PL217355B1 - New substituted of N, N-bis (2-hydroxyethylo)-N'-acylohydrasonoformamide, their application and production method - Google Patents
New substituted of N, N-bis (2-hydroxyethylo)-N'-acylohydrasonoformamide, their application and production methodInfo
- Publication number
- PL217355B1 PL217355B1 PL384174A PL38417407A PL217355B1 PL 217355 B1 PL217355 B1 PL 217355B1 PL 384174 A PL384174 A PL 384174A PL 38417407 A PL38417407 A PL 38417407A PL 217355 B1 PL217355 B1 PL 217355B1
- Authority
- PL
- Poland
- Prior art keywords
- bis
- nitrophenyl
- reaction
- solution
- dmf
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 14
- -1 2-nitrophenyl Chemical group 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- LTMRLZSHHUFQDP-UHFFFAOYSA-N 3,5,6,7a-tetrahydro-2h-[1,3]oxazolo[2,3-b][1,3]oxazole Chemical compound C1COC2OCCN21 LTMRLZSHHUFQDP-UHFFFAOYSA-N 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- LYGGDXLOJMNFBV-UHFFFAOYSA-N 2-nitrobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1[N+]([O-])=O LYGGDXLOJMNFBV-UHFFFAOYSA-N 0.000 description 1
- NQEWXLVDAVTOHM-UHFFFAOYSA-N 3-nitrobenzohydrazide Chemical compound NNC(=O)C1=CC=CC([N+]([O-])=O)=C1 NQEWXLVDAVTOHM-UHFFFAOYSA-N 0.000 description 1
- PKBGHORNUFQAAW-UHFFFAOYSA-N 4-chlorobenzohydrazide Chemical compound NNC(=O)C1=CC=C(Cl)C=C1 PKBGHORNUFQAAW-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- FKZXYJYTUSGIQE-UHFFFAOYSA-N 4-nitrobenzohydrazide Chemical compound NNC(=O)C1=CC=C([N+]([O-])=O)C=C1 FKZXYJYTUSGIQE-UHFFFAOYSA-N 0.000 description 1
- 244000248349 Citrus limon Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229960003350 isoniazid Drugs 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Opis wynalazkuDescription of the invention
Przedmiotem wynalazku są nowe podstawione pochodne N,N-bis(2-hydroksyetylo)-N'-acylohydrazonoformamidu o ogólnym wzorze 1, sposób otrzymywania podstawionych pochodnych N,N-bis(2-hydroksyetylo)-N'-acylohydrazonoformamidu o ogólnym wzorze 1.The subject of the invention is new substituted N, N-bis (2-hydroxyethyl) -N'-acylhydrazonoformamide derivatives of general formula 1, a method for the preparation of substituted N, N-bis (2-hydroxyethyl) -N'-acylhydrazonoformamide derivatives of general formula 1.
Nowymi podstawionymi N,N-bis(2-hydroksyetylo)-N'-acyIohydrazonoformamidu według wynalazku są związki o ogólnym wzorze 1,The new substituted N, N-bis (2-hydroxyethyl) -N'-acylhydrazonoformamide according to the invention are compounds of the general formula I,
w którym:wherein:
11
- R1 oznacza:- R 1 means:
11
R1 oznacza; 2-nitrofenyl, 3-nitrofeny], 4-nitrofenyl, 4-chlorofenyl, 4-pirydyl, 3-(4-benzyloksy)fenylo-2-(tert-butoksykarbonylo)amino propyl, 2 R 1 is; 2-nitrophenyl, 3-nitrophenyl], 4-nitrophenyl, 4-chlorophenyl, 4-pyridyl, 3- (4-benzyloxy) phenyl-2- (tert-butoxycarbonyl) amino propyl, 2
- R2 oznacza H.- R 2 is H.
W drugim aspekcie przedmiotem wynalazku jest sposób otrzymywania nowych podstawionych pochodnych N,N-bis(2-hydroksyetylo)-N'-acylohydrazonoformamidu o ogólnym wzorze 1, w którym:In a second aspect, the invention relates to a process for the preparation of novel substituted N, N-bis (2-hydroxyethyl) -N'-acylhydrazonoformamide derivatives of the general formula I, wherein:
11
- R1 oznacza: 2-nitrofenyl, 3-nitrofenyl, 4-nitrofenyl, 4-chlorofenyl, 4-pirydyl, 3-(4-benzyloksy)fenylo-2-(tert-butoksykarbonylo)amino propyl, 2 - R 1 is: 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-chlorophenyl, 4-pyridyl, 3- (4-benzyloxy) phenyl-2- (tert-butoxycarbonyl) amino propyl, 2
- R2 oznacza H.- R 2 is H.
Sposób według wynalazku otrzymywania podstawionych pochodnych N,N-bis(2-hydroksyety12 lo)-N'-acylohydrazonoformamidu o ogólnym wzorze 1, w którym R1 i R2 mają wyżej podane znaczenie, polega na przedstawionej na schemacie 1, reakcji pomiędzy odpowiednim hydrazydem o ogólnym wzorze 2,The process according to the invention for the preparation of substituted N, N-bis (2-hydroxyethyl) -N'-acylhydrazonoformamide derivatives of the general formula 1, in which R 1 and R 2 are as defined above, consists in the reaction between the appropriate hydrazide and of general formula 2,
R2 R 2
R-C-N-NH2 il 2 ° (2) w którym R1 i R2 mają wyżej podane znaczenie, a 1-aza-4,6-dioksabicyklo[3.3.0]oktanem (ADBO) o wzorze 3.RCN-NH 2 and 1 2 ° (2) wherein R 1 and R 2 are as defined above, and 1-aza-4,6-dioxabicyclo [3.3.0] octane (ADBO) of formula 3.
OH (2) (3) (1)OH (2) (3) (1)
Schemat 1Scheme 1
Reakcję syntezy według wynalazku pomiędzy odpowiednim hydrazydem, a bicyklicznym amidoacetalem prowadzi się w rozpuszczalniku organicznym w temperaturze od pokojowej do temperatury wrzenia mieszaniny reakcyjnej, ale nie wyższej niż 100°C w czasie od 10 minut do 7 dni. KorzystnieThe inventive synthesis reaction between a suitable hydrazide and a bicyclic amidoacetal is carried out in an organic solvent at a temperature from room temperature to the boiling point of the reaction mixture, but not more than 100 ° C, for 10 minutes to 7 days. Favorable
PL 217 355 B1 reakcję prowadzi się w temperaturze od pokojowej do temperatury wrzenia mieszaniny reakcyjnej jednak nie wyższej niż 80°C w czasie od 30 min do 5 dni, a w szczególności w temperaturze nie wyższej niż 60°C w czasie od 3 godzin do 3 dni.The reaction is carried out at a temperature from room temperature to the boiling point of the reaction mixture, however not higher than 80 ° C, for 30 minutes to 5 days, and in particular at a temperature of not more than 60 ° C for 3 hours to 3 days. .
Korzystny wpływ na przebieg reakcji ma mieszanie mieszaniny reakcyjnej.Stirring of the reaction mixture has a beneficial effect on the course of the reaction.
Korzystne jest także prowadzenie reakcji pomiędzy równoważnymi molowo ilościami obu substratów.It is also advantageous to carry out the reaction between equivalent molar amounts of both substrates.
Reakcję syntezy według wynalazku prowadzi się w rozpuszczalnikach organicznych wybranych z grupy: N,N-dialkiloamidy, sulfotlenki, węglowodory aromatyczne, alkohole, nitryle, etery, węglowodory chlorowane lub ich mieszaninach. Korzystne jest prowadzenie reakcji w rozpuszczalnikach wybranych z grupy: DMF, DMSO, metanol, etanol, izopropanol, acetonitryl, diglym, dioksan lub ich mieszaninach. Szczególnie korzystne jest prowadzenie reakcji w DMF lub metanolu.The synthesis reaction according to the invention is carried out in organic solvents selected from the group: N, N-dialkylamides, sulfoxides, aromatic hydrocarbons, alcohols, nitriles, ethers, chlorinated hydrocarbons or mixtures thereof. It is preferable to carry out the reaction in solvents selected from the group: DMF, DMSO, methanol, ethanol, isopropanol, acetonitrile, diglyme, dioxane or mixtures thereof. It is especially preferred to carry out the reaction in DMF or methanol.
Po zakończeniu reakcji produkt wydziela się z mieszaniny reakcyjnej i w zależności od właściwości produktu i jego rozpuszczalności oczyszcza się jedną z następujących metod.After completion of the reaction, the product is separated from the reaction mixture and, depending on the properties of the product and its solubility, it is purified by one of the following methods.
Metoda 1Method 1
Rozpuszczalnik usuwa się przez odparowanie pod zmniejszonym ciśnieniem, a surowy produkt oczyszcza się przez krystalizację, jeżeli jest ciałem stałym lub na kolumnie chromatograficznej, jeżeli jest cieczą.The solvent is removed by evaporation under reduced pressure and the crude product is purified by crystallization if it is a solid or by column chromatography if it is a liquid.
Metoda 2Method 2
Do mieszaniny reakcyjnej dodaje się, w celu wytrącenia surowego produktu, odpowiedni rozpuszczalnik, w którym produkt reakcji jest nierozpuszczalny lub bardzo trudno rozpuszczalny. Wytrącony surowy produkt, ciekły lub stały, oddziela się i oczyszcza przez krystalizację lub na kolumnie chromatograficznej.A suitable solvent is added to the reaction mixture to precipitate the crude product in which the reaction product is insoluble or very sparingly soluble. The precipitated crude product, liquid or solid, is separated and purified by crystallization or by column chromatography.
Do wytrącenia surowego produktu stosuje się rozpuszczalniki wybrane z grupy: pentan, heksan, heptan, eter dietylowy, eter diizopropylowy. Korzystne jest stosowanie do wytrącenia surowego produktu eteru diizopropylowego.For the precipitation of the crude product, solvents selected from the group of pentane, hexane, heptane, diethyl ether and diisopropyl ether are used. It is preferable to use diisopropyl ether for the precipitation of the crude product.
Krystalizację prowadzi się w rozpuszczalnikach wybranych z grupy: alkohole, ketony, estry, etery, nitryle. Korzystnie krystalizację prowadzi się w etanolu, izopropanolu lub acetonitrylu.Crystallization is carried out in solvents selected from the group: alcohols, ketones, esters, ethers, nitriles. Preferably the crystallization is carried out in ethanol, isopropanol or acetonitrile.
Produkty ciekłe oczyszcza się znanymi metodami chromatograficznymi.The liquid products are purified by known chromatographic methods.
Nowe związki o ogólnym wzorze 1, w którym R1 i R2 mają wyżej podane znaczenie znajdują za12 stosowanie, jako produktów pośrednich do syntezy związków o ogólnym wzorze 1, gdzie R1 i R2 mają wyżej podane znaczenie zaś grupa -OH została zastąpiona halogenem lub grupą metanosulfonyloksylową.The new compounds of general formula 1, in which R 1 and R 2 are as defined above, are used as intermediates in the synthesis of compounds of general formula 1, where R 1 and R 2 are as defined above and the -OH group has been replaced with halogen or a methanesulfonyloxy group.
Sposób otrzymywania nowych podstawionych pochodnych N,N-bis(2-hydroksyetylo)-N'-acylohydrazonoformamidu według wynalazku daje początek nowej, prostej metodzie syntezy związków zawierających ugrupowania N,N-bis(2-hydroksyetylo)aminowe, N,N-bis(2-metylosulfonyloksyetylo)aminowe lub N,N-bis(2-halogenoetylo)aminowe, poprzez reakcję odpowiednich związków z bicyklicznym amidoacetalem, jakim jest 1-aza-4,6-dioksabicyklo[3.3.0]oktan (ADBO).The method of obtaining new substituted N, N-bis (2-hydroxyethyl) -N'-acylhydrazonoformamide derivatives according to the invention gives rise to a new, simple method of synthesizing compounds containing N, N-bis (2-hydroxyethyl) amino, N, N-bis ( 2-methylsulfonyloxyethyl) amino or N, N-bis (2-haloethyl) amino by reaction of the appropriate compounds with a bicyclic amidoacetal such as 1-aza-4,6-dioxabicyclo [3.3.0] octane (ADBO).
Wytwarzanie nowych związków według niniejszego wynalazku, przedstawiono w poniższych przykładach, które ilustrują wynalazek lecz nie ograniczają jego zakresu. Strukturę otrzymanych związków potwierdzono przy użyciu spektroskopii jądrowego rezonansu magnetycznego (NMR).The preparation of new compounds of the present invention is illustrated in the following examples which illustrate the invention but do not limit its scope. The structure of the compounds obtained was confirmed by nuclear magnetic resonance (NMR) spectroscopy.
P r z y k ł a d 1P r z k ł a d 1
W kolbie okrągłodennej o pojemności 100 ml wyposażonej w rurkę z bezwodnym chlorkiem wapnia, umieszczono roztwór 3,41 g 4-chlorobenzhydrazydu w 30 ml DMF-u, do którego wkroplono w czasie 15 minut w temperaturze pokojowej, intensywnie mieszając, roztwór 2,30 g ADBO w 5 ml DMF-u. Mieszanie kontynuowano w temperaturze pokojowej przez 3 dni, a następnie roztwór wymieszano z 400 ml Et2O. Wydzielony osad przeniesiono na lejek, przemyto Et2O i wysuszono. Otrzymano 5,49 g N,N-bis(2-hydroksyetylo)-N'-(4-chlorobenzoilo)hydrazonoformamidu, w postaci bezbarwnego, drobnokrystalicznego osadu z wydajnością 87%, o t.t. 158 - 160°C.A solution of 3.41 g of 4-chlorobenzhydrazide in 30 ml of DMF was placed in a 100 ml round-bottom flask equipped with a tube with anhydrous calcium chloride, to which a solution of 2.30 g was added dropwise over 15 minutes at room temperature with vigorous stirring. ADBO in 5 ml DMF. Stirring was continued at room temperature for 3 days and then the solution was partitioned between 400 ml of Et2O. The separated precipitate was transferred to a funnel, washed with Et2O and dried. 5.49 g of N, N-bis (2-hydroxyethyl) -N '- (4-chlorobenzoyl) hydrazonoformamide were obtained in the form of a colorless, fine crystalline solid with a yield of 87%, m.p. 158 - 160 ° C.
1H-NMR (DMSO-d6, ppm) δ 10.78 (s, 1H, CO-NH, zanika po dodaniu D2O), 7.93 (s, 1H, N=CH-N), 7.84 - 7.81 (m, 2H, 2,6-benzen-H), 7.52 - 7.49 (m, 2H, 3,5-benzen-H), 4.89 (s, 2H, 2 x OH, zanika po dodaniu D2O), 3.57 - 3.53 (m, 4H, 2 x CH2-O), 3.32 - 3.29 (m. 4H, 2 x CH2-N); 1 H-NMR (DMSO-d6, ppm) δ 10.78 (s, 1H, CO-NH, disappears upon addition of D2O), 7.93 (s, 1H, N = CH-N), 7.84 - 7.81 (m, 2H, 2 , 6-benzene-H), 7.52 - 7.49 (m, 2H, 3,5-benzene-H), 4.89 (s, 2H, 2 x OH, disappear after addition of D 2 O), 3.57 - 3.53 (m, 4H , 2 x CH 2 -O), 3.32-3.29 (m, 4H, 2 x CH 2 -N);
13C-NMR (DMSO-d6, ppm) δ 160.72, 154.68, 135.42, 133.35, 128.91, 128.29, 59.05, 51.72. 13 C-NMR (DMSO-d6, ppm) δ 160.72, 154.68, 135.42, 133.35, 128.91, 128.29, 59.05, 51.72.
P r z y k ł a d 2P r z k ł a d 2
W kolbie okrągłodennej o pojemności 100 ml zaopatrzonej w rurkę z bezwodnym chlorkiem wapnia, umieszczono roztwór 3,62 g 2-nitrobenzhydrazydu w 50 ml DMF-u, do którego wkroplono w czasie 15 minut w temperaturze pokojowej, intensywnie mieszając, roztwór 2,30 g ADBO w 5 mlIn a 100 ml round-bottom flask equipped with a tube with anhydrous calcium chloride, a solution of 3.62 g of 2-nitrobenzhydrazide in 50 ml of DMF was placed, to which a solution of 2.30 g was added dropwise over 15 minutes at room temperature with vigorous stirring. ADBO in 5 ml
PL 217 355 B1PL 217 355 B1
DMF-u. Roztwór reagentów mieszano w temperaturze pokojowej przez 48 godzin. Następnie roztwór wylano na 400 ml Et2O i odstawiono w chłodne miejsce do wykrystalizowania produktu. Wydzielony osad przeniesiono na lejek, a następnie przemyto Et2O i wysuszono. Otrzymano 5,93 g N,N-bis(2-hydroksyetylo)-N'-(2-nitrobenzoilo)hydrazonoformamidu, w postaci drobnego, pomarańczowego osadu, z wydajnością 94%, o t.t, 145 - 147°C.DMF. The solution of reagents was stirred at room temperature for 48 hours. The solution was then poured onto 400 ml of Et2O and allowed to stand in a cool place until the product crystallized. The separated precipitate was transferred to a funnel, then washed with Et2O and dried. 5.93 g of N, N-bis (2-hydroxyethyl) -N '- (2-nitrobenzoyl) hydrazonoformamide were obtained in the form of a fine orange solid with a 94% yield, mp 145-147 ° C.
1H-NMR (DMSO-d6, ppm) δ 10.81 (s, 1H, CO NH, zanika po dodaniu D2O), 8.03 - 7,49 (m. 4H, 3,4,5,6-benzen-H), 7.81 (s, 1H, N=CH-N), 4.85 (s, 2H, 2 x OH, zanika po dodaniu D2O), 3.54 (s, 4H, 2 x CH2O), 3.30 (s, 4H, 2 x CH2-N); 1 H-NMR (DMSO-d6, ppm) δ 10.81 (s, 1H, CO NH, disappear on addition of D2O), 8.03 - 7.49 (m, 4H, 3,4,5,6-benzene-H), 7.81 (s, 1H, N = CH-N), 4.85 (s, 2H, 2 x OH, disappears upon addition of D2O), 3.54 (s, 4H, 2 x CH2 O), 3.30 (s, 4H, 2 x CH2 -N);
13C-NMR (DMSO-d6, ppm) δ 160.01, 154.36, 149.22, 147.46, 133.42, 130.56, 129.44, 124.07, 58.84, 51.16. 13 C-NMR (DMSO-d6, ppm) δ 160.01, 154.36, 149.22, 147.46, 133.42, 130.56, 129.44, 124.07, 58.84, 51.16.
P r z y k ł a d 3P r z k ł a d 3
W kolbie okrągłodennej o pojemności 100 ml zaopatrzonej w rurkę z bezwodnym chlorkiem wapnia, umieszczono roztwór 3,62 g 3-nitrobenzhydrazydu w 50 ml DMF-u, do którego wkroplono w czasie 15 minut w temperaturze pokojowej, intensywnie mieszając, roztwór 2,30 g ADBO w 5 ml DMF-u. Roztwór reagentów mieszano w temperaturze pokojowej przez 48 godzin. Po zakończeniu reakcji roztwór wylano na 400 ml Et2O wydzielony osad przeniesiono na lejek, a następnie przemyto E2O i wysuszono. Otrzymano 5,45 g N,N-bis(2-hydroksyetylo)-N'-(3-nitrobenzoilo)hydrazonoformamidu w postaci drobnego, żółtego osadu z wydajnością 91%. o t.t. 145 - 147°C.In a 100 ml round-bottom flask equipped with a tube with anhydrous calcium chloride, a solution of 3.62 g of 3-nitrobenzhydrazide in 50 ml of DMF was placed, to which a solution of 2.30 g was added dropwise over 15 minutes at room temperature with vigorous stirring. ADBO in 5 ml DMF. The solution of reagents was stirred at room temperature for 48 hours. After completion of the reaction, the solution was poured into 400 ml of Et2O, the separated precipitate was transferred to a funnel, then washed with E2O and dried. 5.45 g of N, N-bis (2-hydroxyethyl) -N '- (3-nitrobenzoyl) hydrazonoformamide were obtained in the form of a fine yellow solid with a yield of 91%. at mp 145-147 ° C.
1H NMR (DMSO-d6, ppm) δ 11.03 (s, 1H, CO-NH, zanika po dodaniu D2O), 8.64 (t, J = 2.0 Hz, 1H, 2-benzen-H), 8.35 - 8.32, 8.27 - 8.23 (m, m, 1H, 1H, 4,6-benzen-H), 7.96 (s, 1H, N=CH-N), 7.75 (t, J = 8.1 Hz, 1H, 5-benzen-H), 4.87 (s, 2H, 2 x OH, zanika po dodaniu D2O), 3.58 - 3.54 (m, 4H, 2 x CH2-O), 3.34 - 3.30 (m, 4H, 2 x CH2-N); 1 H NMR (DMSO-d6, ppm) δ 11.03 (s, 1H, CO-NH, disappears upon addition of D 2 O), 8.64 (t, J = 2.0 Hz, 1 H, 2-benzene-H), 8.35 - 8.32 , 8.27 - 8.23 (m, m, 1H, 1H, 4,6-benzene-H), 7.96 (s, 1H, N = CH-N), 7.75 (t, J = 8.1 Hz, 1H, 5-benzene- H), 4.87 (s, 2H, 2 x OH, disappear on addition of D 2 O), 3.58 - 3.54 (m, 4H, 2 x CH2-O), 3.34 - 3.30 (m, 4H, 2 x CH 2 -N );
13C-NMR (DMSO-d6, ppm) δ 159.36, 154.78, 147.71, 136.05, 133.43, 125.25, 121.65, 58.92, 13 C-NMR (DMSO-d6, ppm) δ 159.36, 154.78, 147.71, 136.05, 133.43, 125.25, 121.65, 58.92,
51.71.51.71.
P r z y k ł a d 4P r z k ł a d 4
W kolbie okrągłodennej o pojemności 100 ml zaopatrzonej w rurkę z bezwodnym chlorkiem wapnia, umieszczono roztwór 3,62 g 4-nitrobenzhydrazydu w 50 ml DMF-u, do którego wkroplono w czasie 15 minut, w temperaturze pokojowej, intensywnie mieszając, roztwór 2,30 g ADBO w 5 ml DMF-u. Roztwór reagentów mieszano w temperaturze pokojowej przez 48 godzin. Po zakończeniu reakcji roztwór wylano na 400 ml Et2O wydzielony osad przeniesiono na lejek, a następnie przemyto Et2O i wysuszono. Otrzymano 5,45 g N,N-bis(2-hydroksyetylo)-N'-(4-nitrobenzoilo)hydrazonoformamidu w postaci drobnego, cytrynowożółtego osadu z wydajnością 96%, o t.t. 169 - 170°C.In a 100 ml round-bottom flask equipped with a tube with anhydrous calcium chloride, a solution of 3.62 g of 4-nitrobenzhydrazide in 50 ml of DMF was placed, to which a solution of 2.30 was added dropwise over 15 minutes at room temperature with vigorous stirring. g ADBO in 5 ml DMF. The solution of reagents was stirred at room temperature for 48 hours. After completion of the reaction, the solution was poured into 400 ml of Et2O, the separated precipitate was transferred to a funnel, then washed with Et2O and dried. 5.45 g of N, N-bis (2-hydroxyethyl) -N '- (4-nitrobenzoyl) hydrazonoformamide were obtained in the form of a fine lemon yellow solid with a yield of 96%, m.p. 169-170 ° C.
1H-NMR (DMSO-d6, ppm) δ 10.98 (s, 1H, CO-NH zanika po dodaniu D2O), 8.32 - 8.27 (m, 2H, 3,5-benzen-H), 8.05 - 8.00 (m, 2H, 2,6-benzen-H), 7.95 (s, 1H, N=CH-N), 4.85 (s, 2H, 2 x OH, zanika po dodaniu D2O), 3.55 - 3.53 (m, 4H, 2 x CH2-O), 3.33 - 3.29 (m, 4H, 2 x CH2-N); 1 H-NMR (DMSO-d6, ppm) δ 10.98 (s, 1H, CO-NH disappears upon addition of D 2 O), 8.32 - 8.27 (m, 2H, 3,5-benzene-H), 8.05 - 8.00 ( m, 2H, 2,6-benzene-H), 7.95 (s, 1H, N = CH-N), 4.85 (s, 2H, 2 x OH, disappear with addition of D 2 O), 3.55 - 3.53 (m, 4H, 2 × CH 2 -O), 3.33-3.29 (m, 4H, 2 × CH 2 -N);
13C-NMR (DMSO-d6, ppm) δ 159.80, 154.86, 148.58, 140.44, 128.41, 123.43, 58.88, 51.51. 13 C-NMR (DMSO-d6, ppm) δ 159.80, 154.86, 148.58, 140.44, 128.41, 123.43, 58.88, 51.51.
P r z y k ł a d 5P r z k ł a d 5
W kolbie okrągłodennej o pojemności 100 ml zaopatrzonej w rurkę z bezwodnym chlorkiem wapnia, umieszczono roztwór 4,11 g izoniazydu w 50 ml DMF-u, do którego wkroplono w czasie 15 minut w temperaturze pokojowej, intensywnie mieszając, roztwór 2,30 g ADBO w 5 ml DMF-u. Roztwór reagentów mieszano w temperaturze pokojowej przez 48 godzin. Po zakończeniu reakcji roztwór wylano na 400 ml Et2O wydzielony osad przeniesiono na lejek, a następnie przemyto Et2O i wysuszono. Otrzymano 7,25 g N,N-bis(2-hydroksyetylo)-N'-(4-pirydoilo)hydrazonoformamidu w postaci bezbarwnego krystalicznego osadu z wydajnością 96%, o t.t. 139-141°C.A solution of 4.11 g of isoniazid in 50 ml of DMF was placed in a 100 ml round-bottom flask equipped with a tube with anhydrous calcium chloride, to which was added dropwise over 15 minutes at room temperature, a solution of 2.30 g of ADBO in 5 ml of DMF. The solution of reagents was stirred at room temperature for 48 hours. After completion of the reaction, the solution was poured into 400 ml of Et2O, the separated precipitate was transferred to a funnel, then washed with Et2O and dried. 7.25 g of N, N-bis (2-hydroxyethyl) -N '- (4-pyridoyl) hydrazonoformamide were obtained in the form of a colorless crystalline solid with a yield of 96%, m.p. 139-141 ° C.
1H NMR (DMSO-d6, ppm) δ 10.92 (s, 1H, CO-NH, zanika po dodaniu D2O), 8.70 - 8.68 (m, 2H, 3,5-benzen-H), 7.94 (s, 1H, N=CH-N), 7.72 - 7.70 (m, 2H, 2,6-benzen-H), 4.85 (s, 2H, 2 x OH, zanika po dodaniu D2O), 3.55 - 3.53 (m, 4H, 2 x CH2-O), 3.32 - 3.29 (m, 4H, 2 x CH2-N); 1 H NMR (DMSO-d6, ppm) δ 10.92 (s, 1H, CO-NH, disappears upon addition of D 2 O) 8.70 - 8.68 (m, 2H, 3,5-benzene-H), 7.94 (s, 1H, N = CH-N), 7.72 - 7.70 (m, 2H, 2,6-benzene-H), 4.85 (s, 2H, 2 x OH, disappear with addition of D 2 O), 3.55 - 3.53 (m, 4H, 2 × CH 2 -O), 3.32-3.29 (m, 4H, 2 × CH 2 -N);
13C -NMR (DMSO-d6, ppm) δ 159.81, 155.02, 150.04, 141.61, 121.10, 58.87, 51.20. 13 C -NMR (DMSO-d6, ppm) δ 159.81, 155.02, 150.04, 141.61, 121.10, 58.87, 51.20.
P r z y k ł a d 6P r z k ł a d 6
W kolbie okrągłodennej o pojemności 100 ml zaopatrzonej w rurkę z bezwodnym chlorkiem wapnia, umieszczono roztwór 3.86 g N-[1-metoksy-1-okso-3-(4-hydroksyfenylo)propano]-N-(t-butoksy)aminy w 50 ml DMF-u, do którego wkroplono w czasie 15 minut w temperaturze pokojowej, intensywnie mieszając roztwór 1,15 g ADBO w 5 ml DMF-u. Roztwór reagentów mieszano w temperaturze pokojowej przez 48 godzin. Następnie roztwór wylano na 300 ml H2O i odstawiono w chłodne miejsce do wykrystalizowania produktu. Wytrącony osad przeniesiono na lejek, a następnie przemyto H2O i wysuszono. Otrzymano 4,47 g N,N-bis(2-hydroksyetylo)-N'-[3-(4-benzyloksy)fenylo-2-(tertPL 217 355 B1In a 100 ml round bottom flask equipped with a tube with anhydrous calcium chloride, a solution of 3.86 g of N- [1-methoxy-1-oxo-3- (4-hydroxyphenyl) propane] -N- (t-butoxy) amine was placed in 50 ml of DMF to which was added dropwise over 15 minutes at room temperature a solution of 1.15 g of ADBO in 5 ml of DMF with vigorous stirring. The solution of reagents was stirred at room temperature for 48 hours. The solution was then poured into 300 ml of H 2 O and left to stand in a cool place until the product crystallized. The precipitate was transferred to a funnel, then washed with H 2 O and dried. 4.47 g of N, N-bis (2-hydroxyethyl) -N '- [3- (4-benzyloxy) phenyl-2- (tert PL 217 355 B1) were obtained
-butoksykarbonylo)aminopropionylo]hydrazonoformamidu w postaci bezpostaciowego osadu z wydajnością 89%.-butoxycarbonyl) aminopropionyl] hydrazonoformamide in the form of an amorphous solid with a yield of 89%.
1H-NMR (DMSO-d6, ppm) δ 9.22 (s, 1H, CO-NH, zanika po dodaniu D2O), 7.98 (s, 1H, N=CH-N), 7.46 - 7.33 (m, 5H, benzyl-H), 7.18 - 7.14 (m, 2H, 2,6-benzen-H), 6.92 - 6.89 (m,2H, 3,5-benzen-H), 6.85 (s, 1H, NH t-BOC, zanika po dodaniu D2O), 4.99 (s, 2H, Ph-CH2-O), 4.96 (s, 2H, 2 x OH, zanika po dodaniu D2O), 4.09 - 4.02 (m, 1H, CH-CO), 3.58 - 3.54 (m, 4H, 2 x CH2-O), 3.34 - 3.30 (m, 4H, 2 x CH2-N); 2.83 - 2.63 (m, 2Η, O-Ph-CH), 1.30 - 1.22 (m, 9Η, COH3); 1 H-NMR (DMSO-d6, ppm) δ 9.22 (s, 1H, CO-NH, disappears upon addition of D2O), 7.98 (s, 1H, N = CH-N), 7.46 - 7.33 (m, 5H, benzyl -H), 7.18 - 7.14 (m, 2H, 2,6-benzene-H), 6.92 - 6.89 (m, 2H, 3,5-benzene-H), 6.85 (s, 1H, NH t-BOC, disappear after addition of D 2 O), 4.99 (s, 2H, Ph-CH 2 -O), 4.96 (s, 2H, 2 x OH, disappear after addition of D 2 O), 4.09 - 4.02 (m, 1H, CH-CO ), 3.58 - 3.54 (m, 4H, 2 x CH 2 -O), 3.34 - 3.30 (m, 4H, 2 x CH 2 -N); 2.83 - 2.63 (m, 2Η, O-Ph-CH), 1.30 - 1.22 (m, 9Η, COH3);
13C-NMR (DMSO-d6, ppm) δ 168.26, 156.83, 155.10, 154.72, 137.18, 130.26, 130.12, 128.31, 127.58, 127.50, 114.31, 77.86, 69.00, 58.85, 54.73, 51, 64, 28.14. 13 C-NMR (DMSO-d6, ppm) δ 168.26, 156.83, 155.10, 154.72, 137.18, 130.26, 130.12, 128.31, 127.58, 127.50, 114.31, 77.86, 69.00, 58.85, 54.73, 51, 64, 28.14.
Claims (5)
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| PL384174A PL217355B1 (en) | 2007-12-28 | 2007-12-28 | New substituted of N, N-bis (2-hydroxyethylo)-N'-acylohydrasonoformamide, their application and production method |
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| PL384174A PL217355B1 (en) | 2007-12-28 | 2007-12-28 | New substituted of N, N-bis (2-hydroxyethylo)-N'-acylohydrasonoformamide, their application and production method |
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| PL217355B1 true PL217355B1 (en) | 2014-07-31 |
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