%, preferably 〇1 to 30 mol. % can be used. The reaction of the compounds of formula (2) and (3) can be carried out at a wide range of temperatures, but preferably in the range between 100 and 25 CTC, especially at 150 and 200. (: 6 paper scales Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) " -- ---I---装i丨丨丨丨丨丨定--------* (Please read the back first Note: Please fill in this page again) 1298325 B7 5. In the temperature range of invention (f) (Please read the notes on the back and fill in this page) When the compound of formula (3) is monoester or, in particular, The presence of the second solvent is particularly important in the form of the free dicarboxylic acid. In these examples, the water formed during the reaction can be continuously removed from the reaction mixture. Examples of suitable solvents do not limit their choice. , selected from the group consisting of toluene, xylenes and their isomeric mixtures with pyridine, toluene and dimethyl Benzene is particularly effective. The reaction of the present invention is normally carried out under atmospheric pressure. However, in certain circumstances, it can be confirmed that it is advantageous to carry out the reaction at a higher or lower pressure. In the formulas (1) and (2) Within the scope of the compound, when R! represents a halogen, it may be fluorine, bromine, iodine or, in particular, chlorine.

The Ri- and/or R2 groups of the Ci-Ciq group may be branched or unbranched such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, Third butyl, 2-ethylbutyl, n-pentyl, isopentyl, 1-methylpentyl, 1,3-dimethylbutyl, n-hexyl, 丨-methylhexyl, plus Heptyl, isoheptyl, 1,1,3,3-tetramethylbutyl, 1-methylheptyl, 3-methylheptyl, n-octyl, 2-ethylhexyl, U, 3_ Trimethylhexyl, tetramethylpentyl, n-nonyl or n-decyl. The CrCw alkyl esters of the compound of the formula (3) are correspondingly substituted.

The CrCH alkoxy group R1 may be branched or unbranched such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, second butoxy, isobutoxy 'T-butoxy, 2-ethylbutoxy, n-pentyloxy, isopentyloxy' 1-methylpentyloxy, 1,3-dimethylbutoxy, n-hexyloxy Base, 1- 7 The paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1298325 A7 ------- ---- V. Description of invention (t) Methylhexyloxy, n-Heptyloxy, isoheptyloxy, 1,1,3,3-tetramethylbutoxy, 1-methylheptyloxy, 3-methylheptyloxy, n-octyloxy, 2- Ethyl heptyloxy, 1,1,3-trimethylhexyloxy, 1,1,3,3-tetramethylpentyloxy, n-decyloxy or n-decyloxy. The aralkyl group R2 may be benzyl or phenethyl which may be substituted via a halogen, CrC1() alkyl or CrCioalkoxy group or, preferably, unsubstituted. The alkali metal or alkaline earth metal ruthenium may be selected from the group consisting of K, Na, Ca or Mg, but is preferably K or Na. The following examples further illustrate the invention but are not intended to be limiting of the invention: Example 1

25 g of N-methylpyrrolidone was placed in a reaction vessel and 82 g of 98% bisdiphenylene-4,4,-dicarboxylic acid was added with stirring, followed by the addition of 75 g of 99% 2-aminophenol. , 1 gram of boric acid and 30 grams of xylene. The device with the Dean and Stark water trap was evacuated and the vacuum was released under nitrogen. The light yellow suspension was heated to 195. (: and stirring at this temperature for 18 hours, during which time 23-25 ml of water and about 25 g of xylene were distilled off through a dehydrator. The reaction mixture was cooled to 20.0: and stirring was continued at this temperature for 1 hour. The yellow suspension was filtered and washed with 1 gram of N-methylpyrrolidone to give a 350 gram brown solution which was calibrated to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) - -------------------^-------- (Please read the notes on the back and fill out this page again) A7

1298325 V. Description of the invention (heart) Used as a solvent for further addition and then added three portions of 80 grams of water. The resulting filter cake was dried at 100 ° C under a vacuum of 50 mbar to yield 120 g of a yellow solid compound of formula (101) characterized by an extinction coefficient e of 71000 at a maximum UV absorption 値 X max 368 nm. Example 2 According to the method described in Example 1, but substituting 82 g of 98 ° / 〇 2- thiophenol for 2-aminophenol and 3 g of tetraisopropyl titanate for boronic acid, which can obtain 115 The compound of formula (102), which is a yellow solid, is characterized by having an extinction coefficient e of 62000 at a maximum UV absorption of maxXmax 375 nm and the following 1H-NMR data in D6-DMSO: 8·12, 4H, m; 8.00, 6H ,m ; 7·85,4H,m and 7·48, 4· 4Η,m ο (Please read the notes on the back and fill out this page) Example 3

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Following the procedure described in Example 1, but substituting 72 g of 99% 1,2-phenylenediamine for 2-aminophenol, it gave 110 g of a yellow solid of formula (103) characterized by a maximum UV absorption. The extinction coefficient e of 63000 at Xmax370nm and the following 1H-NMR data in D6-DMSO: 9 The paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1298325 V. Invention description (7) 13.0 , 2H, s; 8.22, 4H, d, j = 7 Hz; 7·80, 4H, d, j = 7 Hz; 7.68, 2H, d, j = 7 Hz; 7·54, 2H, d, j = 7 Hz;

200 g of N-methylpyrrolidone was placed in a reaction vessel and 99% thiophenol-2,5-dicarboxylic acid was added with stirring, followed by 72 g of 99% 2-aminophenol, 10 g of boric acid and 30 g of toluene. . The apparatus with the Dean and Stark water trap was evacuated and the vacuum was released under nitrogen. The light yellow suspension was heated to 185 ° C and stirred at this temperature for 12 hours, during which time 23-25 ml of water and about 25 g of toluene were distilled off through a water separator. The reaction mixture was cooled to 20 ° C and held at this temperature for 4: stirring for 1 hour. The yellow suspension was filtered and washed with 100 g of N-methylpyrrolidone to give 300 g of a brown solution which can be used as a solvent for further addition and then three portions of 80 g of water. The resulting filter cake was dried at 100 ° C under a vacuum of 50 mbar to yield 75 g of a yellow solid compound of formula (104) characterized by an extinction coefficient of 52000 and a D6-DMSO at a maximum UV absorption of maxXmax 372 nm. The following 1H-NMR data were available: 8·10, 2H, s; 7.82, 4H, m and 7.50, 4H, m. Example 5 10 This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 public interest) (Please read the note on the back and fill out this page) _ II II — — — · IIIIIIII . 1298325 A7 B7 V. Description of invention (3)

(105) (Please read the note on the back and then fill out this page) In accordance with the method described in Example 4, but replace 2-aminophenol with 11 g of 2-amino-4-t-butylphenol. Substituting boric acid with 2.2 g of isopropyl- orthotitanate and replacing toluene with 30 g of xylene gives 125 g of a yellow solid of formula (105) characterized by an extinction coefficient of 51,000 at a maximum UV absorption of 値Xmax 375 nm. e and a single 1.30 ppm in 1H-NMR under D6_DMSO 〇 Example 6 | (106) 200 g of N,N-dimethylacetamide was placed in a counter-container and added 35 g 98% with stirring Trans-maleic acid followed by 82 grams of 2-amino-4-methylphenol, 1 gram of citric acid and 30 grams of xylene. The device with the Dean and Stark water trap was evacuated and the vacuum was released under nitrogen. The light yellow suspension was heated to 16 Torr. (: and stirring at this temperature for a while, during which time 23-25 ml of water and about 25 g of xylene were distilled off through a dehydrator. The reaction mixture was cooled to 20 ° and stirring was continued at this temperature for 1 hour. The yellow suspension was washed with 1 gram of N,N-dimethylacetamide and then washed with three portions of 80 grams of water. The resulting filter cake was dried at 100 ° C '50 mbar vacuum to yield 85. The compound of formula (106), which is a yellow solid, is characterized by a maximum UV absorption of maxXmax 365 nm. 11 This paper scale applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) with an extinction coefficient e of 42000. Example 7

1298325 A7 ____B7__ V. INSTRUCTIONS (?) (107) 200 g of N-methylpyrrolidone is placed in a reaction vessel and 65 g of furan-2,5.dicarboxylic acid is added with stirring, followed by 72 grams of 99% 1,2-phenylenediamine and 1 gram of boric acid. The device with the Dean and Stark water trap was evacuated and the vacuum was released under nitrogen. The pale yellow suspension was heated to 175 ° C and stirred at this temperature for 12 hours, during which time 28 g of ethanol was distilled off under a weak vacuum. The resulting solution was cooled to 2 ° C and stirring was continued at this temperature for 1 hour. The yellow suspension was filtered and washed with 100 g of N-methylpyrrolidone to give 300 g of a brown solution which can be used as a solvent for further addition and three portions of 80 g of water were added. The resulting filter cake was dried under vacuum at 50 °C to give 95 g of a yellow solid solid compound of formula (107) characterized by an extinction coefficient e of 42000 at a maximum UV absorption of maxXmax 375 nm. This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) ------------------- Order --------- (please Read the notes on the back and fill out this page.)

Claims (1)

1298325 Sixth, the scope of application for patents 1, ~ a method for the preparation of the following compounds, Wherein y represents -〇-, -s- or -n(r2)-, R2 is hydrogen or (VC4 alkyl; Z represents 2,5-pyranyl '2,5-phenylthio' 4,4' - a homo- or a 1,2-ethylenyl residue and the Ri represents a chlorine or a C1-C4 group, characterized by an N-methylpyrrolidone or N , N-dimethylacetamide in the presence of an acidic catalyst and, optionally, in the presence of a second solvent capable of removing water from the reaction mixture, the compound of the formula Rrf / (2) ^YH is reacted with a dicarboxylic acid of the formula HOOC-Z-COOH (3) or an ester thereof, and γ, z and core are as defined above. 2. According to the method of claim 1 of the scope of the patent application, Wherein at least two moles of the compound of formula (2) are reacted with at least one mole of the formula (3) dicarboxylic acid or an ester thereof. 3. According to the method of claim 1, wherein formulas (2) and (3) The reaction of the compound is carried out in N-methylpyrrolidone. The method according to claim 1, wherein the acid catalyst is selected from the group consisting of boric acid, phosphoric acid, G-C4 orthoester titanium or tin derivative. In the group/group of the group. 1 ^Paper is applicable to China Home Standard (CNS) A4 Specification (210 X 297 mm) " (Please read the notes on the back, fill out this page > Order #· 1298325 B8 C8 D8, apply for patent scope 5, according to the fourth scope of the patent application scope The method wherein the acid catalyst is boric acid or Crq orthoester titanium. 6. The method according to claim 1, wherein the reaction of the compounds of the formulas (2) and (3) is in a temperature range of 100 and 7. According to the method of claim 1, wherein the reaction of the compounds of the formulas (2) and (3) is carried out at a temperature ranging between 150 and 200 ° C. 8. According to the scope of claim 1 The method wherein the second solvent capable of removing water from the reaction mixture is selected from the group consisting of toluene, xylenes and their isomeric mixtures and pyridine. (Please read the notes on the back first) On this page) MS·r·Binding-· This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm)