US3025303A - Certain nitrofuryl, thiadiazolyl amines - Google Patents

Certain nitrofuryl, thiadiazolyl amines Download PDF

Info

Publication number
US3025303A
US3025303A US763464A US76346458A US3025303A US 3025303 A US3025303 A US 3025303A US 763464 A US763464 A US 763464A US 76346458 A US76346458 A US 76346458A US 3025303 A US3025303 A US 3025303A
Authority
US
United States
Prior art keywords
nitrofuryl
thiadiazole
water
recrystallization
ethanol
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
US763464A
Inventor
Ifversen Else Norgaard
Rubinstein Kurt
Kurt Tyko Johannes Skagius
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Health AB
Original Assignee
Pharmacia AB
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
Application filed by Pharmacia AB filed Critical Pharmacia AB
Application granted granted Critical
Publication of US3025303A publication Critical patent/US3025303A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • A is selected from the group consisting of NH and substituted NH -groups containing substituents having from 1 to 8 carbon atoms, for example alkyl radicals such as methyl, ethyl, n propyl, isopropyl, n-bu-ty l, isobutyl or allyl, a substituted alkyl such as carboxy methyl, aryl radicals such as phenyl, aralkyl radicals such as benzy-l or phenethyl, alicyclic groups such as cyclohexyl, heterocyclic groups such as pyridyl.
  • the amino group may consist of a secondary amino group" having such a substituent.
  • novel compounds according to the invention have proved to possess surprisingly strong antibacterial activity and at the same time a remarkably low toxicity.
  • the invention also includes a process for producing the described compounds, which comprises treating S-nitrofurfuralthiosemicarbazones with oxidizing agents causing an oxidative ring closure of the semicarbazone with formation of the corresponding thiadiazole compounds.
  • reaction taking place may be illustrated by the following reaction formula:
  • a suitable oxidizing agents for this process may be mentioned salts of metals which occur in several oxidation stages, especially ferric salts, such as ferric chloride, ferric ammonium sulfate, potassium ferric sulfate, potassium ferric cyanide, sodium ferric cyanide, potassium ferric oxalate, sodium ferric oxalate, ferric ammonium citrate, ferric nitrate, ferric phosphate, ferric formate, ferric acetate and feric benzo ate.
  • ferric salts such as ferric chloride, ferric ammonium sulfate, potassium ferric sulfate, potassium ferric cyanide, sodium ferric cyanide, potassium ferric oxalate, sodium ferric oxalate, ferric ammonium citrate, ferric nitrate, ferric phosphate, ferric formate, ferric acetate and feric benzo ate.
  • the oxidizing reaction is preferably carried out by treating the compound to be oxidized in aqueous suspension with the oxidizing agent, suitably at elevated temperature, for example 60-90 C.
  • the oxidation can also be carried out electrolytically.
  • novel compounds accord ing to the invention possess very strong antibacterial activity and it has been found that said activity in certain cases is practically independent of the kind of the substituents attached to the nitrogen atom in the amino group A. This is shown more in detail in the tables below.
  • strains of the geni Salmonella and Shigella As examples of other micro organisms on which the compounds in question have proved to possess a strong growth inhibiting effect may be mentioned strains of the geni Salmonella and Shigella, bacetria of coliand streptococcus types, Haemophilus influenzae, Trichomonas vaginalis and Trichophyton.
  • the substance No. 1 i.e. the compound according to the invention, has a bacteriostatic effect of a very much higher order of magnitude than the substances Nos. 2 and 3.
  • nitrofurylthiadiazole compounds are 5-amino-2-(5- nitrofuryl) 1,3,4-thiadiazole, 5-methylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole, 5-ethylamino 2 (5-nitrofuryl)- 1,3,4-thiadiazole, 5-allylamino 2 (5-nitrofuryl)-1,3,4- thiadiazole, 5 benzylamino 2 (5 nitrofuryl)-1,3,4- thiadiazole, and further also 5-cyclohexylamino-2-(5- nitrofuryl)-1,3,4-thiadiazole and 5-phenylamino-2-(5-nitrofuryl) l ,3 ,4-thiadiazole.
  • Example I -5 -Amino-2-( 5 -N itrofuryl ,3,4-Thiadiazole 164 g. of 5-nitro-2-furfuralthiosemicarbazone is suspended in 511 ml. water and 765 ml. of 50% ferric chloride solution is added thereto. The mixture is heated to 6090 C. for 45 minutes while stirring. The raw reaction product so obtained is recrystallized twice from diluted dimethylformamide. On cooling the solution, yellow crystals crystallize out which melt at 270-271 C. with decomposition, yield 94 g. (57%).
  • a porous clay cell having a volume of about 200 ml.
  • diluted sulphuric acid is introduced and a cylinder-shaped cathode made from a sheet of copper, for example, is inserted therein.
  • Example 4 .5 -A mino-Z- (5 -N itrofuryl -1 ,3 ,4-thiadiaz0le 6.5 g. of 5-nitro-2-furfuralthiosemicarbazone and 30 g. of ferric ammonium sulfate are mixed with 100 ml. water and heated on water bath for about 1 hour while stirring. The precipitate which is thus formed is filtered off and dried. Weight 5.1 g. After recrystallization from dintethyl sulfoxide 4.0 g. of 5-arnino-2-(5-nitrofuryl)- 1,3,4-thiadiazole is obtained which corresponds to a yield of 63%. M.P. 270-272 C. with decomposition.
  • Example 5 -5-A min0-2-(5 -N itrofuryl ,3,4-Tl1iadiazole 4.2 g. of 5-nitro-2-furfuralthiosemicarbazone and 20 g. of potassium ferric cyanide in ml. water are heated on water bath for about 1 hour. The raw product so obtained is filtered off and dried and leaked with concentrated cold formic acid and filtered. The filtrate is diluted with water and hereby yellow crystals of 5-amino- 2-(5-nitrofuryl)-l,3,4-thiadiazole are formed which after drying weigh 2.4 g., corresponding to a yield of 57%. The compound is decomposed at 270-272 C.
  • Example 6 .5 -Ethylam ino-Z- 5 -N itrofuryl -1 ,3 ,4 T hiadiazole 24.2 g. of l-(5-nitrofurfural)-4-ethylthiosemicarbazone are treated with 100 ml. of 50% ferric chloride solution and 100 ml. water as described in Example 3. After recrystallization from ethanol-dioxane 13.7 g. (57%) of 5-ethylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole are obtained in the form of yellowish brown needles, M.P. 219- 221.5 C.
  • Example 9.5 -N -Buty laminO-Z- 5 -N itrofuryl 1,3,4-Thiadiaz0le 27 g. of I-(S-nitrofurfural)-4-n-butylthiosemicarbazide are treated with 100 ml. of 50% FeCl -solution and 100 ml. water as described in Example 3. After recrystallization from ethanol-dioxane 15.7 g. (58%) of S-n-butylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole in the form of yellow needles are obtained. M.P. 186187 C.
  • Example 1 I .5 -N -H exy IaminO-Z- 5 -N itrofuryl 1 ,3,4- Th iadiazole 11.9 g. of 1-(S-nitrofurfural)-4-n-hexylthiosemicarbazone are heated with 40 ml. of 50% FeCl -solution and 40 ml. water in the manner described in Example 3. After recrystallization from ethanol 5.8 g. (49%) of S-n-hexylamino-2-(5-nitrofuryl)-l,3,4-thiadiazole in the form of yellow crystals are obtained. M.P. 162.5163.5 C.
  • Example 13.5-Carboxymethylamino-Z-(S-Nitrofuryl) 1,3,4-Thiadiazle 2.5 g. of I-(S-nitrofurfural)-4-carbethoxymethylthiosemicarbazone are treated with 10 ml. of 50% FeCl solution and 10 ml. water in the manner described in Example 3. After recrystallization from ethanol 2.0 g. of -carbethoxymethylamino-2-nitrofuryl-1,3,4-thiadiazole in the form of yellow scales, M.P. l72.5-174 C. are obtained.
  • Example 14.5- (Z-Methoxyethylamino) -2-(5-Nitr0- furyl) ,3,4-Thiadiaz0le 4.1 g. of 1-(S-nitrofurfural)-4-(2-methoxyethyl)-thiosemicarbazone are heated with 15 ml. of 50% FeCl solution and 50 ml. water as described in Example 3. After recrystallization from ethanol 3.0 g. (74%) of 5-(2-methoxyethylamino)-2-(5 nitrofuryl) 1,3,4 thiadiazole in the form of yellow needles ar obtained. M.P. 169-171 C.
  • Example 15.-5-Benzylamin0-2-(5-Nitrofuryl)- 1,3,4-Thiadiaz0le 15.2 g. of 1-(5-nitrofurfural)-4-benzylthiosemicarbazone are heated with 50 ml. ogf 50% FeCl -solution and 50 ml. water in the manner described in Example 3. After recrystallization from ethanol-dioxane 7.4 g. (49%) of S-benzylamino-Z-(S-nitrofuryl)-l,3,4-thiadiazole in the form of yellowish brown crystals, M.P. 190.5-191.5 C., are obtained.
  • Example 16.5-(Z-Phenylethylamino)-2-(5-Nitr0furyl)- 1,3,4-Thiadiaz0le 2.5 g. of 1-(S-nitrofurfural)-4-(2-phenylethyl)-thiosemicarbazone are heated with ml. of 50% FeCl -solution and 10 ml. water in the manner described in Example 3. After recrystallization from ethanol 1.9 g. (76%) of 5 (Z-phenylethyl amino) -2- (5 -nitrofuryl) -1,3 ,4-thiadiazole are obtained in the form of brilliant yellow crystals, which due to polymorphi melt at 160169 C.
  • Example 1 7.5 -Pheny lamina-Z- (5 -N itrofuryl 1,3,4-Thiadiaz0le 8.1 g. of I-(S-nitrofur-fural)-4-phenylthiosemicarbazone are heated with 30 ml. of 50% FeCl -solution and 30 ml. water as described in Example 3. After recrystallization from ethanol-dioxane 5.1 g. (59%) of S-phenylamino- Z-(S-nitrofuryl) -1,3,4 -thiadiazo1e are obtained in the form of light yellow crystals which are decomposed at 253-254.5 C.
  • Example 1 8 (Z-Pyridylamino -2- (5 -N itrofuryl 1,3,4-Thiadiaz0le 2.9 g. of 1-(5-nitrofurfural)-4-(2-pyridyl)-thiosemicarbazone are heated with 10 ml. of 50% FeCl -solution and 10 ml. Water in the manner described in Example 3. After recrystallization from dimethylformamide 1.7 g. (59%) of S-(Z-pyridylamino)-2-(5-nitrofuryl)-l,3,4-thiadiazole are obtained in the form of brilliant filthy needles, which are decomposed at 330-340 C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

Description

United States Patent 3,025,303 Patented Mar. 13, 1962 htice This invention relates to a new group of compounds possessing valuable properties as chemo therapeutics. More particularly this invention relates to amino-nitrofuryl-thiadiazoles which may be represented by the following general formula:
wherein A is selected from the group consisting of NH and substituted NH -groups containing substituents having from 1 to 8 carbon atoms, for example alkyl radicals such as methyl, ethyl, n propyl, isopropyl, n-bu-ty l, isobutyl or allyl, a substituted alkyl such as carboxy methyl, aryl radicals such as phenyl, aralkyl radicals such as benzy-l or phenethyl, alicyclic groups such as cyclohexyl, heterocyclic groups such as pyridyl. Thus, for example, the amino group may consist of a secondary amino group" having such a substituent.
The novel compounds according to the invention have proved to possess surprisingly strong antibacterial activity and at the same time a remarkably low toxicity.
The invention also includes a process for producing the described compounds, which comprises treating S-nitrofurfuralthiosemicarbazones with oxidizing agents causing an oxidative ring closure of the semicarbazone with formation of the corresponding thiadiazole compounds.
The reaction taking place may be illustrated by the following reaction formula:
wherein A has the significance indicated above.
As example of a suitable oxidizing agents for this process may be mentioned salts of metals which occur in several oxidation stages, especially ferric salts, such as ferric chloride, ferric ammonium sulfate, potassium ferric sulfate, potassium ferric cyanide, sodium ferric cyanide, potassium ferric oxalate, sodium ferric oxalate, ferric ammonium citrate, ferric nitrate, ferric phosphate, ferric formate, ferric acetate and feric benzo ate.
The oxidizing reaction is preferably carried out by treating the compound to be oxidized in aqueous suspension with the oxidizing agent, suitably at elevated temperature, for example 60-90 C. The oxidation can also be carried out electrolytically.
As already stated above, the novel compounds accord ing to the invention possess very strong antibacterial activity and it has been found that said activity in certain cases is practically independent of the kind of the substituents attached to the nitrogen atom in the amino group A. This is shown more in detail in the tables below.
In the Table I are stated those concentrations of the compound S-aminQ-Z-(S-nitrofuryl) 1,3,4 thiadiazole with unsubstituted amino group, wherein consequently A=NH which cause total inhibition of growth of a number of different micro organisms. In the Table II are stated the lowest concentrations of compounds having diiierent amino groups, which cause total inhibition of the growth of Staph. aureus.
TABLE I Bacteriostatic Efiect of the Compound 5 -Amino-2-(5- N itrofuryl -1 ,3,4-Thiadiaz0le Wherein A=NH Micro organism Without With 20 serum serum Staph. aureus 1/160, 000 1/160, 000 E. coli 1/640, 000 1/640, 000 S. pamiyphi N 1/1, 280, 000 1/2, 560, 000 S. tllphimuri 1/1, 280, 000 1/1, 280. 000 S. cholera suis 1/640, 000 1/320, 000 S. typlii 1/1, 280, 000 1/2, 560, 000 Str. dysgalactz'ue 1/40. 000 1/20, 000 M. tuberculosis 1/40, 000 1/40, 000
TABLE II Bacteriostatic E fiect on Staph. Aureus 0f the Compound S-Amino-Z-(Nitrofuryl) -1,3,4-Thiadiazole With Difierent S ubstituents in the Amino Group.
Amino group: Without serum NH 1/160,000 NHCH3 1/s0,000 NHC3H7 1/s0,000 NHCH2CH=CH2 1/40,000 NHCSHU 1/s0,000 NHCH2C6H5 1/320,000 NHCH2CO2C2H5 1/s0,000
As examples of other micro organisms on which the compounds in question have proved to possess a strong growth inhibiting effect may be mentioned strains of the geni Salmonella and Shigella, bacetria of coliand streptococcus types, Haemophilus influenzae, Trichomonas vaginalis and Trichophyton.
It is well known that many compounds containing the nitrofuran nucleu possess antibacterial properties. The surprisingly strong antibacterial activity of the novel compounds according to the invention is due to the combination of the nitrofuryl group with the thiadiazole group in such a way that both these radicals are contained in the molecule which is a condition for the characteristic antibacterial spectrum obtained by the compounds of the invention. This will be apparent by a comparison between the following substances:
(1) 5 (2 nitrofuryl)-2 amino-thiadiazole-1,3,4-, cording to the invention.
i u i OzN-C 0-0 \O/ (2) 5-nitrofurfurylidenthiosemicarbazide.
(3 5-fu=ryl-2-aminothiadiazole-1,3 ,4.
H N N As will be seen from the table, the substance No. 1, i.e. the compound according to the invention, has a bacteriostatic effect of a very much higher order of magnitude than the substances Nos. 2 and 3.
Especially valuable among the nitrofurylthiadiazole compounds according to the invention are 5-amino-2-(5- nitrofuryl) 1,3,4-thiadiazole, 5-methylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole, 5-ethylamino 2 (5-nitrofuryl)- 1,3,4-thiadiazole, 5-allylamino 2 (5-nitrofuryl)-1,3,4- thiadiazole, 5 benzylamino 2 (5 nitrofuryl)-1,3,4- thiadiazole, and further also 5-cyclohexylamino-2-(5- nitrofuryl)-1,3,4-thiadiazole and 5-phenylamino-2-(5-nitrofuryl) l ,3 ,4-thiadiazole.
The process of the invention may be explained in greater detail by reference to the following specific examples which represent practical embodiments of our process.
Example I .-5 -Amino-2-( 5 -N itrofuryl ,3,4-Thiadiazole 164 g. of 5-nitro-2-furfuralthiosemicarbazone is suspended in 511 ml. water and 765 ml. of 50% ferric chloride solution is added thereto. The mixture is heated to 6090 C. for 45 minutes while stirring. The raw reaction product so obtained is recrystallized twice from diluted dimethylformamide. On cooling the solution, yellow crystals crystallize out which melt at 270-271 C. with decomposition, yield 94 g. (57%).
Example 2.--5 -A mino-Z- (5 -N itrofuryl ,3,4-Thiadiazle In an electrolysis vessel holding about 500 ml. is inserted a porous clay cell having a volume of about 200 ml. In this cell is poured a suspension of 21.4 g. of nitro-2-furfuralthiosemicarbazone in about 125 ml. potassium ferric sulfate solution. The suspension is stirred effectively by the aid of a rotating perforated platine anode with a surface of about 5 X4 cm.= cm. In the cathode space outside the clay cell diluted sulphuric acid is introduced and a cylinder-shaped cathode made from a sheet of copper, for example, is inserted therein.
After the cathode liquid has been heated to about 70 C. electrolysis is carried out with a current of about 2 amp. for 4 hours. The current is then opened and the content of the anodic cell is filtered. The raw reaction product is washed 5 times with hot water and then recrystallized from diluted dimethyl formamide. Melting point 270272 C. (decomposition). Yield 14 g. (65
Example 3.5-Met hylamin0 -2-(5-Nitro-2-Furyl) -1,3,4-
1 Tlziadiazole 16.4 g. of 1-(5-nitro-2-furfu-ral)-4-methylthiosemicarbazone is suspended in ml. water and 70 g. of 50% FeCl -solution is added thereto. The mixture is heated while stirring for 45 minutes. After cooling the crystals are filtered olf and washed with hot water. The raw reaction product so obtained is recrystallized from a mixture of ethanol and dioxane. Melting point 219221 C. (decomposition). Yield 10.4 g. (63%).
Example 4 .5 -A mino-Z- (5 -N itrofuryl -1 ,3 ,4-thiadiaz0le 6.5 g. of 5-nitro-2-furfuralthiosemicarbazone and 30 g. of ferric ammonium sulfate are mixed with 100 ml. water and heated on water bath for about 1 hour while stirring. The precipitate which is thus formed is filtered off and dried. Weight 5.1 g. After recrystallization from dintethyl sulfoxide 4.0 g. of 5-arnino-2-(5-nitrofuryl)- 1,3,4-thiadiazole is obtained which corresponds to a yield of 63%. M.P. 270-272 C. with decomposition.
Example 5 .-5-A min0-2-(5 -N itrofuryl ,3,4-Tl1iadiazole 4.2 g. of 5-nitro-2-furfuralthiosemicarbazone and 20 g. of potassium ferric cyanide in ml. water are heated on water bath for about 1 hour. The raw product so obtained is filtered off and dried and leaked with concentrated cold formic acid and filtered. The filtrate is diluted with water and hereby yellow crystals of 5-amino- 2-(5-nitrofuryl)-l,3,4-thiadiazole are formed which after drying weigh 2.4 g., corresponding to a yield of 57%. The compound is decomposed at 270-272 C.
Example 6 .5 -Ethylam ino-Z- 5 -N itrofuryl -1 ,3 ,4 T hiadiazole 24.2 g. of l-(5-nitrofurfural)-4-ethylthiosemicarbazone are treated with 100 ml. of 50% ferric chloride solution and 100 ml. water as described in Example 3. After recrystallization from ethanol-dioxane 13.7 g. (57%) of 5-ethylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole are obtained in the form of yellowish brown needles, M.P. 219- 221.5 C.
Example 7.-5-n-Pr0pylamino-2-(S-Nitrofuryl) -1,3,4- Tlziadiazole 25.6 g. of 1-(5-nitrofurfural)-4-n-propylthiosemicarbazone are treated with 100 ml. of 50% FeCl -solution and 100 ml. water in the manner described in Example 3. After recrystallization from ethanol 16.3 g. (64%) of 5-n-propylamino 2-(S-nitrofuryl)-l,3,4-thiadiazole are obtained in the form of yellow needles, M.P. -191 C.
Example 8.-5-Is0pr0pylamin0-2-(5-Nitr0furyl) 1,3,4-Tlziadiaz0le 18.8 g. of I-(S-nitrofurfural)-4-isopropylthiosemi-carbazone are treated with 70 ml. of 50% FeCl -solution and 70 ml. water as described in Example 3. After recrystallization from ethanol-dioxane 12 g. (65%) of 5-isopropylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole in the form of brilliant yellow scales, M.P. 213-215 C. are obtained.
Example 9.5 -N -Buty laminO-Z- 5 -N itrofuryl 1,3,4-Thiadiaz0le 27 g. of I-(S-nitrofurfural)-4-n-butylthiosemicarbazide are treated with 100 ml. of 50% FeCl -solution and 100 ml. water as described in Example 3. After recrystallization from ethanol-dioxane 15.7 g. (58%) of S-n-butylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole in the form of yellow needles are obtained. M.P. 186187 C.
Example 10.5-Is0butylamin0-2-(S-Nitrofuryl)- 1,3,4-Tl1iadiazole 13.5 g. of 1-(S-nitrofurfural)-4-isobutylthiosemicarbazone are treated with 50 ml. of Fecl -solution and 50 ml. water as described in Example 3. After recrystallization from ethanol 8.8 g. (65%) of S-isobutylamino-Z-(S-nitrofuryl)-1,3,4-thiadiazole are obtained in the form of yellow scales. M.P. 183.5-184.5 C.
Example 1 I .5 -N -H exy IaminO-Z- 5 -N itrofuryl 1 ,3,4- Th iadiazole 11.9 g. of 1-(S-nitrofurfural)-4-n-hexylthiosemicarbazone are heated with 40 ml. of 50% FeCl -solution and 40 ml. water in the manner described in Example 3. After recrystallization from ethanol 5.8 g. (49%) of S-n-hexylamino-2-(5-nitrofuryl)-l,3,4-thiadiazole in the form of yellow crystals are obtained. M.P. 162.5163.5 C.
Example 12.-5-A llylamino-Z-(S-Nitrofuryl) 1,3,4-Thiadiazole 25.4 g. of 1-(5-nitrofurfural)-4-allylthiosemicarbazone are reacted with ferric chloride and water as described in Example 3. After recrystallization from ethanol 18.3 g. (72%) of 5-allylamino-2-(S-nitrofuryl)-1,3,4-thiadiazole are obtained in the form of a mixture of brownish yellow needles and yellow scales, which latter on heating are converted to the former kind of crystals which melt at 172.5-175.5 C.
Example 13.5-Carboxymethylamino-Z-(S-Nitrofuryl) 1,3,4-Thiadiazle 2.5 g. of I-(S-nitrofurfural)-4-carbethoxymethylthiosemicarbazone are treated with 10 ml. of 50% FeCl solution and 10 ml. water in the manner described in Example 3. After recrystallization from ethanol 2.0 g. of -carbethoxymethylamino-2-nitrofuryl-1,3,4-thiadiazole in the form of yellow scales, M.P. l72.5-174 C. are obtained.
0.9 g. of the carboxymethyl derivative is heated for 3 hours with 20 ml. of 5 normal sulfuric acid. The resulting substance is filtered off, washed and dried. After recrystallization from dioxane-ethanol 0.8 g. of S-carboxymet-hylamino-Z-(S nitrofuryl) 1,3,4 thiadiazole in the form of light yellow crystals are obtained. M.P. 246- 248 C.
Example 14.5- (Z-Methoxyethylamino) -2-(5-Nitr0- furyl) ,3,4-Thiadiaz0le 4.1 g. of 1-(S-nitrofurfural)-4-(2-methoxyethyl)-thiosemicarbazone are heated with 15 ml. of 50% FeCl solution and 50 ml. water as described in Example 3. After recrystallization from ethanol 3.0 g. (74%) of 5-(2-methoxyethylamino)-2-(5 nitrofuryl) 1,3,4 thiadiazole in the form of yellow needles ar obtained. M.P. 169-171 C.
Example 15.-5-Benzylamin0-2-(5-Nitrofuryl)- 1,3,4-Thiadiaz0le 15.2 g. of 1-(5-nitrofurfural)-4-benzylthiosemicarbazone are heated with 50 ml. ogf 50% FeCl -solution and 50 ml. water in the manner described in Example 3. After recrystallization from ethanol-dioxane 7.4 g. (49%) of S-benzylamino-Z-(S-nitrofuryl)-l,3,4-thiadiazole in the form of yellowish brown crystals, M.P. 190.5-191.5 C., are obtained.
Example 16.5-(Z-Phenylethylamino)-2-(5-Nitr0furyl)- 1,3,4-Thiadiaz0le 2.5 g. of 1-(S-nitrofurfural)-4-(2-phenylethyl)-thiosemicarbazone are heated with ml. of 50% FeCl -solution and 10 ml. water in the manner described in Example 3. After recrystallization from ethanol 1.9 g. (76%) of 5 (Z-phenylethyl amino) -2- (5 -nitrofuryl) -1,3 ,4-thiadiazole are obtained in the form of brilliant yellow crystals, which due to polymorphi melt at 160169 C.
Example 1 7.5 -Pheny lamina-Z- (5 -N itrofuryl 1,3,4-Thiadiaz0le 8.1 g. of I-(S-nitrofur-fural)-4-phenylthiosemicarbazone are heated with 30 ml. of 50% FeCl -solution and 30 ml. water as described in Example 3. After recrystallization from ethanol-dioxane 5.1 g. (59%) of S-phenylamino- Z-(S-nitrofuryl) -1,3,4 -thiadiazo1e are obtained in the form of light yellow crystals which are decomposed at 253-254.5 C.
Example 1 8 .5 (Z-Pyridylamino -2- (5 -N itrofuryl 1,3,4-Thiadiaz0le 2.9 g. of 1-(5-nitrofurfural)-4-(2-pyridyl)-thiosemicarbazone are heated with 10 ml. of 50% FeCl -solution and 10 ml. Water in the manner described in Example 3. After recrystallization from dimethylformamide 1.7 g. (59%) of S-(Z-pyridylamino)-2-(5-nitrofuryl)-l,3,4-thiadiazole are obtained in the form of brilliant filthy needles, which are decomposed at 330-340 C.
Example 19.5-Cycl0hexylamin0-2-(5-Nilr0furyl)- 1,3,4-Tlziadiazole 29.6 g. of 1-(S-nitrofurfural)-4-cyclohexylthiosemicarbazide are carefully pulverized and heated with FeCl solution and water as described in Example 3. The raw product so obtained consisting of brown balls are washed, dried and recrystallized from ethanol. Hereby a mixture of brown scales and yellow filthy crystals is obtained, both kinds of which are decomposed at l-178 C. Yield 21.8 g. (73%).
What we claim is:
1. A compound of the formula:
References Cited in the file of this patent Collonna et al.: Chem. Abstracts, vol. 44, column 128 (1950).
Bambas: Chem. of Heterocyclic Compds, vol. 4, pages 106,1l2-113 (1952).

Claims (1)

1. A COMPOUND OF THE FORMULA:
US763464A 1957-09-30 1958-09-26 Certain nitrofuryl, thiadiazolyl amines Expired - Lifetime US3025303A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SE852795X 1957-09-30

Publications (1)

Publication Number Publication Date
US3025303A true US3025303A (en) 1962-03-13

Family

ID=20362708

Family Applications (1)

Application Number Title Priority Date Filing Date
US763464A Expired - Lifetime US3025303A (en) 1957-09-30 1958-09-26 Certain nitrofuryl, thiadiazolyl amines

Country Status (4)

Country Link
US (1) US3025303A (en)
DE (1) DE1077220B (en)
FR (1) FR1291518A (en)
GB (1) GB852795A (en)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3124588A (en) * 1964-03-10 Z-acylamtoo-s-nitrothiazole
US3134784A (en) * 1962-06-15 1964-05-26 American Cyanamid Co N,n'-diethylene-n"-(1,3,4-thiadiazol-2-yl) phosphoramides
US3452035A (en) * 1966-12-23 1969-06-24 American Cyanamid Co 2 - amino - 5 - (5 - nitro - 1 - substituted-2 - imidazolyl) - 1,3,4 - thiadiazoles and oxadiazoles
US3452034A (en) * 1967-03-09 1969-06-24 American Cyanamid Co Substituted 2-(1,3,4-thiadiazol-2-yl)-4(5)-nitroimidazoles
US3666860A (en) * 1966-12-23 1972-05-30 Gerald Berkelhammer Substituted nitroimidazolylthiadiazoles and oxadiazoles as antiprotozoal agents
US3904756A (en) * 1966-12-23 1975-09-09 American Cyanamid Co Substituted nitroimidazolyl thiadiazoles and oxadiazoles as antibacterial agents and growth promoting compounds
US3931209A (en) * 1974-03-28 1976-01-06 Velsicol Chemical Corporation 2-Alkyl-4-thiadiazolyl-1,2,4-triazolidin-3-ones
US3933839A (en) * 1974-03-11 1976-01-20 Velsicol Chemical Corporation Thiadiazolylimidazolines
US3991200A (en) * 1974-04-25 1976-11-09 American Cyanamid Company Substituted nitroimidazolyl thiadiazoles and oxadiazoles as antibacterial agents and growth promoting compounds
US4065567A (en) * 1966-12-23 1977-12-27 American Cyanamid Company Substituted nitroimidazolyl thiadiazoles and oxadiazoles as antibacterial agents and growth promoting compounds
US4404070A (en) * 1982-07-23 1983-09-13 Celanese Corporation Electrochemical production of 2,6-diaminobenzobisthiazole

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1138783B (en) * 1959-07-13 1962-10-31 Pharmacia Ab Process for the production of new bacteriostatically active nitrofurylthiadiazoles
DE1134996B (en) * 1959-07-13 1962-08-23 Pharmacia Ab Process for the production of new, bacteriostatically active nitrofurylthiadiazoles
US3055910A (en) * 1961-01-11 1962-09-25 Abbott Lab Hydrazinonitrofurylthiazoles
NL121520C (en) * 1961-03-07

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3124588A (en) * 1964-03-10 Z-acylamtoo-s-nitrothiazole
US3134784A (en) * 1962-06-15 1964-05-26 American Cyanamid Co N,n'-diethylene-n"-(1,3,4-thiadiazol-2-yl) phosphoramides
US3452035A (en) * 1966-12-23 1969-06-24 American Cyanamid Co 2 - amino - 5 - (5 - nitro - 1 - substituted-2 - imidazolyl) - 1,3,4 - thiadiazoles and oxadiazoles
US3666860A (en) * 1966-12-23 1972-05-30 Gerald Berkelhammer Substituted nitroimidazolylthiadiazoles and oxadiazoles as antiprotozoal agents
US3904756A (en) * 1966-12-23 1975-09-09 American Cyanamid Co Substituted nitroimidazolyl thiadiazoles and oxadiazoles as antibacterial agents and growth promoting compounds
US4065567A (en) * 1966-12-23 1977-12-27 American Cyanamid Company Substituted nitroimidazolyl thiadiazoles and oxadiazoles as antibacterial agents and growth promoting compounds
US3452034A (en) * 1967-03-09 1969-06-24 American Cyanamid Co Substituted 2-(1,3,4-thiadiazol-2-yl)-4(5)-nitroimidazoles
US3933839A (en) * 1974-03-11 1976-01-20 Velsicol Chemical Corporation Thiadiazolylimidazolines
US3931209A (en) * 1974-03-28 1976-01-06 Velsicol Chemical Corporation 2-Alkyl-4-thiadiazolyl-1,2,4-triazolidin-3-ones
US3991200A (en) * 1974-04-25 1976-11-09 American Cyanamid Company Substituted nitroimidazolyl thiadiazoles and oxadiazoles as antibacterial agents and growth promoting compounds
US4404070A (en) * 1982-07-23 1983-09-13 Celanese Corporation Electrochemical production of 2,6-diaminobenzobisthiazole

Also Published As

Publication number Publication date
DE1077220B (en) 1960-03-10
GB852795A (en) 1960-11-02
FR1291518A (en) 1962-04-27

Similar Documents

Publication Publication Date Title
US3025303A (en) Certain nitrofuryl, thiadiazolyl amines
Dogan et al. Synthesis, structure elucidation and antimicrobial activity of some 3-hydroxy-2-naphthoic acid hydrazide derivatives
US3755350A (en) Substituted 3-phenyl hydantoins useful as fungicides
US3843668A (en) Certain 4-substituted amino-2,1,3-benzothiadiozoles
Golovlyova et al. Synthesis of novel five-membered nitrogen-containing heterocyclic compounds from derivatives of arylsulfonyl-and arylthioacetic and-propionic acids
CA2650385A1 (en) Novel imidazole derivatives, preparation and user thereof as medicine
US4374843A (en) 2-Guanidino-4-heteroarylthiazoles
Farhan et al. Heterocyclization of isoniazid: synthesis and antimicrobial activity of some new pyrimidine, 1, 3-thiazole, 1, 2, 4-thiadiazole, and 1, 2, 4-triazole derivatives derived from isoniazid
Hassan et al. New access to pyrazole, oxa (thia) diazole and oxadiazine derivatives
Baines et al. 5-(Arylamino)-1, 2, 3-triazoles and 5-amino-1-aryl-1, 2, 3-triazoles from 3-(cyanomethyl) triazenes
US2759932A (en) Series of new n-(5-nitro-2-furfurylidene)-3-amino-2-iminooxazolidines
US3557099A (en) Nitrofuryl-oxadiazole derivatives
CH408945A (en) Process for the preparation of heterocyclic compounds
DE69225906T2 (en) HETEROCYCLIC COMPOUND AND THIS CARDIOTONIC CONTAINING IT AS AN ACTIVE COMPONENT
NO130671B (en)
US2945047A (en) Thiosemicarbazides
US2980677A (en) Certificate of correction
US3231570A (en) Nitrofurans
US2714110A (en) Substituted triazoles and method of preparing same
DE2204767A1 (en) Substd thia-and oxadiazoles - useful as optical brighteners
US4590299A (en) 2-guanidino-4-heteroarylthiazoles
US3644344A (en) Nitrofurylacrylidene derivatives
US3317551A (en) 2-substituted-5-(5-nitro-2-furyl)-1, 3, 4-thiadiazoles
US3660419A (en) Disubstituted-5-nitroimidazoles
US3514451A (en) Novel 2-substituted 5-nitrofurans and a process for the preparation thereof