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IE54442B1 - 2-aminobenzamides - Google Patents

2-aminobenzamides

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Publication number
IE54442B1
IE54442B1 IE449/87A IE44987A IE54442B1 IE 54442 B1 IE54442 B1 IE 54442B1 IE 449/87 A IE449/87 A IE 449/87A IE 44987 A IE44987 A IE 44987A IE 54442 B1 IE54442 B1 IE 54442B1
Authority
IE
Ireland
Prior art keywords
tetrazol
water
methyl
benzamide
solution
Prior art date
Application number
IE449/87A
Other versions
IE870449L (en
Original Assignee
Dow Chemical Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US06/340,577 external-priority patent/US4419357A/en
Application filed by Dow Chemical Co filed Critical Dow Chemical Co
Publication of IE870449L publication Critical patent/IE870449L/en
Publication of IE54442B1 publication Critical patent/IE54442B1/en

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  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

The present invention relates to 2-aminobenzamides which are of utility as intermediates in the synthesis of the 3-(lH-tetrazol-5-yl)-4(3H)-quinazolinones described and claimed in Patent Specification No. 544 41 Novel compounds of the present invention have the formula wherein R* is hydrogen, methyl, methoxy, halogen or 4,5-methylenedioxy. R' is preferably methyl.
Compounds of the invention may be obtained by catalytic hydrogenation of an alkaline solution of the corresponding 2-nitrobenzamide. The preferred catalyst is 5% Pd/C although similar catalysts, such as Pt/C, can also be used. The starting tetrazole is preferably dissolved in aqueous IN sodium hydroxide solution; if necessary, this can be diluted with ethanol or additional water.
The 2-nitrobenzamide is obtained by reaction of the appropriate 2-nitrobenzoyl chloride with -aminotetrazole, and the acid chloride is obtained from the corresponding carboxylic acid, all using standard procedures.
The following Examples illustrate how compounds of the invention and their precursors may be prepared.
S4442 EXAMPLE 1 To a slurry of 78 g of 4,5-methylenedioxy-2-nitrobenzaldehyde and 1.5 liter of water there was added a solution of 90 g of potassium permanganate in 1.5 liter of water over a period of 45 minutes. The mixture was then stirred at 70-80°C for an additional hour and then made alkaline with 400 ml of aqueous 10% potassium hydroxide. The mixture was filtered while hot to remove the precipitate which was washed with 2 portions of hot water. The filtrate was cooled for 16 hours and the solid which formed was separated by filtration to give recovered starting material. The new filtrate was acidified with concentrated hydrochloric acid and allowed to stand for 3 hours. The yellow solid which formed was separated by filtration to give crude product. The filtrate obtained was extracted with 4 portions of ethyl acetate and the combined extracts were dried over sodiuta sulfate and added to a solution of the previously obtained crude product in ethyl acetate. The ethyl acetate solution was concen20 trated, the resulting solid was slurried with chloroform, separated by filtration and dried to give 4,5-methylenedioxy-2-nitrobenzoic acid melting at about 160-163°C.
EXAMPLE 2 A mixture of 25 g of 2-methyl-6-nitrobenzoic acid and 28.7 g of phosphorus pentachloride in 300 ml of cyclohexane was heated at reflux for 1 hour. The solution was concentrated and the residue was twice treated with chloroform and concentrated again to remove readily volatile materials and leave, as a residue, 2-methyl-6-nitrobenzoyl chloride as an oil.
To a warm solution of 28 g of 5-aminotetrazole monohydrate in 300 ml of tetrahydrofuran and 15 ml of water was added 26.7 g of 2-methyl-6-nitrobenzoyl chloride in 50 ml of tetrahydrofuran. The solution was allowed to stand for 16 hours, the solvent was evaporated and the residue was treated with water. The solid obtained was separated by filtration, slurried with ether and again separated by 44 4 2 filtration to give 2-methyl-6-nitro-N-(lH-tetcazol-S-yl)benzamide melting at about 23Q-232°C.
EXAMPLE 3 Using the appropriate reactants, the procedure as described in Example 2 was repeated to give the corresponding products as follows: The reaction of 36.2 g of 5-methyl-2-nitrobenzoic acid and 41.6 g of phosphorus pentachloride in 150 ml of toluene gave a crude product which was treated with meth10 ylene chloride to give 5-methyl-2-nitrobenzoyl chloride as an oil. When 30 g of this acid chloride in 50 ml of tetrahydrofuran was added to a warm solution of 30.9 g of -aminotetrazole monohydrate in 600 ml of tetrahydcofuran and 30 ml of water, a precipitate formed quickly. This was allowed to stand for 1 hour, the white solid was separated by filtration, washed with water and air dried to give 5-methyl-2-nitro-N-(lH-tetrazol-5-vl)benzamide melting at about 278-279°C.
The reaction of 50 g of 3-methyl-2-nitrobenzoic acid and 57.5 g of phosphorus pentachloride in 300 ml of cyclohexane gave, after treatment of the crude product with methylene chloride, 3-methyl-2-nitrobenzoyl chloride melting at about 81-82°C. A solution of 53.1 g of this acid chloride and 50 ml of t^trahydrofuran was added to a warm solution of 55 g of 5-aminotetrazole monohydrate in 500 ml of tetrahydrofuran and 20 ml of water. The reaction was exothermic, a white precipitate formed and the mixture was allowed to stand for 4 hours. It was then diluted with water, the white precipitate was separated by filtration, washed with water and air dried to give 3-methyl-2-nitroN-(lH-tetrazol-5-yl)benzamide melting at about 262-263°C, with decomposition, after recrystaliization from a mixture of dimethylformamide and water.
Reaction of 100 g of 5-chloro-2-nitrobenzoie acid and 103.3 g of phosphorus pentachloride in 400 ml of cyclohexane at reflux for 80 minutes followed by treatment of the crude product 3 times with carbon tetrachloride gave -chloro-2-nitrobenzoyl chloride. A solution of the acid chloride in 50 ml of tetrahydrofuran was added to a warm solution of 91.3 g of 5-aminotetrazole monohydrate in 500 ml of tetrahydrofuran and 20 ml of water. A precipitate formed, and the mixture was allowed to stand for 4 hours.
It was then diluted with water and the solid was separated by filtration and air dried to give 5-chloro-2-nitro-N(lH-tetrazol-5-yl)benzamide melting at about 268-269°C, after recrystallization from dimethylformamide.
Reaction of 30 g of 3-methoxy-2-nitrobenzoic acid and 31.6 g of phosphorus pentachloride in 400 ml of methylene chloride at reflux for 2 hours followed-by treatment of the crude product obtained with toluene 3 times gave 3methoxy-2-nitrobenzoyl chloride as a solid. A solution of 30 g of this acid chloride in 50 ml of tetrahydrofuran was added to a solution of 28.7 g of 5-aminotetrazole monohydrate in 300 ml of tetrahydrofuran and 15 ml of water.
•A white precipitate appeared immediately but the mixture was allowed to stand for 3 hours. It was then diluted with water and the white solid was separated by filtration and air dried to give 3-methoxy-2-nitro-N-(lH-tetrazol-5yl)benzamide melting at about 271°C after recrystallization from dimethylformamide.
Reaction of 31.7 g of 4,5-methylenedioxy-2-nitrobenzoic acid and 31.2 g of phosphorus pentachloride in 250 ml of cyclohexane at reflux for 30 minutes followed by treatment of the crude oil twice with carbon tetrachloride gave 4,5-methylenedioxy-2-nitrobenzoyl chloride. The acid chloride was dissolved in 50 ml of tetrahydrofuran and added to a warm solution of 30.9 g of 5-aminotetrazole monohydrate in 750 ml of tetrahydrofuran and 30 ml of water. The solution was stirred for 30 minutes and then diluted with 3 liters of water. The solid which formed 4.4 4 ϋ was separated by filtration and dried to give 4,5-methylenedioxy-2-nitro-N-(lH-tetrazol-5-yl)benzamide melting at about 279°C after recrystallization from a mixture of dimethylformamide and water.
To a solution of 10.3 g of 5-aminotetrazole monohydrate in 300 ml of tetrahydrofuran and 15 ml of water was added 9.3 g of 2-nitrobenzoyl chloride. The solution was allowed to stand for 30 minutes before it was diluted with 200 ml of water and stored in a refrigerator for 72 hours.
The solid which formed was separated by filtration to’ give 2-nitro-N-(lH-tetrazol-5-yl)benzamide melting at about 272-273°C with decomposition.
EXAMPLE 4 A solution was prepared from 7.5 g of 2-methyl-615 nitro-N-(lH-tetrazol-S-yl)benzamide in 100 ml of aqueous IN sodium hydroxide. A 0.5-g quantity of 5% Pd/C was added and the mixture was hydrogenated in a Parr apparatus at 3.3 atmospheres until uptake of hydrogen stopped (75 minutes). The catalyst was removed by filtration and the filtrate was treated with 100 ml of aqueous IN hydrochloric acid. The white solid which formed was separated by filtration and air dried to give 2-amino-6-methyl-N(lH-tetrazol-5-yl)benzamide melting at about 248°C with decomposition.
EXAMPLE 5 Using the appropriate reactants, the procedure as described in Example 4 was repeated to give the appropriate corresponding products as follows: Hydrogenation of 24.8 g of 5-methyl-2-nitro-N-(lH30 tetrazol-5-yl)benzamide in 125 ml of aqueous IN sodium hydroxide and 100 ml of ethanol gave 2-amino-5-methyl-N(lH-tetrazol-5-yl)benzamide melting at about 245-24G°C after recrystallization from ethanol.
Hydrogenation of 3-raethyl-2-nitro-N-(lH-tetrazol-5yl)benzamide gave 2-amino-3-methyl-N-(lH-tetrazol-5-yl)benzamide melting at about 258-259°C (dec) after recrystallization from a mixture of dimethylformamide and me5 thanol.
Hydrogenation of 5-chloro-2-nitro-N-(lH-tetrazol-5yl)benzamide using 0.5 g of 5% Pt/C catalyst gave 2amino-5-chloro-N-(lH-tetrazol-5-yl)benzamide melting at about 255°C after recrystallization from dimethylforma10 mide.
Hydrogenation of 3-methoxy-2-nitro-N-(lH-tetrazol-5yl)benzamide gave 2-amino-3-methoxy-N-(lH-tetrazol-5yl)benzamide melting at about 268-269°C after recrystallization from a mixture of dimethylformamide and water.
Hydrogenation of 10 g of 4,5-methylenedioxy-2-nitroN-(lH-tetrazol-5-yl)benzamide in 40 ml of aqueous IN sodium hydroxide solution and 160 ml of water and using 1 g of 10% Pd/C gave 2-araino-4,5-methylenedioxy-N-(lH-tetrazol-5-yl)benzamide as brown needles melting at about 255°C (dec) after recrystallization from a mixture of dimethylformamide and water.
Hydrogenation of 19 g of 2-nitro-N-(lH-tetrazol-5yl)benzamide in 100 ml of aqueous IN sodium hydroxide solution and 100 ml of ethanol using 0.5 g of 5% Pd/C catalyst and 2 atmospheres pressure gave 2-amino-N-(1Htetrazol-5-yl)benzamide melting at about 253-254°C.

Claims (8)

1. A compound of the formula wherein R’ is hydrogen, methyl, methoxy, halogen or 5 4,5-methylenedioxy.
2. A compound as claimed in claim 1, wherein R’ is methyl.
3. 2-Amino-N-(lH-tetrazol-5-yl)benzamide.
4. 2-Amino-
5. -methyl-N-(lH-tetrazol-5-yl)benzamide. 10 5. 2-Amino-4,5-methylenedioxy-N-(lH-tetrazol-5-yl)benzamide.
6. A compound of the formula given and defined in claim 1, which is any one of those specifically hereinbefore mentioned. 15
7. A process for preparing a compound of the formula given and defined in claim 1, substantially as hereinbefore described with particular reference to the accompanying Examples.
8. A compound of the formula given and defined in 20 claim 1, whenever prepared by a process claimed in claim 7.
IE449/87A 1982-01-18 1983-01-17 2-aminobenzamides IE54442B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US06/340,577 US4419357A (en) 1982-01-18 1982-01-18 3-(1H-Tetrazol-5-yl)-4(3H)-quinazolinones
IE78/83A IE54441B1 (en) 1982-01-18 1983-01-17 3-(1h-tetrazol-5-yl)-4(3h)-quinazolinones

Publications (2)

Publication Number Publication Date
IE870449L IE870449L (en) 1983-07-18
IE54442B1 true IE54442B1 (en) 1989-10-11

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IE449/87A IE54442B1 (en) 1982-01-18 1983-01-17 2-aminobenzamides

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IE (1) IE54442B1 (en)

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IE870449L (en) 1983-07-18

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