Карцев В.Г.Избранные методы с-за и модифик. гетероциклов т.1 , 2003
.pdf1,3-Dithiolo[4,5-d]pyrimidines: Synthesis and properties
Neilands O.
Riga Technical University, Department of Chemistry 14/24 Azenes str., Riga, LV-1048 Latvia
e-mail: neilands@ktf.rtu.lv
Introduction
A novel heterocyclic system, 1,3-dithiolo[4,5-d]pyrimidine 1, has been prepared and characterized. We aimed at synthesizing the derivatives of uracil-fused 1,3-dithiol- 2-selones and their use in preparation of strongly electron-donating tetrathiafulvalenes bearing an uracil function. We proposed that uracil-fused tetrathiafulvalenes will be capable of forming strong intermolecular complementary hydrogen bonds like nucleic acid. In this paper, we will overview the synthesis and properties of dioxoand amino- oxo-1,3-dithiolo[3,4-d]pyrimidines as well as of dioxoand aminooxopyrimido-fused tetrathiafulvalenes.
Synthesis of 5,7-dioxo(4H,6H)-1,3-dithiolo[4,5-d]pyrimidine-2-diethylimmonium salts 3
We synthesized uracil-fused 1,3-dithioles [1–3] from the derivatives of barbituric acid. Reaction of 2-diethylaminothiocarbonylthiobarbituric acid 2 with conc. sulfuric acid (at 60°C) was found to yield target heterocyclic system 3. Upon dilution with conc. HCl and acetone, chloride 3 precipitated as colorless crystals (Scheme 1).
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Scheme 1 |
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1. H2SO4, 60°C |
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Et 2. H2O, HX |
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X = HSO4, ClO4, Cl |
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5-Amino-7-oxo(6H)-1,3-dithiolo[4,5-d]pyrimidine-2-diethylimmonium salts
Isocytosine-fused 1,3-dithiole system [4] was synthesized from 5-diethylaminothio- carbonylthio-2-amino(1H,5H)pyrimidine-3,6-dione 4. Cyclisation was performed in conc. sulfuric acid. Upon dilution with aqueous perchlorate, compound 5 was precipitated (in neutral solution) with sodium perchlorate. Solubility of this colorless salt in water is lower than that of salts 3. Salt 5 is well soluble (as a weak base) in dilute acids (Scheme 2).
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357 |
Reaction of the salts of compound 3 with nucleophiles
Just as NH acids (pKa 3.3, in water) [2], compounds 3 are capable (in the presence of base) of intramolecular salt formation giving betaine 10. Colorless betaine is watersoluble. Salts of 3 react with strong nucleophiles (sulfides and selenides) in aqueous solutions to yield (via disclosure of the dithiol ring) unusual derivatives of 4-thiobar- bituric acid 11. These compounds are unstable, and undergo cyclization under the action of strong acids yielding yellow 5,7-dioxo(4H,6H)-1,3-dithiolo[4,5-d]pyrimidine-2-thione (12, X = S) and red selone 12 (X = Se) [1, 3] (Scheme 5). This selone is an important starting material for further syntheses.
Scheme 5
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1.Na2X, H2O
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X = S, Se |
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We observed an unusual condensation of salts of 3 (or betaine 10) with β-dicarbo- nyls 13 (in the presence of base in DMF at 90°C) yielding yellow 5,7-dioxo(4H,6H)-1,3- dithiolo[4,5-d]pyrimidine-2-ylidene diethylmalonate 14a, isopropylidene malonate 14b, dimedone 14c, and indan-1,3-dione 14d (Scheme 6). These compounds are NH acids and are capable of salt formation [7].
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Scheme 6 |
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R = OEt (a); R+R = OCMe2O (b), CH2CMe2CH2 (c), |
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Генеральный спонсор и организатор – InterBioScreen Ltd. |
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359 |
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Scheme 9 |
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1. H2SO4, 60°C |
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2. H2O, HClO4 |
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Na2Se |
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Transformations of 5,7-dioxo(4H,6H)-1,3-dithiolo[4,5-d]pyrimidine-2-one (9) [6]
Dithiolone 9 containing polarized S–CO bonds can readily react with strong bases. Reaction of compound 9 with sodium methoxide resulted in dimercaptide methylation of which gave 5,6-di(methylthio)uracil 23. Reaction of dimercaptide with nickel salt and tetrabutylammonium chloride resulted in interesting deep colored dithiolene complex 24 (Scheme 10).
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Scheme 10 |
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4Na+ |
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23 |
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1. NiCl2 |
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2. Bu4NCl |
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Генеральный спонсор и организатор – InterBioScreen Ltd. |
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361 |
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30a,d
R = Me (a), SMe (b); R+R = SCH2CH2S (c), OCH2CH2O (d)
Cross coupling of selone 26 with disubstituted 1,3-dithiol-2-selones resulted in disubstituted 4-amino-6-oxo(5H)pyrimidoTTFs 31a, b. Low-soluble selones were purified upon oxidation with insoluble betaine cation radicals 32a, b followed by reduction [19, 20] (Scheme 13). Betaines possess unusually high electroconductivity (single-component organic conductors [13, 19]). The chemical and electrophysical properties of dioxoand aminooxopyrimidoTTFs have been reviewed in [21, 22].
Scheme 13
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1. Silylation |
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2. 27a, b, Ph3P |
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DMF, |
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N |
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R = Me (a); R+R = OCH2CH2O (b) |
H2N |
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References
1.Tilika V.Zh., Khodorkovskii V.Yu., Neiland O.Ya., USSR Inventor's Certificate 1 738 810.
2.Neiland O.Ya., Zagorskaya N.N., Khim. Geterotsikl. Soedin. 1992 (3) 416.
Генеральный спонсор и организатор – InterBioScreen Ltd. |
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Синтез и химические свойства оксазолидин-4,5-дионов
Некрасов Д.Д.
Пермский госуниверситет 614600, Пермь, ул. Букирева, 15
Оксазолидин-4,5-дионы активно изучаются с конца 50-х годов прошлого века. Наличие в структуре этих соединений двух гетероатомов в значительной степени отличает их химические свойства от свойств других гетероаналогов (тетрагидро- фуран-2,3-дионов, пирролидин-2,3-дионов).
Преобладающее количество методов синтеза оксазолидин-4,5-дионов 1 и 2 основано на реакции оксалилхлорида с различными амидами или имидами в присутствии акцепторов хлористого водорода. Значительно реже для синтеза оксазолидиндионов используются мочевины и основания Шиффа. Конденсированные оксазолидин-4,5-дионы 3 и 4 получают взаимодействием фенилэтиламидов с оксалилхлоридом или орто-аминотиопроизводных пиридина с эфирами β-галоген- α,γ-дикетокислот, соответственно.
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R''' |
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X R |
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R |
R |
R' |
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R' |
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N R' |
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N R'' |
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N |
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R |
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R'' |
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Наиболее характерными для оксазолидин-4,5-дионов являются реакции дециклизации, рециклизации и деструкции оксазолидинового цикла. Некоторые 2-метиленоксазолидин-4,5-дионы 2 могут использоваться в синтезе замещенных ацетилизоцианатов, а конденсированные оксазолидиндионы 3 в синтезе дегидроизохинолинов. Приводятся литературные данные об использовании замещенных оксазолидиндионов в синтезе биологически активных соединений.
Работа выполнена при финансовой поддержке РФФИ (грант № 01-03-32641).
Доклад сделан по материалам обзора, полный текст которого опубликован: в кн. "Избранные методы синтеза и модификации гетероциклов", под ред.
Карцева В.Г., М.: IBS PRESS, 2003, т. 2, с. 396.
Генеральный спонсор и организатор – InterBioScreen Ltd. |
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