TR201617155A2 - Method for the production of 3-bromobenzaldehyde-containing hydrazone derivative with antioxidant activity - Google Patents
Method for the production of 3-bromobenzaldehyde-containing hydrazone derivative with antioxidant activity Download PDFInfo
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- 150000007857 hydrazones Chemical class 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 title abstract description 7
- 230000003078 antioxidant effect Effects 0.000 title description 9
- 230000036542 oxidative stress Effects 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 230000032683 aging Effects 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- -1 phenylcarbamoyl Chemical group 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 10
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 claims description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 7
- SHQNGLYXRFCPGZ-UHFFFAOYSA-N ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound CCOC(=O)CC1=CSC(N)=N1 SHQNGLYXRFCPGZ-UHFFFAOYSA-N 0.000 claims description 6
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
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- 230000015572 biosynthetic process Effects 0.000 abstract description 5
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- 230000000069 prophylactic effect Effects 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- 239000003963 antioxidant agent Substances 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
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- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 5
- 229960003987 melatonin Drugs 0.000 description 5
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- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- IJVJAYYSOBXLJH-UHFFFAOYSA-N NNC(CC1=CSC(NC(NC2=CC=CC=C2)=O)=N1)=O Chemical compound NNC(CC1=CSC(NC(NC2=CC=CC=C2)=O)=N1)=O IJVJAYYSOBXLJH-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 239000000047 product Substances 0.000 description 3
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 2
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- 229960004132 diethyl ether Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- QFRSUAYVIOTVCF-UHFFFAOYSA-N ethyl 2-[2-(phenylcarbamoylamino)-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NC(=O)NC=2C=CC=CC=2)=N1 QFRSUAYVIOTVCF-UHFFFAOYSA-N 0.000 description 2
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- 150000003141 primary amines Chemical class 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Buluş, insan vücudunun ve zihninin yaşlanmasından ve çeşitli hastalıklardan sorumlu tutulan oksidatif strese yönelik koruyucu ilaç hammaddesi olarak kullanılmak üzere; 3-bromobenzaldehit içeren, yeni bir hidrazon türevinin sentezlenmesine ilişkin yöntem ile ilgilidir.The invention is for use as a prophylactic pharmaceutical raw material for oxidative stress, which is held responsible for the aging of the human body and mind and for various diseases; It relates to a process for the synthesis of a novel hydrazone derivative containing 3-bromobenzaldehyde.
Description
TARIFNAME Antioksidan aktiviteye sahip 3-bromobenzaldehit içeren hidrazon türevinin üretimine iliskin yöntem Teknik Alan Bulus, insan vücudunun ve zihninin yaslanmasindan ve çesitli hastaliklardan sorumlu tutulan oksidatif strese yönelik koruyucu ilaç hammaddesi olarak kullanilmak üzere bir hidrazon türevinin üretimine iliskin yöntem ile ilgilidir. DESCRIPTION Production of hydrazone derivative containing 3-bromobenzaldehyde with antioxidant activity method Technical Area The invention is responsible for the aging of the human body and mind and various diseases. a hydrazone to be used as a raw material for protective drug against oxidative stress relates to the method for the production of the derivative.
Bulus özellikle, 3-bromobenzaldehit içeren, yeni bir hidrazon türevinin sentezlenmesine iliskin yöntem ile ilgilidir. In particular, the invention relates to the synthesis of a novel hydrazone derivative containing 3-bromobenzaldehyde. relates to the method.
Teknigin Bilinen Durumu Serbest radikaller, vücudumuzda besinlerin oksijenkullanarak enerjiye çevrilmesi sirasinda olusan metabolik yan ürünlerdir. Serbest radikaller (reaktif oksijen türleri) kararsiz bir yapidadirlar ve kararli hale gelmek için hücrelere saldirarak hasar olusturmaktadirlar. State of the Art Free radicals are produced in our body during the conversion of food into energy using oxygen. are metabolic by-products. Free radicals (reactive oxygen species) are an unstable They are in structure and cause damage by attacking cells to become stable.
Antioksidanlar serbest radikalleri etkisiz hale getirerek hücreleri bu hasarlardan korumaktadirlar. Antioxidants neutralize free radicals and protect cells from these damages. they protect.
Serbest radikaller ve antioksidanlar vücutta dengede olmalidir ki, antioksidanlar serbest radikalleri etkisiz hale getirebilsin. Eger serbest radikal seviyesi, antioksidan seviyesine göre artar ise serbest radikaller hücrelerde oksidatif hasarlara yol açmakta ve bu duruma oksidatif stres denmektedir. Free radicals and antioxidants must be in balance in the body so that antioxidants are free. to neutralize radicals. If the free radical level is relative to the antioxidant level, If it increases, free radicals cause oxidative damage in cells and this situation leads to oxidative damage. called stress.
Oksidatif stres bir hastalik degildir, ancak hastaliga yol açabilecek ya da hizlandiracak bir etkendir. Genellikle koruyucu saglik önlemleri için önemli bir uyarandir. Fakat tehlikeli olan oksidatif stresin herhangi bir semptomunun olmamasidir. Bu durum tespit edilemez ve düzeltilemezse ciddi saglik sorunlarina ve hastaliklara neden olabilir. Toksin ya da patojenlere maruz kalmak, zayif antioksidan defans sistemi, düzensiz yasam sekli, asiri yogun egzersiz ve günlük metabolik ürünler, oksitadif strese neden olmaktadir. Oxidative stress is not a disease, but a condition that can cause or accelerate the disease. is a factor. It is often an important stimulus for preventive health measures. But the dangerous the absence of any symptoms of oxidative stress. This situation cannot be detected and If left uncorrected, it can cause serious health problems and illness. toxin or exposure to pathogens, weak antioxidant defense system, irregular lifestyle, excessive Intense exercise and daily metabolic products cause oxidative stress.
Insan organizmasi enzimatik ve non-enzimatik birçok antioksidan yardimi ile bu zararli etkilerden korunmaya çalismaktadir. Ancak günümüz kosullarindaki endüstriyel gelismeler, sehir hayati ve çevresel kirlilik faktörleri organizmanin bu koruma silahlarini yetersiz birakmakta ve birçok durumda disaridan takviye antioksidan madde kullanimina gerek görülmektedir. With the help of many enzymatic and non-enzymatic antioxidants, the human organism trying to avoid the effects. However, industrial developments in today's conditions, city life and environmental pollution factors are insufficient for these protection weapons of the organism. and in many cases, the use of external supplemental antioxidants is required. is seen.
Mevcut teknikte bilinen en etkili endojen antioksidan maddelerden biri melatonindir. One of the most effective endogenous antioxidant substances known in the current art is melatonin.
Aktivitesini serbest radikalleri yakalayarak göstermekte olan melatonin molekülü basta hidroksil radikali olmak üzere birçok radikali etkisiz hale getirerek organizmayi korumaktadir. The melatonin molecule, which shows its activity by catching free radicals, is primarily It protects the organism by neutralizing many radicals, including the hydroxyl radical.
Bu güçlü etkisine ragmen melatonin kullanimi birçok durumda yetersiz kalmaktadir. Uzun süreli kullanimi Iibido ve düsük tansiyona neden olmakta, nörolojik, otoimmün, kanser gibi hastaliklara sahip ve alerjisi bulunan kisilerde kullanilamamaktadir. Ayrica çok kisa yari ömrü olmasindan dolayi etki yerine ulasmadan parçalanmakta ve hedef organlara seçici etki gösterememektedir. Despite this strong effect, the use of melatonin is insufficient in many cases. Long Long-term use causes ibido and low blood pressure, neurologic, autoimmune, cancer, etc. It cannot be used in people with diseases and allergies. Also very short half-life It breaks down before reaching the place of action and has a selective effect on target organs. cannot show.
Teknigin bilinen durumunda melatonin gibi indol türevlerinin de antioksidan olarak kullanildigi bilinmektedir. Indol türevleri yüksek rezonans stabilitesine ve halka üzerinde bir çok degisik Sübstitüente sahip heterosiklik aromatik bir halka yapisina sahiplerdir. In the state of the art, indole derivatives such as melatonin are also used as antioxidants. known. Indole derivatives have high resonance stability and many variations on the ring. They have a heterocyclic aromatic ring structure with substituents.
Yapilan in vivo ve in vitro çesitli deneyler sonucunda da birçok melatonin analogu bilesiginin melatoninden daha iyi antioksidan özelliklere sahip olduklarini göstermektedir. As a result of various in vivo and in vitro experiments, many melatonin analogue compounds have been determined. It shows that they have better antioxidant properties than melatonin.
Sonuç olarak yukarida bahsedilen olumsuzluklardan ve eksikliklerden dolayi, ilgili teknik alanda bir yenilik yapma ihtiyaci ortaya çikmistir. As a result, due to the above-mentioned disadvantages and shortcomings, the relevant technical There is a need for innovation in the field.
Bulusun Amaci Mevcut bulus, yukarida bahsedilen gereksinimleri karsilayan, tüm dezavantajlari ortadan kaldiran ve ilave bazi avantajlar getiren antioksidan aktiviteye sahip, 3-bromobenzaldehit içeren hidrazon türevinin üretimine iliskin yöntem ile ilgilidir. Purpose of the Invention The present invention satisfies the above-mentioned requirements, eliminates all disadvantages. 3-bromobenzaldehyde with antioxidant activity that removes It relates to the method for the production of the hydrazone derivative containing
Bulusun öncelikli amaci, insan vücudunun ve zihninin yaslanmasindan ve çesitli hastaliklardan sorumlu tutulan oksidatif strese yönelik koruyucu ilaç olarak kullanilmak üzere hidrazon türevi olan 2-{2-[(fenilkarbamoil)amino]-1,3-tiyazoI-4-il}-[N'-(3-bromofenil)metilen] asetohidrazinin üretilmesidir. The primary aim of the invention is to prevent the aging of the human body and mind and various to be used as a preventive drug for oxidative stress implicated in diseases 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}-[N'-(3-bromophenyl)methylene] production of acetohydrazine.
Bulusun bir amaci, yan etkisi az, sitotoksik etkileri giderilmis yeni bir hidrazon türevinin sentezlenmesidir. One of the aims of the invention is to produce a new hydrazone derivative with little side effects and with no cytotoxic effects. is synthesis.
Bulusun bir diger amaci, serbest radikal yakalama aktivitesi yüksek yeni bir hidrazon türevinin sentezlenmesidir. Another object of the invention is to develop a new hydrazone with high free radical scavenging activity. synthesis of its derivative.
Bulusun bir baska amaci, sentezlenen hidrazon türevinin orijinal bir antioksidan ilaç hammaddesi olarak kullanilmasinin saglanmasidir. Another object of the invention is to make the synthesized hydrazone derivative an original antioxidant drug. to be used as raw material.
Bulusun bir baska amaci, üretim maliyetinin düsük ve üretim asamalarinin kolay olmasidir. Another object of the invention is that the production cost is low and the production steps are easy.
Yukarida anlatilan amaçlarin yerine getirilmesi için bulus, insan vücudunun ve zihninin yaslanmasindan ve çesitli hastaliklardan sorumlu tutulan oksidatif strese yönelik koruyucu ilaç hammaddesi olarak kullanilmak üzere; 0 etil (2-amin0-1,3-tiyazoI-4-il)asetatin diklormetandaki çözeltisine fenilizosiyanatin diklormetandaki çözeltisinin ilave edilmesi ile etiI-2-{2-[(fenilkarbamoil)amin0]-1,3- tiyazoI-4-il}asetatin elde edilmesi, . etil-2-{2-[(fenilkarbam0il)amin0]-1,3-tiyazoI-4-il}asetat bilesiginin metanoldeki çözeltisine %98'Iik hidrazin monohidrat eklenmesi ile 2-{2-[(fenilkarbamoil)amino]-1,3- tiyazol-4-il}asetohidrazitin elde edilmesi, islem adimlarini içeren bir hidrazon türevinin elde edilme yöntemi olup, özelligi; o 2-{2-[(fenilkarbamoil)amino]-1,3-tiyazol-4-il}asetohidrazit bilesiginin etanoldeki çözeltisine 3-br0m0benzaldehit eklenmesi ile 2-{2-[(fenilkarbamoil)amino]-1,3-tiyazol- 4-iI}-[N'-(2-florofenil) metilen]asetohidrazinin elde edilmesi, islem adimini ihtiva etmektedir. In order to fulfill the above-described purposes, the invention involves the human body and mind. Protective against oxidative stress, which is responsible for aging and various diseases to be used as pharmaceutical raw material; 0 ethyl (2-amino-1,3-thiazol-4-yl)acetate solution in dichloromethane with phenylisocyanine ethyl-2-{2-[(phenylcarbamoyl)amino]-1,3- obtaining thiazol-4-yl}acetate, . Ethyl-2-{2-[(phenylcarbam0yl)amino]-1,3-thiazol-4-yl}acetate in methanol by adding 98% hydrazine monohydrate to the solution of 2-{2-[(phenylcarbamoyl)amino]-1,3- obtaining thiazol-4-yl}acetohydrazide, It is a method of obtaining a hydrazone derivative that includes processing steps, and its feature is; o Compound of 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}acetohydrazide in ethanol 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazole- Obtaining 4-yl}-[N'-(2-fluorophenyl)methylene]acetohydrazine, contains the name of the transaction.
Bulusun yapisal ve karakteristik özellikleri ve tüm avantajlari asagida verilen detayli açiklama sayesinde daha net olarak anlasilacaktir ve bu nedenle degerlendirmenin de bu detayli açiklama göz önüne alinarak yapilmasi gerekmektedir. The structural and characteristic features of the invention and all its advantages are described in detail below. will be more clearly understood by means of must be made taking into account the description.
Bulusun Detayli Açiklamasi Bu detayli açiklamada, bulus konusu antioksidan aktiviteye sahip, 3-br0mobenzaldehit içeren hidrazon türevinin üretimine iliskin yöntem, sadece konunun daha iyi anlasilmasina yönelik olarak ve hiçbir sinirlayici etki olusturmayacak sekilde açiklanmaktadir. Detailed Description of the Invention In this detailed description, the subject of the invention is 3-br0mobenzaldehyde containing antioxidant activity. The method for the production of the hydrazone derivative is only intended for a better understanding of the subject. as and without any limiting effect.
Bulus, oksidatif strese yönelik olarak kullanilan koruyucularin yan etkilerinin, mevcut teknikte kullanilan ürünlere nazaran daha düsük, sitotoksik etkileri giderilmis yeni bir hidrazon türevini sentezlenmek üzere; - baslangiç maddesi olan etil-2-{2-[(fenilkarbamoil)amino]-1,3-tiyazoI-4-il}asetati elde etmek üzere; etil (2-amino-1,3-tiyazol-4-il)asetatin diklormetandaki çözeltisine fenilizosiyanatin diklormetandaki çözeltisinin ilave edilmesi, - etil-2-{2-[(fenilkarbamoil)amino]-1,3-tiyazol-4-il}asetat bilesiginin metanoldeki çözeltisine %98'Iik hidrazin monohidrat eklenmesi sonucunda 2-{2- - 2-{2-[(fenilkarbamoil)amino]-1,3-tiyazol-4-il}asetohidrazit bilesiginin etanoldeki çözeltisine 3-br0m0benzaldehit eklenmesi sonucunda nihai ürün olan 2-{2- edilmesi ile ilgilidir. The invention shows that the side effects of preservatives used for oxidative stress can be explained in the current art. A new hydrazone derivative with lower cytotoxic effects compared to the products used. to be synthesized; - obtaining the starting material ethyl-2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}acetate to do; to a solution of ethyl (2-amino-1,3-thiazol-4-yl)acetate in dichloromethane adding a solution of phenylisocyanate in dichloromethane, - ethyl-2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}acetate in methanol As a result of adding 98% hydrazine monohydrate to its solution, 2-{2- - 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}acetohydrazide in ethanol As a result of adding 3-br0m0benzaldehyde to the solution, the final product 2-{2- relates to.
Genel Sentez Yöntemleri 1) Etil-2-{2-[(fenilkarbamoil)amino]-1,3-tiyazoI-4-il}asetat mmol (2.40 9) fenilizosiyanatin 15 mL diklormetandaki çözeltisi ilave edilir ve geri çeviren sogutucu altinda isitilir. Reaksiyon ITK (ince tabaka kramotografisi) ile izlenerek yaklasik 17 saatte bitirilir ve elde edilen karisim süzülüp, diklormetan ile yikanir, kurutulur ve ardindan metanol ile yeniden kristallendirilerek saflastirilir. General Synthesis Methods 1) Ethyl-2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}acetate mmol (2.40 9) of phenylisocyanate solution in 15 mL dichloromethane is added and refluxed. It is heated under the cooler. The reaction was monitored by ITK (thin layer chromatography) for approx. 17 hours and the resulting mixture is filtered, washed with dichloromethane, dried and then Purified by recrystallization with methanol.
Beyaz renkli kristal madde, e.n: 125°C. Su ve petrol eterinde çözünmez. Kloroform, dioksan, metanol, asetonitril, diklorometan, aseton ve etanolde çözünür. Olusan maddenin verimi glementel ALliz (CHNS tayini) 2) 2-{2-[(Fenilkarbamoil)amino]-1,3-tiyazol-4-il}asetohidrazit metanoldeki çözeltisine 39.27 mmol (1.96 g) %98'Iik hidrazin monohidrat eklenir. Reaksiyon karisimi geri çeviren sogutucu altinda 30 dakika isitilir. Reaksiyon tamamlandiktan sonra olusan katilar süzülür, su ile yikanir ve metanol ile yeniden kristallendirilerek saflastirilir. White crystalline substance, m.p.: 125°C. It is insoluble in water and petroleum ether. chloroform, dioxane, It is soluble in methanol, acetonitrile, dichloromethane, acetone and ethanol. The yield of the formed substance glementel ALlysis (CHNS determination) 2) 2-{2-[(Phenylcarbamoyl)amino]-1,3-thiazol-4-yl}acetohydrazide 39.27 mmol (1.96 g) of 98% hydrazine monohydrate is added to its solution in methanol. Reaction The mixture is heated under a refrigeration cooler for 30 minutes. After the reaction is complete The solids formed are filtered, washed with water and purified by recrystallization with methanol.
Beyaz renkli toz madde, en.: 181°C. Su ve dietileterde çözünmez. Kloroform, metanol ve etanolde çözünür. Olusan maddenin verimi %97. glementel Aßliz (CHNS tayini) 3) 2-{2-[(feniIkarbamoil)amino]-1,3-tiyazol-4-il}-[N'-(3-bromofenil)metilen] asetohidrazin etanoldeki çözeltisine 1.50 mmol, 3-br0mobenzaldehit eklenir. Reaksiyon sonucu 2-{2- Reaksiyon karisimi geri çeviren sogutucu altinda 100°C'de 2-3 saat isitilir. Reaksiyon tamamlandiktan sonra karisim sogutulur, elde edilen katilar süzülür ve metanol ile yeniden kristallendirilerek saflastirilir. White powdery substance, mp: 181°C. It is insoluble in water and diethylether. chloroform, methanol and soluble in ethanol. The yield of the resulting substance is 97%. Glementel Aßliz (CHNS determination) 3) 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}-[N'-(3-bromophenyl)methylene] acetohydrazine 1.50 mmol of 3-br0mobenzaldehyde is added to its solution in ethanol. Reaction result 2-{2- The reaction mixture is heated under a refrigeration cooler at 100°C for 2-3 hours. Reaction After completion, the mixture is cooled, the solids obtained are filtered and reconstituted with methanol. crystallized and purified.
Beyaz renkli toz madde, e.n.: 166°C. Su, petrol eteri ve dietileterde çözünmez. Kloroform, metanol ve etanolde kismen çözünür. Olusan maddenin verimi; %48. glementel Aw (CHNS tayini) : Söz konusu bulusta, baslangiç maddesi olarak kullanilan etil (2-amino-1,3-tiyazoI-4-il)asetat grubunun fenilizosiyanat ile reaksiyonu sonucu üre türevi sentezlenmistir. White powdery substance, m.p.: 166°C. It is insoluble in water, petroleum ether and diethylether. Chloroform, Partially soluble in methanol and ethanol. The yield of the resulting substance; 48%. glementel Aw (CHNS determination): In the present invention, ethyl (2-amino-1,3-thiazol-4-yl)acetate is used as starting material. The urea derivative was synthesized as a result of the reaction of the group with phenylisocyanate.
Reaksiyonun olusum mekanizmasi incelendiginde, etil (2-amin0-1,3-tiyazoI-4-il)asetatin amino ucundaki azot atomunun üzerindeki eslesmemis elektronlarin bir diger baslangiç maddesi olan fenilizosiyanattaki karbonil grubundaki (-C=O) karbon atomuna saldirmasi sonucunda, n bagi elektronlari oksijen atomuna göre daha elektronegatif olan azot atomu üzerine açilir ve C=N arasindaki `IT bagi kirilarak karbon ve azot arasinda 0 bagi (C-N) olusur. Böylece etil (2-amino-1,3-tiyazol-4-il)asetatin primer aminin azot atomu pozitif yüklü iken fenilizosiyonattaki azot atomu ise negatif yüklü iyon olusturur. Bunun sonucunda molekül içi proton kaymasi ile negatif yüklü azot atomu, pozitif yüklü diger azot atomundan proton alarak üre türevi bilesik olan Etil 2-{2-[(fenilkarbamoil)amino]-1,3-tiyazoI-4-il} asetat elde edilmistir. When the formation mechanism of the reaction is examined, ethyl (2-amino-1,3-thiazol-4-yl)acetatin Another starting point is the unpaired electrons on the nitrogen atom at the amino end. attack on the carbon atom in the carbonyl group (-C=O) in phenylisocyanate, which is the substance As a result, the nitrogen atom, whose n bond electrons are more electronegative than the oxygen atom, opens on it and the `IT bond between C=N is broken and the 0 bond (C-N) between carbon and nitrogen is created. occurs. Thus, the nitrogen atom of the primary amine of ethyl (2-amino-1,3-thiazol-4-yl)acetate is positively charged. While the nitrogen atom in phenylisocyanate forms a negatively charged ion. As a result of this With an intramolecular proton shift, the negatively charged nitrogen atom is separated from the other positively charged nitrogen atom. Ethyl 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazolyl-4-yl} acetate, which is a urea derivative compound by accepting protons has been obtained.
Reaksiyonun ikinci basamaginda ilk basamakta sentezlenen etil 2-{2-[(fenilkarbamoil)amino]- 1,3-tiyazoI-4-il} asetat hidrazin monohidrat ile muamele edilerek 2-{2-[(fenilkarbamoil)amino]- 1,3-tiyazoI-4-il}asetohidrazit asagidaki mekanizmaya göre sentezlenmistir. In the second step of the reaction, ethyl 2-{2-[(phenylcarbamoyl)amino]-, which is synthesized in the first step, After treatment with 1,3-thiazol-4-yl} acetate hydrazine monohydrate, 2-{2-[(phenylcarbamoyl)amino]- 1,3-thiazol-4-yl}acetohydrazide was synthesized according to the following mechanism.
Reaksiyon mekanizmasi incelendiginde; hidrazinin nükleofilin azot atomu üzerindeki ortaklasmamis elektronlarin etil 2-{2-[(fenilkarbamoil)amino]-1,3-tiyazoI-4-il} asetat bilesiginin ester ucundaki karbonil grubunda bulunan karbon atomuna saldirmasi sonucunda C=O baginin 11 bagi elektronlari karbon atomuna göre daha elektronegatif olan oksijen atomu üzerine açilir ve molekül kararsiz bir geçis halinde bulunur. Daha sonra molekülden etoksi iyonu ayrilir ve C=O bagi tekrar olusur. Sonraki basamakta etoksi grubu hidrazinin karbon atomuyla o bagi olusturan azot atomundaki protonlardan birini koparmasiyla (molekül içi proton aktarimi) yapidan 1 mol etil alkol ayrilarak hidrazit bilesigi olan 2-{2- N î-T-O_ CIIZC1I3 N-C-NÄA H-NLH) îS-L-NH-NHZ Üçüncü basamakta ise; hidrazon türevi bilesiklerin elde edilmesi amaciyla primer amin grubu içeren hidrazit türevi, 3-bromobenzaldehit reaksiyona sokularak karbonil grubuna katilmaktadir. Asit katalizörü kullanilmadan gerçeklestirilen reaksiyonun verimi %40-100 arasinda degismektedir. When the reaction mechanism is examined; hydrazine on the nitrogen atom of the nucleophile of the unshared electrons of ethyl 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl} acetate C=O as a result of attacking the carbon atom in the carbonyl group at the ester end the oxygen atom whose 11 bond electrons are more electronegative than the carbon atom opens on it and the molecule is in an unstable transition state. Then ethoxy from the molecule ion is separated and the C=O bond is formed again. In the next step, the carbon of the ethoxy group hydrazine by removing one of the protons in the nitrogen atom that forms that bond with its atom (intramolecular Proton transfer) 1 mole of ethyl alcohol is separated from the structure and the hydrazide compound 2-{2- N î-T-O_ CIIZC1I3 N-C-NÄA H-NLH) îS-L-NH-NHZ In the third step; primary amine group to obtain hydrazone-derived compounds The hydrazide derivative containing it is reacted with 3-bromobenzaldehyde to the carbonyl group. is participating. The yield of the reaction without the use of acid catalyst is 40-100%. varies between
Reaksiyon mekanizmasina bakildiginda hidrazit yapisinda bulunan uç azot atomu diger azot atomuna göre nükleofilik karakteri daha fazla oldugu için, bu atom üzerindeki serbest elektron çifti, 3-br0m0benzaldehit karbonil grubuna saldirirken C=O baginin TI' elektronlari oksijen Üzerine açilir ve molekül kararsiz ara ürün olan karbinol üre halindeyken azot atomunun pozitif deger almasi ve oksijen atomunun negatif yüklü olmasindan dolayi oksijenin azota ait hidrojenleri koparmasiyla molekülden 1 mol suyun ayrilmasi ile (-N=CH-) azometin grubu olusarak hidrazit-hidrazon türevler elde edilir. ci). N-Ä S H/'\R I _NH_Z\`i:c_R Bulusun özelligi heterosiklik halka tasiyan hidrazon türevi bilesikler, yüksek rezonans stabilitesi ve düsük aktivasyon enerji bariyeri sayesinde serbest radikaller ile reaksiyona girmek için çok uygun bilesiklerdir. Considering the reaction mechanism, the three nitrogen atoms in the hydrazide structure are the other nitrogen atoms. Since it has a more nucleophilic character than the free atom on this atom, TI' electrons of the C=O bond while the electron pair attacks the 3-br0m0benzaldehyde carbonyl group It opens on oxygen, and when the molecule is in the form of carbinol urea, which is an unstable intermediate, nitrogen Because its atom is positive and the oxygen atom is negatively charged. with the removal of 1 mole of water from the molecule by the removal of the hydrogens of the nitrogen by the oxygen (-N=CH-) By forming the azomethine group, hydrazide-hydrazone derivatives are obtained. c). N-Ä S H/'\R I _NH_Z\`i:c_R The feature of the invention is hydrazone derivative compounds carrying heterocyclic rings, high resonance Reacts with free radicals thanks to its stability and low activation energy barrier. They are very suitable compounds to enter.
ISTEMLER 1. Bulus, insan vücudunun ve zihninin yaslanmasindan ve çesitli hastaliklardan sorumlu tutulan oksidatif strese yönelik koruyucu ilaç hammaddesi olarak kullanilmak üzere; a. etil (2-amin0-1,3-tiyazoI-4-il)asetatin diklormetandaki çözeltisine fenilizosiyanatin diklormetandaki çözeltisinin ilave edilmesi ile etiI-2-{2-[(fenilkarbamoil)amin0]-1,3- tiyazoI-4-il}asetatin elde edilmesi, b. etil-2-{2-[(fenilkarbam0il)amin0]-1,3-tiyazoI-4-il}asetat bilesiginin metanoldeki çözeltisine %98'Iik hidrazin monohidrat eklenmesi ile 2-{2-[(feniIkarbamoiI)amino]-1,3- tiyazoI-4-il}aset0hidrazitin elde edilmesi, islem adimlarini içeren bir hidraZOn türevinin elde edilme yöntemi olup, özelligi; c. 2-{2-[(fenilkarbamoil)amino]-1,3-tiyazol-4-il}asetohidrazit bilesiginin etanoldeki çözeltisine 3-br0m0benzaldehit eklenmesi ile 2-{2-[(feniIkarbamoiI)amin0]-1,3-tiyazol- 4-iI}-[N'-(3-bromofenil)metilen] asetohidrazinin elde edilmesi, islem adimini içermesidir. 2. Istem 1'e uygun hidrazon türevinin elde edilme yöntemi olup, özelligi; bahsedilen c basamaginin; 0 geri sogutucu altinda 100°C'de 2 ila 3 saat süreyle isitilmasi, - elde edilen karisimin sogutulmasi, - elde edilen katilarin süzülüp, metanol ile yeniden kristallendirilerek saflastirilmasi, islem adimlarini içermesidir. 3. Istem 1'de bahsedilen üretim yöntemi ile elde edilen ürün, 2-{2-[(fenilkarbamoil)amin0]- 1,3-tiyazoI-4-iI}-[N'-(3-bromofenil)metilen] asetohidrazindir. REQUESTS 1. The invention is responsible for the aging of the human body and mind and various diseases to be used as a protective drug raw material for retained oxidative stress; a. phenylisocyanine to solution of ethyl (2-amino-1,3-thiazol-4-yl)acetate in dichloromethane ethyl-2-{2-[(phenylcarbamoyl)amino]-1,3- obtaining thiazol-4-yl}acetate, b. Ethyl-2-{2-[(phenylcarbam0yl)amino]-1,3-thiazol-4-yl}acetate in methanol by adding 98% hydrazine monohydrate to the solution of 2-{2-[(phenylcarbamoyl)amino]-1,3- obtaining thiazol-4-yl}acet0hydrazide, It is a method of obtaining a hydraZOn derivative that includes processing steps, and its feature is; c. 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazol-4-yl}acetohydrazide in ethanol 2-{2-[(phenylcarbamoyl)amino]-1,3-thiazole- Obtaining 4-yl}-[N'-(3-bromophenyl)methylene] acetohydrazine, It contains the name of the transaction. 2. It is the method of obtaining the hydrazone derivative according to claim 1, its feature is; mentioned c. of the step; Heating at 100°C under 0 reflux for 2 to 3 hours, - cooling of the resulting mixture, - purification of the solids obtained by filtration and recrystallization with methanol, It contains the process steps. 3. The product obtained by the production method according to claim 1, 2-{2-[(phenylcarbamoyl)amino]- 1,3-thiazol-4-yl}-[N'-(3-bromophenyl)methylene] acetohydrazine.
Antioksidan aktiviteye sahip 3-bromobenzaldehit içeren hidrazon türevinin üretimine iliskin yöntem Bulus, insan vücudunun ve zihninin yaslanmasindan ve çesitli hastaliklardan sorumlu tutulan oksidatif strese yönelik koruyucu ilaç hammaddesi olarak kullanilmak üzere; 3-br0mobenzaldehit içeren, yeni bir hidrazon türevinin sentezlenmesine iliskin yöntem ile Production of hydrazone derivative containing 3-bromobenzaldehyde with antioxidant activity method The invention is responsible for the aging of the human body and mind and various diseases. to be used as a protective drug raw material for oxidative stress; By a method for synthesizing a novel hydrazone derivative containing 3-br0mobenzaldehyde
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