JPS59137475A - Manufacture of benzothiazole - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to the use of suitable cleavage groups.
) is reacted with a suitable amine benzene or nitrobenzene in the ortho position with a suitable thioamide or thioamide-forming system, provided that 1-European percent A O,0
No. 69,445 (Example 16) to eliminate the reaction of O-amine phenol with ammonium thiocyanate according to the formula [wherein R represents H, NH, or R7, R1 represents alkyl or aryl] 1~, and ring A may have other substituents].

A preferred variation of this method is to represent a group of the formula [wherein X is a halokene, 5OB3.050.R, formula (11)], and when L and Y are No2, scN is and 7 Y represents NO2 or NB2] is reacted in one of the possible tautomeric forms with a compound corresponding to the formula or a system producing these compounds. It is characterized in that in the case of the reaction with a preformed compound (2), the group X can also represent 511.

Suitable alkyl groups R1 representing the same or different substituents J7 and It is a saturated or unsaturated alkyl group, preferably having 1 to 6 carbon atoms (obviously at least 2 in the case of an unsaturated group). Methyl groups are particularly preferred.

Suitable aryl groups mentioned in any order may likewise be
Inert” substituents, such as C1-C4 alkyl, C1-
It is an aromatic carbocyclic or heterocyclic group which may be substituted with C4 alkoxy or activated salefxy/·logon.

Examples of suitable substituents for ring A are nolog/, R1, -0R
1, cN, -COR,, -CO2R,, C0N (RIL
, 5o311. So, R,, So,, Ni12.5o
2N(R1)2, NO2, CF3 or -n=N-aryl, where ``alkyl'' and ``aryl'' have the preferred meanings given above, and also appear preferred in the 5/7-positions. Strong electron-withdrawing substituents are preferred.

Furthermore, ring A may be fused with other rings, preferably 1-< aromatic.

"Halokene" can be understood to include chlorine or bromine.

Preferred compounds of the formula CF3, CN, -CO-7rukyl, -3O2-fulkyl, 1. -so□-phenyl, -co2-alkyl, -C
ON (7k Kyl) 2 Also indicates Fi ” 02N (alkyl) 2 1-1 However, both Z and Z2 do not represent hydrogen, and the alkyl group has 1 to 6 carbon atoms, 1 to 1, so l-
The phenyl group is C1゜Br, No2 or c, , c, AA
X represents chlorine, bromine, SE, S, CN or a group of formula ll1a, with the proviso that Y represents N02 or NH2, and O represents NO2, and Xl is SH or n=2 function ■1
When it is a group α, it also shows NR2] A sulfur-containing group X and an electron-withdrawing group Z1 and/or Z are particularly preferred.

Zl is CF3, 5O2CH3, 5O2C-12C
1,5o2C211,,SO□C,li, and especially NO
2 and Z2 represents CF3, NO2 or especially H L1X
Compounds of the formula (Oa) in which C1 represents C1 and Y represents NO2 are very particularly preferred.

Preferred compounds of formula (iv) are those in which R represents NH2, alkyl or aryl, the hydrocarbon group having the general and specific meanings given above. Suitable compounds of formula (IV) are therefore thioamides and especially thioureas.

Furthermore, the compound in which urea may be in its oxide form is preferably used as is (i.e., in combination with the previously formed compound).
-) or generated "in situ" from a suitable system to form the thioamide in the reaction mixture. An example of this type of "thioamide generator" is the formula NH4■5CN
A mixture of thiocyanates of R, -NBρ5csc:) in which O and R1 represent C1-C6 alkyl or optionally substituted phenyl, and compounds liberating 112S or B2S of the formula R, -CN or NjJ□CN. In the latter case, hydrogen sulfide is preferably present in an excess amount, where L<.

Although the compound of formula (IV) can be present in equimolar amounts with the compound of formula (1) in which Y is NH2, it must be used in excess with respect to the compound ([1) with Y=NO2]. Generally, a small excess of 5 to 10% of the vehicle volume is sufficient.

However, preferably 2 to IO1 for (II)
Particularly preferably 1 to 3 to 6 equivalents of (IV) are used.

Essentially, the reaction of (jl) with (IV) can advantageously be carried out in a relatively large excess of melt (IV) without diluent. I-In many cases, however, the reaction is more or less exothermic, so that it is expedient to carry out the reaction in the presence of a solvent that is inert under the reaction conditions, so that the heat generated can be better removed. can.

Particularly suitable solvents are those of organic compounds, such as high-boiling alcohols (in particular propatool, getanol and pentanol), glycol ethers (such as methyl, ethyl and butyl glycols and diethylene glycol no methyl ether), cyclic amides (such as y-methylpyrrolidone and caprolactam), ketones such as soethylketone and especially tetrahedral; lotiophene 1,1-soxide.

water and aqueous 2, if appropriate in the presence of a phase transfer catalyst.
Phase systems (eg toluene/water) are also suitable in conjunction with the solvent.

On the other hand, solvents with alkali/acid groups are not suitable because they participate in the reaction under certain conditions.

Generally the reaction is carried out at 60 to 250°C, preferably 70 to 20°C.
It is carried out at a temperature of 0°C, and particularly preferably from 70 to 150°C.

In contrast to the conventional method, a practical method is to produce compound (IV) or it from compound (b) without excessively exceeding the reaction temperature found to be appropriate in preliminary experiments. Introducing the system into suspension or solution1. This will be done to your advantage. If appropriate, the reaction vessel may be cooled during this period.

Bases (e.g. tert-amines or N-heterocycles)
The addition of 1- or j- is advantageous.

The end of the reaction or complete conversion is best detected by thin layer chromatography.

The reaction products, many of which are known, are used for various industrial products.
It is a useful starting material. The azo dye (German patent no. 6)
39.727), sensitizers (German patent no. 710.748)
), metal complex dye (Nagochi Publication Patent No. 4848.622)
), herbicides (U.S. Pat. No. 2,756,135) and polymethine with a wide range of applications (see, 1iouken-W
``M'ethode?Lder Orga'' by Eyl
Nischen Chemie”, 4th edition, Volume V/l
1. Pointed out the adaptability to the manufacturing of
There must be.

The novel method uses the known 11wgershoff synthesis (R
.

C1Elderfield, “1ieterocyc
lic Compow-nd811X Vol. 5, pages 581 onwards, John Wiley & 5ons, N
ew York 1957, and Narrow Mouth Publication Patent No. 2.
No. 631.163), the method is distinguished by the fact that it is not particularly roundabout. The reason for this is that 2-aminobenzothiazole is prepared in one step from industrially readily available starting materials such as O-chloronitrobenzene derivatives. On the other hand, in Hugersho ff's method, a suitable phenylthiourea is first prepared from an aniline derivative and then cyclized using an oxidizing agent in a second step to obtain 2-
It is necessary to produce aminobenzothiazole.

Another disadvantage of the Hugershoff synthesis is that in the case of meta-substituted anilines, the product is not homogeneous and is considered to be a mixture of 5- and 7-substituted 2-7 minobenzothiazoles (see Oral Publication Patent No. 2.60
'2,173 = U.S. Pat. No. 4,054,379). Additionally, the ffugershoff process is limited by the inability to easily prepare phenylthioureas with strongly electrohostile substituents. In some cases it is necessary to take an indirect route via suitable acylphenylthioureas (Japanese Published Patent No. 4602.173).

Similar drawbacks apply to the oxidative reaction of aniline with thiocyanate (see Die pnαrmαzie).

32.195. (1977)).

Example 1 Production of 2-7my-s-nitrobenzothiazole Sulfolane (tetrahydrothiophene 1,1-dioxide)
2,4-sonitrochlorobenzene in 50d 10.13
A suspension of F and thiourea 15.25'
The mixture was stirred at 0° C. for 12 hours. After cooling, mix 80% of mixture J with water.
0mg and stir completely 1-1 Suction filtration of solid 1~, Wash with water 1
~is. After drying, yellow powder 11.2f containing 69.59% (80 parts of the theoretical amount) of 2-amino-5-nitrobenzothiazole was obtained according to 1jpLc (high performance liquid chromatography) analysis.

By recrystallization from methylformamide, melting point is 30
7°C (decomposition) (Zhur, Obsche
iKhim, 30.1363-6 (1960), melting point 308-309°C (decomposition)).

Example 2 Production of 2-amino-5-nitrobenzothiazole 10.1 2.4-dnitrochlorpenzel in 50 ml of Hiridun
3 ft' and thiourea 15. The solution of '2f was boiled for 3 hours under reflux and condensation with stirring. After cooling, the mixture is thoroughly stirred with 500 ml of water, the solid is filtered with suction, washed with water and dried. 2-Amino-5-nitropencinazole 11 with a purity of 66 by HpLC analysis
．． 6F (f#U, corresponding to a yield of 785% of theory) was obtained.

Example 3 Preparation of 2-amino-5-nitrobenzothiazole Sulfolane 257! Medium 2,4-dunitrochlorobenzene s, o
A suspension of 6f/0'7 ammonium thiocyanate 7.62 was heated to 150°C with stirring, and at this temperature 1.
It lasted for 5 hours. The product was poured into 300 m of water and the solid was washed with water under suction. After drying, crude 2-amino-5-
6.572 nitrobenzothiazole was obtained. Identification was performed by comparing with a standard sample by TLC (thin layer chromatography).

Example 4 Preparation of 2-amino-5-nitrobenzothiazole In a solution of 7.62 ml of thiourea in 50 m7 of methylformamide
, 11.71 r of 4-sonitrophenylthiocyanate were added in portions over 15 minutes at 150°C. The mixture was heated at 150'C for 2 hours, the product was poured into 500ml of water, and the solids were washed with water by suction. 2-Amino-5-nitrobenzothiazole 112 was obtained. This identification was performed by comparing with a standard sample by TLC.

Example 5 Preparation of 2-amino-5-nitrobenzothiazole A solution of 10 parts of 2,4-dunitrothiophenol and 7.62 parts of thiourea in 50 mg of dimethylformamide was heated to 120°C for 3 hours.
heated for an hour. The mixture was diluted with 300ml of water, and the solids were sucked out and washed with water. J-da2-amino-5-nitrobenzothiazole 732, identified by comparison 1 to standard sample and TLC, was obtained.

Example 6 Preparation of 2-amino-5-nitrobenzothiazole 2.4.2',4'-tetranitrosophenyl sulfide 5972 and thiourea 4 in 40 ml of methylformamide
．． The 56 f/ solution was stirred at 120'C for 3 hours. Pour the mixture into 300 ml of water. put it inside and suck out the solids] ~,
Wash with water 1-. 4.5y of crude 2-amino-5-nitrobenzothiazole with a melting point of 290-30°C (decomposed) was obtained.

Example 7 Preparation of 2-amino-5-nitrobenzothiazole 2,'4. ．． Add 2',4'-tetranitrosophenyl sulfide 9152 at 120°C for 15 minutes;
~, stirring was continued at this temperature for 2 hours. Mixture with water 300%
After dilution with Biao, the solid was suctioned and washed with water. Melting point 2
76 g of crude 2-amino-5-nitrobenzothiazole was obtained at 90-300°C (decomposed).

Example 8 Preparation of 2-amino-5-nitrobenzothiazole A solution of 8.63 r of 2-chloro-5-nitroaniline and 9.9 g of sodium sulfide trihydrate in 80 mA of butyl glycol was stirred at 80°C for 30 minutes. . Concentrated sulfuric acid 4.16 m+
! After the addition of thiourea 767 was added to the 2-amino-4-nitrophenol and the mixture was stirred at 120°C for 3 hours.
~is. The reaction mixture was poured into 400 m of water and 5 m of methanol, and the solid was suctioned and washed with water. Identified by comparing with standard sample and 7'LC
-Amino-5-nitrobenzothiazole 547 was obtained.

Example 9 Preparation of 2-amino-5-nitrobenzothiazole 2,2'-noamino-4,4'-dunitroduphenylsosulfide (E'odgson and Dod
Gson, J. Chem, Soc, 1948.
870) 6.767 and thiourea 6.08 f 130
Stir at °C for 3 hours. The mixture was diluted with 300 πl of water, and the solid was suctioned separately (1) and washed with water. Standard material and 7'
Identification by comparison with LC gave crude 2-amino-5-nitrobenzothiazole 7.21i+.

Example 10 Preparation of 2-methyl-5-nitrobenzothiazole 2.4-sonitrochlorobenzene in 50 mA of sulfolane 10.
A suspension of 139 and thioacetamide 151 was heated to ioo°C.
Heat to 1~ and stir at this temperature for 1 hour. After cooling,
The mixture was clarified. Add 200ml of water to this tear fluid1
~Ta. The solid was suctioned 1~1, washed with water 1/1, and dried. Yield: 6.02 F homogeneous material by thin layer chromatography.

Recrystallization from ethanol gave a melting point of 133°C (J, Chem.

Soc, perkin Trans, IXl
According to 973.356-359, melting point 135-137
℃).

Example 11 Production of 2-amino-5-nitro-7-trifluoromethylbenzothiazole To a solution of 152 g of thiourea in 50 i of sulfolane, 2-
Chlor-3,5-dinitrobenzotrifluoride l3
．． 5 Slowly add y while stirring at 100'C 1-
Ta. The mixture was stirred for a further 25 hours at 1 tlO 0 C, cooled to 12 ml, the mixture was vacuumed and the dried residue was washed with 50 ml of carbon disulfide.
nrl, and co-inclined with thorough stirring. Solid by suction furnace; 7
, uniform thickness by chromatography and 303-307
A substance with a melting point of 7.52 °C (decomposed) was obtained. Recrystallization wave from pyrinone/water (3/l), melting point 315-31
The temperature was 6°C (decomposition). m,, 263゜Example 12 Preparation of 2-amino-5-trifluoromethyl-7-nitrobenzothiazole 4-chloro-3,5-sonitrobenzotrifluoride 6757 was added to a solution of thiourea 767 in sulfolane 250 Biao.
Slowly introduce the mixture at 100°C while stirring. The mixture was stirred for an additional hour at 100°C. After cooling, the precipitate is vacuumed and separated and dried.

Crude 2-amino-5-to, melting point 254-256°C (decomposed)! J Fluoromethyl-7-nitropenzothiazole 35
I got 72. Recrystallization from pyrinone/water (3/l) raises the melting point to 262-263°C. M words: 2
From the filtrate of the 63° crude product, an additional 287 t could be precipitated by adding 500 mJ of water.

Example 13 Preparation of 2-amino-5-ethanesulfonylbenzothiazole A suspension of 4-chloro-3-nitrophenylsulfone 1287 and thiourea 1527 in 50 r/ml of sulfolane was prepared by
It was heated to 20°C and kept at this temperature for 15 hours. The mixture was poured into 600 ml of water, and the solids were suctioned and washed separately with water. Colorless 2-amino-5-ethanesulfonylbenzothiazole to6r was added. λ max −
To 234tz m (CH3C8') m luck: 24
2゜Example 14 Preparation of 2-amino-5-benzenesulfonylbenzothiazole In a solution of 1522 thiourea in 50 ml of sulfolane, 4
-Chlor-3 to 14.92 nitroduphenylsulfone were introduced at 150 DEG C. and kept at this temperature for 1 hour.

The mixture was poured into 500 m of water and the solids were vacuumed off and washed with water. The dried product was stirred vigorously with 50 ml of carbon disulfide. The solids are sucked up and separated into coarse 2 to amino 5
-benzenesulfonylbenzothiazole 15.547 was obtained. mkichi: 290. Melting point = 278-280℃ decomposition (from trimethylformamide/water (l/1'), λmax
= 245 nm (CJi3CN).

Example 15 Preparation of 2-amino-5-chloromethanesulfonylbenzothiazole 13.8% of chloromethyl 4-chloro-3-nitrophenylsulfone is added to a solution of 1527% of thiourea in 50% of sulfolane.
3f/ was introduced at 150'c and kept at this temperature for 1 hour. By treating as in Example 14, 2-amino-5-chloromethanesulfonylbenzothiazole IOS
'I got it. m kichi: 262, λmaz-233n'I
n (CHsCN).

Example 16 Preparation of 2-aminobenzothiazole A suspension of sulfolane 50mA 2.2'-dunitrophenylsosulfide 9.54/ and thiourea 1527
Stir at 0°C for 4 hours and then at 150°C for 4 hours. The mixture was clarified and the furnace liquor was poured into 250 d of water. 1. Recrystallize the initially oily precipitate from ethanol. Ta. 0.547 of 2-aminobenzothiazole was obtained, which was identified by comparison with a standard substance by 1''LC.

Patent applicant: Bayer Akchenkeselshaft

Claims (1)

[Scope of Claims] 1. A benzo compound of the formula [wherein II', NH2 or R1, R8 represents alkyl or aryl, and ring A may have other substituents] In the production of thiazoles, the reaction of a suitable amine benzene or nitrobenzene having a suitable cleavage group in the ortho position with a thioamide or a thioamide-forming system, excluding the reaction of minophenol (1-0-7) with ammonium thiocibnate. A method for producing the benzothiazole. Formula 2 [In the formula, X ij HCI If :y, 5OE3, O
S O, R1, formula (Ill), where 1y ""' represents a group of 1 or 2, 1-11 to 1-11, or when Y is NO2, represents SCN, I-1, and Y represents No2 or N-12] are reacted with compounds corresponding to the formula in one of the possible tautomeric forms or with systems forming these compounds, provided that in the case of reaction with a preformed metal compound of the formula 2. A method as claimed in claim 1, in which the group X can also represent SH. 3. A preformed compound of formula (IV) is prepared in which R is SH
2, C1-C, alkyl, or optionally C1-C. A process according to claim 1, in which a compound of this formula represents alkyl, N02, CF3, -5O2-C, ~C, alkyl, halokene or phenyl substituted with CN and 1-. 4. Nitriles of formula R, -CN or HNCN and 112
A method according to claim 1, in which a mixture of compounds liberating S or H2S is used in combination with a compound of formula (IV). 5, Ni14■SCN○ or R, -Ni13■SCN
○ is used with the compound of formula (IV) from 1 to 1, provided that 1. R,
is C1~C67 Lucil or any time CIX BrXNo2
or phenyl substituted with C7-C4 alkoxy. 6. As a compound of formula (II), formula IIa [wherein Zl and Z2 are hydrogen, C1, Dr, 'NO2,
CF3, CN, -Co-furkyl, -5O2-alkyl, -5O2-phenyl, -CO2-alkyl, -CON
(alkyl)2 or -5O2N(alkyl)2 (~
, provided that both 1-Z1 and Z2 do not represent hydrogen, the alkyl group has 1 to 6 carbon atoms, and the phenyl group fi
Cl, BrX1V02 or 1d-C, ~C, may be substituted with flukoxy; , represents No2, 1-1 and also represents N112 when Xl is Slf or a group of the formula ■α of n-2. 7. As a compound of 2B, the formula lea [wherein, Zl is CF3.5O2CH3,5o2CB2C
1,5O2C2)15, So2C6M, and NO2, and Z2 is 11. CF or NO2, X is ct
and Y represents NO2. 8. The method according to any one of claims 1.6 and 7, wherein thiourea is used in combination with a compound of formula (IV). 9. The method according to claim 1, wherein the compound of formula (lv') is used in an excess amount of 5 to 10% relative to 1 equivalent of the compound of formula (b). 10. 3 to 6 equivalents of the compound of formula (IV) to the compound of formula (II
2. The method according to claim 1, wherein the method is reacted with 1 equivalent of a compound of