CS272570B1 - Method of 2-chlorophenylamidohydrazone preparation - Google Patents
Method of 2-chlorophenylamidohydrazone preparation Download PDFInfo
- Publication number
- CS272570B1 CS272570B1 CS347288A CS347288A CS272570B1 CS 272570 B1 CS272570 B1 CS 272570B1 CS 347288 A CS347288 A CS 347288A CS 347288 A CS347288 A CS 347288A CS 272570 B1 CS272570 B1 CS 272570B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- toluene
- preparation
- chlorophenylamidohydrazone
- hydrazine
- chlorothiobenzamide
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims abstract description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 51
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- FLQYOORLPNYQEV-UHFFFAOYSA-N 2-chlorobenzenecarbothioamide Chemical compound NC(=S)C1=CC=CC=C1Cl FLQYOORLPNYQEV-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000012485 toluene extract Substances 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 1
- -1 2-chlorophenyl amide hydrazone Chemical class 0.000 abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002351 wastewater Substances 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 2
- 238000005273 aeration Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- HFBHPHBIBAUDNE-UHFFFAOYSA-N 2h-1,2,4-triazin-3-one Chemical class O=C1N=CC=NN1 HFBHPHBIBAUDNE-UHFFFAOYSA-N 0.000 description 1
- MUIKNZDODWUQCF-UHFFFAOYSA-N ClC1=C(C=CC=C1)N(N)C(N)=N Chemical compound ClC1=C(C=CC=C1)N(N)C(N)=N MUIKNZDODWUQCF-UHFFFAOYSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000010796 biological waste Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005980 thioamidation reaction Methods 0.000 description 1
- 238000004065 wastewater treatment Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Vynález se týká způsobu přípravy 2-chlorfenylamidohydrazonu z 2-chlorbenzonitrilu, který se konvertuje na 2-chlorthiobenzamid a po extrakci toluenem bez izolace krystalického thioamidu se toluenový extrakt zpracuje reakcí s hydrazínem na žádaný 2-chlorfenylamidohydrazon.The invention relates to a process for the preparation of 2-chlorophenylamidohydrazone from 2-chlorobenzonitrile, which is converted to 2-chlorothiobenzamide and, after toluene extraction without isolation of crystalline thioamide, the toluene extract is treated with hydrazine to give the desired 2-chlorophenylamidohydrazone.
Použití 2-chlorfenylamidohydrazonu nebo-li 2-chlorfenylhydrazinkarboximidamidu bude patrně analogické jako u 4-chlorfenyíamidohydrazonu, tj. k synthese protinádorových prostředků ve formě komplexů s platinou, k přípravě 1,2,4-triazinonů apod. Příprava 2-chlorfenylamidohydrazonu není v dostupné literatuře, např. Beilsteins Handbuch ěi Chemical Abstracts do roku 1987 uvedena a nebo v jiných souvislostech citována. Příčinou je nemožnost jeho přípravy klasickou Pionérovou cestou z aromatického nitrilu přes imidát na amidhydrazon podle následující reakční sekvence:The use of 2-chlorophenylamidohydrazone or 2-chlorophenylhydrazinecarboximidamide is likely to be analogous to that of 4-chlorophenyl amidohydrazone, ie the synthesis of antitumor agents in the form of platinum complexes, the preparation of 1,2,4-triazinones and the like. , e.g., Beilsteins Handbuch and Chemical Abstracts until 1987, or cited in other contexts. This is due to the impossibility of its preparation by the classical Pioneer route from aromatic nitrile via imidate to amidhydrazone according to the following reaction sequence:
ORSTEED
+ ROH + HCl+ ROH + HCl
-*-*·- * - * ·
HH.HC1 . OHHH.HC1. OH
------------>------------>
2.N2H^ /rozpouštědlo nh2 2.N 2 H 2 / solvent nh 2
C = N-NH2 ClC = N-NH 2 Cl
Postup přípravy 2-chlorfenylamidohydrazonu vyžadoval jako vstupní surovinu 2-chlorthiobenzamid v krystalické formě, tzn. jeho výrobku z 2-chlorbenzonitrilu včetně separace thioamidu v krystalické formě.The process for the preparation of 2-chlorophenylamidohydrazone required 2-chlorothiobenzamide in the crystalline form as the feedstock. its product from 2-chlorobenzonitrile including separation of thioamide in crystalline form.
Nyní bylo nalezeno, že 2-chlorfenylamidohydrazon vzorceIt has now been found that the 2-chlorophenylamidohydrazone of formula
ClCl
C = N - 1¾ .C = N - 1¾.
hh2 se připraví z 2-chlorbenzonitrilu velmi výhodně podle tohoto vynálezu. Způsob přípravy 2-chlorfenylamidohydrazonu spočívá podle vynálezu v tom, že se 2-chlorbenzonitiil rozpustí v etanolu, přidá se katalyzátor triethylamin a pak se provede thioamidace vodným roztokem (NH^^S při teplotě 20 až 40 °C.hh 2 is prepared from 2-chlorobenzonitrile very preferably according to the invention. The process for the preparation of 2-chlorophenylamidohydrazone consists in dissolving 2-chlorobenzonithiil in ethanol, adding the triethylamine catalyst, and then conducting the thioamidation with an aqueous solution (NH 4 S) at 20 to 40 ° C.
Vzniklá reakční směs se zahustí za mírného vakua na minimální objem a k takto získanému oranžovému oleji se předloží ve stejném objemovém poměru voda a toluen a 2-chlorthiobenzamid se vytřepe do toluenové fáze. Toluenová fáze s obsahem thioamidu se promyje vodou a vodná fáze se extrahuje toluenem. Oba toluenové extrakty se spojí, předloží se k nim hydrazin a směs se ponechá stát asi 20 minut při normální teplotě. Potom se vyhřeje takto připravená směs na 80 °C a na této teplotě se drží asi 3C minut, načež se z horké reakční směsi oddestiluje za vakua toluen, voda a hydrazin, potom se k destilačnímu zbytku přidá studená voda, vzniklá směs se rozmíchá, ochladí a odfiltruje se surový produkt, který se na závěr promyje malým, množstvím vody, načež se suší ve vakuové sušárně při 50 až 60 °C.The resulting reaction mixture was concentrated under a slight vacuum to a minimum volume and the orange oil thus obtained was charged in equal volume with water / toluene and the 2-chlorothiobenzamide was shaken into the toluene phase. The thioamide-containing toluene phase is washed with water and the aqueous phase is extracted with toluene. The two toluene extracts were combined, hydrazine was added, and the mixture was allowed to stand for about 20 minutes at normal temperature. The mixture is heated to 80 DEG C. and held at this temperature for about 3 minutes, then toluene, water and hydrazine are distilled off from the hot reaction mixture, then cold water is added to the distillation residue, the mixture is stirred, cooled. and the crude product is filtered off, which is finally washed with a small amount of water and then dried in a vacuum oven at 50 to 60 ° C.
Uvedený postup přípravy 2-chlorfenylamidohydrazonu bez meziizolace stádia 0-chlorbenzenthioamidu je zcela originální a z dostupné literatury není znám jakýkoliv srovnatelný postup pro přípravu této sloučeniny. 7 porovnání s klasickou Pinnerovou cestou pro meta a para-substituované aromatické nitrily, popř. i některé orCS 272 570 Bl thosubstituované aromatické nitrily bez stérické zábrany, se jeví nový postup výtěžkově výhodnější, jednodušší a méně pracný.The above process for the preparation of 2-chlorophenylamidohydrazone without intermediate isolation of the O-chlorobenzenethioamide stage is quite original and no comparable process for the preparation of this compound is known from the available literature. 7 compared to the classical Pinner pathway for meta and para-substituted aromatic nitriles, respectively. Even some orCS 272 570 B1 thiosubstituted aromatic nitriles without steric hindrance, the new process appears to be more profitable, simpler and less laborious.
Přípravu 2-chlorfenylamidohydrazonu lze provádět ve smaltovaných nebo ocelových (tř. 17) násadových reaktorech s duplikátorem a s možností vakuové destilace. Odpadní vody z uzlu přípravy 2-chlorbenzenthioamidu lze po přídavku NaOH a aeraci vzduchem při teplotě 80 až 90 °C, (čímž se převedou S?'~ ionty S^O-j?“ ag SO^“) vypouštět do kanalizace. Odpadní vodu z finální přípravy amidohydrazonu se doporučuje extrahovat toluenem, čímž se separuje další podíl rozpuštěného amidohydrazonu a teprve takto zpracovanou odpadní vodu vypouštět na biologické čištění odpadních vod.The preparation of 2-chlorophenylamidohydrazone can be carried out in enamelled or steel (class 17) batch reactors with a duplicator and with the possibility of vacuum distillation. The waste water from the 2-chlorobenzenethioamide preparation node can be discharged into the sewer after the addition of NaOH and aeration at 80-90 ° C (thereby converting the SiO 2 ions and SO 2 “)). It is recommended to extract the waste water from the final preparation of amidohydrazone with toluene, thereby separating a further fraction of the dissolved amidohydrazone and only discharging the waste water thus treated for biological waste water treatment.
Následující příklad znázorňuje provedení podle vynálezu.The following example illustrates an embodiment of the invention.
PříkladExample
Do reaktoru se předloží 20 g 2-chlorbenzonitrilu a rozpustí se za míchání ve 100 ml ethanolu a 10 ml triethylaminu, potom se přidá 100 ml vodného roztoku (NH^i^S (s obsahem 453 g/1) a 2 h se míchá při normální teplotě. Průběh reakce se sleduje pomoci tenkovrstvé chromatografie. Jakmile je konverze nitrilu na thioamid úplná, oddestiluje se za normálního tlaku nebo za mírného vakua (80 až 90 kPa) prakticky veškerý ethanol a voda. Potom se přidá k resultujícímu oranžovému oleji 100 ml studené vody a 100 ml toluenu a 2-chlorbenzenthioamid se vytřepe do toluenu. Vodná vrstva se stočí a S ionty se likvidují po přídavku louhu sodného aerací vzduchem při 80 až 90 °C.The reactor was charged with 20 g of 2-chlorobenzonitrile and dissolved with stirring in 100 ml of ethanol and 10 ml of triethylamine, then 100 ml of an aqueous solution (NH4i2S (containing 453 g / l)) was added and stirred for 2 h. Once the conversion of the nitrile to the thioamide is complete, virtually all ethanol and water are distilled off under normal pressure or under a slight vacuum (80 to 90 kPa), then 100 ml of cold are added to the resulting orange oil. water and 100 ml of toluene and 2-chlorobenzenethioamide are shaken into toluene, the aqueous layer is centrifuged and the S ions are discarded after addition of sodium hydroxide by aeration at 80-90 ° C.
Toluenová vrstva ε obsahem 2-chlorbenzenthioamidu se promyje ještě 50 ml studené vody a vodná fáze se extrahuje ještě 50 ml toluenu. Oba toluenové extrakty se spojí, předloží se k nim 80 ml 80% hydrazin hydrátu a směs se ponechá 20 minut stát při normální teplotě. Potom se směs vyhřeje na 80 °C a 30 minut se při této teplotě míchá. Průběh reakce se sleduje tenkovrstvou chromatografií.The toluene layer ε containing 2-chlorobenzenethioamide is washed with a further 50 ml of cold water and the aqueous phase is extracted with a further 50 ml of toluene. The two toluene extracts were combined, treated with 80 ml of 80% hydrazine hydrate and allowed to stand at room temperature for 20 minutes. The mixture was then heated to 80 ° C and stirred at this temperature for 30 minutes. The progress of the reaction was monitored by thin layer chromatography.
Reakčni směs se zpracuje vakuovou destilací, čímž se oddestiluje většina toluenu, vody a hydrazinu. K destilačnímu zbytku se předloží 50 ml studené vody a po rozmíchání a eventuálním dochlazení směsi se odfiltruje suspenze surového 2-chlorfenylamidohydrazonu, která se opatrně promyje malým množstvím studené vody a produkt se suší ve vakuové sušárně při 50 až 60 °C.The reaction mixture was worked up by vacuum distillation to distill most of toluene, water and hydrazine. 50 ml of cold water is added to the distillation residue, and after stirring and possibly cooling the mixture, the suspension of crude 2-chlorophenylamidohydrazone is filtered off, which is carefully washed with a small amount of cold water and dried in a vacuum oven at 50 to 60 ° C.
Takto bylo získáno 16,5 g produktu (tj. 67 % na výchozí 2-chlorbenzonitril) s b. t. = 113 až 114,5 °C. Další podíl produktu lze získat extrakcí vodného filtrátu toluenem. Identita látky byla potvrzena hmotovou spektroskopií.16.5 g of product (i.e. 67% based on 2-chlorobenzonitrile) are obtained, m.p. = 113-114.5 ° C. Further product fraction can be obtained by extraction of the aqueous filtrate with toluene. The identity of the substance was confirmed by mass spectroscopy.
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS347288A CS272570B1 (en) | 1988-05-23 | 1988-05-23 | Method of 2-chlorophenylamidohydrazone preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS347288A CS272570B1 (en) | 1988-05-23 | 1988-05-23 | Method of 2-chlorophenylamidohydrazone preparation |
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| Publication Number | Publication Date |
|---|---|
| CS347288A1 CS347288A1 (en) | 1990-05-14 |
| CS272570B1 true CS272570B1 (en) | 1991-02-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS347288A CS272570B1 (en) | 1988-05-23 | 1988-05-23 | Method of 2-chlorophenylamidohydrazone preparation |
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1988
- 1988-05-23 CS CS347288A patent/CS272570B1/en unknown
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| CS347288A1 (en) | 1990-05-14 |
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