CS252337B1 - Method of new 2-(4-tert.aminophenylthiomethyl)benzoic acids preparation - Google Patents
Method of new 2-(4-tert.aminophenylthiomethyl)benzoic acids preparation Download PDFInfo
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- CS252337B1 CS252337B1 CS863310A CS331086A CS252337B1 CS 252337 B1 CS252337 B1 CS 252337B1 CS 863310 A CS863310 A CS 863310A CS 331086 A CS331086 A CS 331086A CS 252337 B1 CS252337 B1 CS 252337B1
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- Prior art keywords
- tert
- formula
- aminophenylthiomethyl
- benzoic acids
- new
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 235000010233 benzoic acid Nutrition 0.000 title claims abstract description 5
- 150000001559 benzoic acids Chemical class 0.000 title claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 claims abstract description 14
- -1 dimethylamino, pyrrolidino, piperidino Chemical group 0.000 claims abstract description 5
- 238000009835 boiling Methods 0.000 claims abstract description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract description 3
- 159000000000 sodium salts Chemical class 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- CPEONABTMRSIKA-UHFFFAOYSA-N 1,4$l^{2}-oxazinane Chemical group C1COCC[N]1 CPEONABTMRSIKA-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract description 2
- 230000000508 neurotrophic effect Effects 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 abstract 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- PQSBRHXGVPVYFJ-UHFFFAOYSA-N 4-(dimethylamino)benzenethiol Chemical compound CN(C)C1=CC=C(S)C=C1 PQSBRHXGVPVYFJ-UHFFFAOYSA-N 0.000 description 2
- CIYSQIBVUOZMOU-UHFFFAOYSA-N 4-morpholin-4-ylbenzenethiol Chemical compound C1=CC(S)=CC=C1N1CCOCC1 CIYSQIBVUOZMOU-UHFFFAOYSA-N 0.000 description 2
- UYAAIPBKIPVXNA-UHFFFAOYSA-N 4-pyrrolidin-1-ylbenzenethiol Chemical compound C1=CC(S)=CC=C1N1CCCC1 UYAAIPBKIPVXNA-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229940071264 lithium citrate Drugs 0.000 description 2
- WJSIUCDMWSDDCE-UHFFFAOYSA-K lithium citrate (anhydrous) Chemical compound [Li+].[Li+].[Li+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WJSIUCDMWSDDCE-UHFFFAOYSA-K 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CZRNFWCUUAGUCQ-UHFFFAOYSA-N 2-[(4-piperidin-1-ylphenyl)sulfanylmethyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CSC1=CC=C(N2CCCCC2)C=C1 CZRNFWCUUAGUCQ-UHFFFAOYSA-N 0.000 description 1
- XAJPURQMMOKCTK-UHFFFAOYSA-N 4-piperidin-1-ylbenzenethiol Chemical compound C1=CC(S)=CC=C1N1CCCCC1 XAJPURQMMOKCTK-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Řešení se týká oboru synthesy léčiv. Jeho předmětem je způsob přípravy nových 2-/4-tero.aminofenylthiometyl/benzoových kyselin obecného vzorce I, /-CH2S-Á R COOH ve kterém R značí zbytek dimetylamino, pyrrolidino, piperidino nebo morfolino. Látky vzorce I jsou meziprokukty synthesy neurotropně účinných léčiv. Způsob přípravy spočívá v reakcích ftalidu se sodnými solemi příslušných 4-/terc.amino/thiofenolů ve vroucím etanolu.The present invention relates to the field of drug synthesis. Its subject is a way of preparing new ones 2- (4-tert-aminophenylthiomethyl) benzoic acids of formula I, / -CH 2 S -R R COOH wherein R is dimethylamino, pyrrolidino, piperidino or morpholino. The compounds of formula I are intermediates of the synthesis neurotrophic drugs. Method of preparation consists in the reaction of phthalide with sodium salts of the corresponding 4- (tert-amino / thiophenols) boiling ethanol.
Description
Tento vynález se týká způsobu přípravy nových 2-/4/terc.aminofenylthiometyl/benzoových kyselin obecného vzorce I, /1/The present invention relates to a process for the preparation of novel 2- (4) tertiaminophenylthiomethyl (benzoic acids) of the formula
COOH ve kterém R značí zbytek dimetylamino, pyrrolidino, piperidino nebo morfolinoCOOH wherein R represents a dimethylamino, pyrrolidino, piperidino or morpholino radical
Látky podle vynálezu vzorce I jsou meziprodukty synthesy neurotropních léčiv. Způsob přípravy látek vzorce I podle tohoto vynálezu spočívá v reakci ftalidu se sodnými solemi 4-/terc.amino/thiofenolů obecného vzorce II,The compounds of the invention of formula I are intermediates in the synthesis of neurotrophic drugs. The process for the preparation of the compounds of the formula I according to the invention consists in reacting the phthalide with the sodium salts of the 4- (tert.amino) thiophenols of the formula II,
HSHS
/11/ ve kterém R značí totéž jako ve vzorci I, ve vroucím etanolu.(11) wherein R is the same as in Formula I, in boiling ethanol.
Výchozí 4-/terc.amino/thiofenoly byly vesměs v literatuře popsány: 4-/dimetylamino/thiofenol /viz Banfield J.E., J.Chem.Soc. 1960, 456/ a ostatní, tj. 4-pyrrolidinothiofenol, 4-piperidinothiofenol a 4-morfolinothiofenol v prácí Kmoníček V. et al., Collect. Czech. Chem. Commun. 51, 937 /1986/, Podrobnosti tohoto způsobu přípravy jsou uvedeny v příkladech, jejichž účelem je ilustrovat možnosti vynálezu, avšak ne všechny tyto možnosti vyčerpávajícím způsobem popsat. Látky vzorce I podle tohoto vynálezu jsou nové. Jejioh identita byla zajištěna jednak analysami, jednak obvyklými spektrálními metodami. Jsou to látky vesměs krystalické, ve vodě velmi málo rozpustné, rozpouštějící se však v roztocích alkalických hydroxidů a uhličitanů na roztoky příslušných alkalických solí.The starting 4- (tert.amino) thiophenols have been described in the literature in general: 4- (dimethylamino) thiophenol] see Banfield J.E., J.Chem.Soc. 1960, 456) and others, i.e., 4-pyrrolidinothiophenol, 4-piperidinothiophenol and 4-morpholinothiophenol in the work of Kmoníček V. et al., Collect. Czech. Chem. Commun. 51, 937 (1986). Details of this method of preparation are given in the examples, which are intended to illustrate the possibilities of the invention, but not all of these possibilities are exhaustively described. The compounds of formula I according to the invention are novel. Its identity was ensured both by analyzes and by usual spectral methods. They are mostly crystalline substances, which are very poorly soluble in water, but dissolve in solutions of alkali hydroxides and carbonates into solutions of the corresponding alkali salts.
Příklad 1Example 1
2-{^-/Dimetylamino/fenylthiometyl] benzoová kyselina /1, R = dimetylamino/2 - {[1- (Dimethylamino) phenylthiomethyl] benzoic acid (1, R = dimethylamino)
Rozpuštěním 4,1 g sodíku ve 200 ml etanolu se připraví roztok ethoxidu sodného, přidá se 27,4-g 4-/dimetylamino/thiofenolu /lit.cirována/ a 23,0 g ftalidu, a směs se vaří 3 h pod zpětným chladičem. Etanol se odpař! ve vakuu, zbytek se rozpustí ve 100 ml vody, roztok se u zfiltruje a filtrát se neutralisuje kyselinou octovou na p 6. Stáním přes noc a filtrací se získá 33,2 g /65 %/ surového produktu, t.t. 140 až 145 °C. Analytický vzorek se připraví rekrystalisacl z vodného etanolu, t.t. 151 až 153 °C.Dissolve 4.1 g of sodium in 200 ml of ethanol to prepare a sodium ethoxide solution, add 27.4 g of 4- (dimethylamino) thiophenol / lithium citrate and 23.0 g of phthalide, and reflux for 3 h. . Ethanol is evaporated! in vacuo, the residue was dissolved in 100 ml of water, the solution was filtered, and the filtrate was neutralized with acetic acid to pH 6. Standing overnight and filtration gave 33.2 g (65%) of the crude product, m.p. Mp 140-145 ° C. An analytical sample was prepared by recrystallization from aqueous ethanol, m.p. Mp 151-153 ° C.
Příklad 2Example 2
2-/4-Pyrrolidinofenylthiometyl/benzoová kyselina /1, Ř - pyrrolidino/2- (4-Pyrrolidinophenylthiomethyl) benzoic acid (1, R-pyrrolidino)
Připraví se podobně jako v příkladu 1 z 12,0 g 4-pyrrolidinothiofenolu /lit.citována/, 8,7 g ftalidu a ethoxidu sodného /ž 1,62 g sodíku/ ve 100 ml etanolu; 10,2 g /50 % /, t.t. 193 až 195 °C /etanol/.Prepared in analogy to Example 1 from 12.0 g of 4-pyrrolidinothiophenol (lithium citrate), 8.7 g of phthalide and sodium ethoxide (1,6 1.62 g of sodium) in 100 ml of ethanol; 10.2 g (50%), m.p. 193 DEG-195 DEG C. (ethanol).
P i.í k 1 a d 3Example 1 and d 3
2-/4-Piperidinofenylthiometyl/benzoová kyselina /1, R - piperidino/2- (4-Piperidinophenylthiomethyl) benzoic acid (1, R-piperidino)
Připraví se podobně jako předešlé dva produkty z 19,2 g 4-piperidinothlofenolu /lit.citována/, 13,0 g ftalidu a ethoxidu sodného /z 2,3 g sodíku/ v 80 ml etanolu; 14,5 g /45 %/, t.t. 146 až 148 °C /vodný etanol/.Prepared in analogy to the previous two products from 19.2 g of 4-piperidinothlophenol (lithium cited), 13.0 g of phthalide and sodium ethoxide (from 2.3 g of sodium) in 80 ml of ethanol; 14.5 g (45%), m.p. 146-148 ° C (aqueous ethanol).
Příklad 4Example 4
2-/4-Morfolinofenylthiometyl/ benzoová kyselina /1, R = morfolino/2- (4-Morpholinophenylthiomethyl) benzoic acid (1, R = morpholino)
Připraví se podobně jako předešlé z 11,7 g 4-morfolinothiofenolu /lit.citována/, 7,5 g ftalidu a ethoxidu sodného /z 1,38 g sodíku/ v 50 ml etanolu; 11,6 g /60 %/, t.t. 123 až 124 °C /vodný metanol/.Prepared in analogy to the previous procedure from 11.7 g of 4-morpholinothiophenol (lithium cited), 7.5 g of phthalide and sodium ethoxide (from 1.38 g of sodium) in 50 ml of ethanol; 11.6 g (60%), m.p. 123 DEG-124 DEG C. (aqueous methanol).
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS863310A CS252337B1 (en) | 1986-05-07 | 1986-05-07 | Method of new 2-(4-tert.aminophenylthiomethyl)benzoic acids preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS863310A CS252337B1 (en) | 1986-05-07 | 1986-05-07 | Method of new 2-(4-tert.aminophenylthiomethyl)benzoic acids preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS331086A1 CS331086A1 (en) | 1987-01-15 |
| CS252337B1 true CS252337B1 (en) | 1987-08-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS863310A CS252337B1 (en) | 1986-05-07 | 1986-05-07 | Method of new 2-(4-tert.aminophenylthiomethyl)benzoic acids preparation |
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| Country | Link |
|---|---|
| CS (1) | CS252337B1 (en) |
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1986
- 1986-05-07 CS CS863310A patent/CS252337B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS331086A1 (en) | 1987-01-15 |
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