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УДК 547.341+547.725
STRUCTURAL DIVERSITY OF 1,3,4,6-TETRACARBONYL
COMPOUNDS, THEIR ANALOGUES
AND NITROGEN CONTAINING DERIVATIVES (REVIEW)
O.G. Karmanova, V.O. Kozminykh, P.P. Mukovoz, E.N. Kozminykh
The article summarizes published data and provides new information concerning the synthesis, structural diversity and properties of 1,3,4,6-tetracarbonyl compounds. Bis-1,3-diketonates are presented in solid state by (E,E)-isomer, and in solutions by dominant (E,E)- and minor (Z,Z)-isomers. Structure peculiarities and mass fragmentation of 1,6-dialkyl-3,4-dihydroxy-2,4-hexadiene-1,6-diones are investigated. Condensation of alkyl methyl ketones with diethyl oxalates and
1,2-diaminobenzene results in 2,3-Ais-(2-oxoalkylidene)tetrahydro-1,2,3,4-quinoxa-lines. With the help of spectral methods isomeric forms of synthesized compounds are found. Compounds containing contiguous 1,2- and 1,3-dioxo fragments look promising for fine organic synthesis and structural chemical analysis.
Ключевые слова: alkyl methyl ketones, oxalic condensation, 1,6-dialkyl-3,4-dihyd-roxy-2,4-hexadiene-1,6-diones, tautomeric forms, 2,3-bis-oxoylidene-1,3,4,6-tetra-hydroquinoxalines.
For a long time the chemistry of 1,3,4,6-tetracarbonyl compounds (TCC) has remained virtually unexplored. Until recently, there has been a small number of papers concerning TCC that described the synthesis of some 1,6-disubstituted 1,3,4,6-hexanetetraones [1, 2]. TCC and their derivatives are noted for their diverse structure and high reactivity and are convenient to be used as structural blocks for the synthesis of various heterocyclic compounds. TCC (1) are unique bis-P-diketone molecules of which contain maximum contiguous 1,3-dicarbonyl units and are characterized by various physicochemical properties. Certain results of TCC (1) study are given in the papers [3, 4]. In the review of the current state of research into TCC we present the results of our own work. Scheme 1 shows the basic method of TCC (1) preparation used for compound preparative synthesis. The least studied 1,3,4,6-tetracarbonyl systems are 1,6-dialkyl derivatives, structural features of which have not been known before our research.
Published data on 1,6-dialkyl-1,3,4,6-tetraoxohexanes provide concise data on the synthesis of compounds having identical alkyl substituents [5]. TCC (1) (Scheme 1 shows the basic equilibrium structures 1A, 1B, 1C which we take into account) in the solid state are marked by a stabilized intramolecular hydrogen bond (IHB) OH---O=C~ inside two contiguous six-membered OH-chelates [3, 4, 6-12] in the linear 1,6-dioxo-3,4-dienol form 1B. Thus, tetraketones (1) should in fact be regarded as a
1.6-disubstituted 3,4-dihydroxy-2,4-hexadiene-1,6-diones. TCC solutions contain not only tautomer 1B but also appreciable amounts of ring oxofuran equilibrium form 1C [13-15] (Scheme 1). Minor isomers (rated 1A and its derivatives 1D, 1E, 1F) were also found in the NMR 'H spectra, but their amount not exceed 3-5 % [3, 4, 14, 15]. In nonpolar solutions compounds (1) are mainly represented by dioxodienol tautomer 1B, the amount of which always exceeds the sum of the remaining forms if any, and often reaches 100 % [3, 14, 9-12]. In polar solutions tetraketones (1) usually have much larger amount of cyclic tautomer 1C, stabilized by IMB of OH-chelate type [3, 4, 10, 11]. The qualitative dynamic prototropic ring-chain transformations and ring-ring interconversions were thoroughly studied (for compounds (1) with different substituents R1 and R2) in TCC solutions [3, 4, 10, 11]. Operational databases were formed on the basis of NMR :H and mass spectra of 1,3,4,6-tetraoxo systems, some of the results are presented in the publications dated by 2011-2012 [3, 4, 16-18]. The mass-decay processes of tetracar-bonyl compounds with aliphatic substituents induced by electron impact using a chromato-mass spectrometry (Scheme 2) have been studied. The two main dominant directions of fragmentation prevail for
1.6-dialkyl-3,4-dihydroxy-2,4-hexadiene-1,6-diones (1). The first direction Fi involves С(3)О-С(4)О rupture which results in the formation of two equivalent alkanoylacetyl units. The second important trend of the fragmentation is the alkanoyl ion elimination along with the simultaneous formation of ion
F3 [M-Alk1(2)CO]+. The most intense peaks are [RCOCH2CO]+ and [RCO]+, formed by the a-cleavage of bonds in the molecule. The molecular ion in spectra of compounds (1) is always present, its intensity increases notably on transition from lower to higher alkyl substituents.
„Me Eto
Y
Eto li R2 Me
+ У4« + Y
O o
MeONa
2HCl - EtOH -NaCl
O O
RW^r
O O 1 a-d
A
R2(R‘)
2(1)
F
Scheme 1. Synthesis and structural diversity of 1,3,4,6-hexantetraones (1)
1 2
Alk1 и Alk2 = CH3, C2H5, h-C3H7, H-C5Hn, h-C6H13
6 - 100%
F4
1/2M - H +Alk1(2)COCH=C=O+
0,34 - 1,91%
M.
CnH2n-6O4
0,04 - 2,32%
3
CnH2n-5O3
CnH2n-1O
Alk1(2)C^+
9 - 54%
M - Alk1(2)cO = Alk1(2)COCH2COC^| +
6,28 - 15,5%
Scheme 2. Mass fragmentation of compounds (1)
During the one-pot or performed stepwise oxalyl condensation of oxalates with a twofold excess of the similar methyl ketones or equimolar amounts of different methyl ketone substituents R1 and R2 in the presence of bases easily extracted and fairly steady &7's-sodium-1,3-diketonates are formed first [9-11, 19-22] (Scheme 3). The latter if acidified easily turn into the designated dioxo dienols (1). Spectral data
O
2
O
F
2
(IR, NMR) indicate the presence of (Z,Z)-isomer structure 2A with the “aligned” n-bonds in enolates (2) due to the delocalization of electron density in the solution solvation. Solid-state fe-enolates (2) exist in the form of (E,E)-isomer 2B with delocalized double bonds, as evidenced by the intense, broad, relatively low-frequency absorption band in the region at 1605-1655 cm-1 in the IR spectra of compounds (2). Solid-state compounds (2) have an axisymmetric structure along the 3,4-dienolate (2Z,4Z)- 2B bond of C (3)-C(4) and possibly along the isomeric 1,6-dienolate (1Z,5Z)- 2C bond. In some cases, the presence of 1,4-ONa-dienolate (1Z,4Z)- 2D is possible in the solutions [9, 20-22]. Solutions of compounds (2) were recorded to have additional equilibria with (Z,E)- and (E,E)-isomers. For example, the source of such equilibria is isomeric structure (Z,E)- 2E with delocalized double bonds. The most likely (2Z,4E)- 2F-isomer, as well as possible (1Z,5E)- 2G- and (1E,4Z)- 2H-geometric forms here serve as specific structures [9,
20, 21]. The final individual choice in favor of a particular dienolate isomer is now quite difficult, since the amorphous compounds (2) can not be cleaned sufficiently with the desired result, and their dissolution is accompanied by side reactions such as solvolysis.
R1( X).
R2( X)
,CH3 o
AlkO-+ ^^OAlk
o
^H o o
>1(2.
,CH3
2(і)
o
NaH (Na, MeONa) (2 : 1)
^O
H
І: R1(2) =
R
(2Z,4Z)-
1(2)
r2(4 (!Z,5Z)-
aZ,4Z)- O .O
Na
2 D
изомеры 6 А-I [9, 22]
»O
(2Z,4E)-
к2(і)
Na+
Na
2(і)
r1(2
(ІE,4Z)-
O
O
2 H, 2 I: R
Na
1(2) :
6 H
O,
(E,E)-
(2E,4E)
+O Na+ —
(!Z,5E)-
Na
2 G
,O
Ar; [22]
R1(X)
R
Na+
o'
Scheme 3. Synthesis and structure of b/s-sodium 1,3-diketonates (dienolates) (2)
R
R
TCC and ringed oxotautomers (1) are widely used in organic synthesis as highly reactive substrates that are easy to get into a variety of nucleophilic transformations. Thus, the reaction of TCC (1) with
1,2-diaminobenzene leads to the formation of 2,3-bis-oxoylidene derivatives of 1,3,4,6-tetra-hydroquinoxalines (3) [13, 15] (Scheme 4).
1 NaH (MeONa)
2HCl
OH O
O O
метод А O O
EtOH
R1 (2L -Me EtO.
X
O
+
O
у*4“-21
O
O^ ^R
■
R
1(2)
1(2)
,2(1)
O OH
nh2
nh2
O^/R OX
O^^R
O^ ^R
NaH (MeONa) 2 HCl
aNH2 nh2
3 A
O^ ^R
N O H
метод Б
-EtOH
R = Alk, Ar
O' R
3 B
O' "R2
3 C O' ''R-
(R1 = Alk1, R2 = Alk2) 3 D
1
3
4
Scheme 4. Synthesis of 2,3-b/s-(2-oxoylidene)-1,2,3,4-tetrahydroquinoxalines (3)
One-pot alkyl methyl ketone condensation with diethyl oxalate in the presence of sodium methylate in a 2:1 ratio, followed by neutralization and the 1,2-diaminobenzene action was first successfully carried out, as a result of which new bis-(oxoylidene)quinoxalines (3) were extracted (method B). The main advantage of method B is the fact that the process of 2,3-bis-(2-oxoyliden)-1,2,3,4-tetrahydro-quinoxaline (3) extraction is more technologically advanced than in method A and it is the one-stage reaction. The structure of the synthesized quinoxaline derivatives (3) of 1,6-dialkyl-3,4-dihydroxy-
2,4-hexadiene-1,6-diones (1) is determined on the basis of IR and NMR 'H spectroscopy. In polar solvents of the compounds (3) 2B is the dominant and most stable form, stabilized by two NH-chelate cycles. The presence of 3B form is also confirmed by the presence of the signals of two magnetically equivalent N(1,4)H-protons of the predominant isomer 3B bis-chelate fragments in the 5 13.95-14.03 ppm in the NMR :H spectra of compounds (3).
There are signals of equal integral intensity of the two magnetically nonequivalent NH protons of predominant isomer 3B in the NMR :H spectrum of compound (3) which has various alkyl substituents at the acyl units (R1 = Alk1, R2 = Alk2), which is caused by the fact that these units propyl and ethyl fragments have different influences. Maximum NH-proton deschielding should be observed when the carbonyl group NH-chelate fragment carbon atom has maximum positive charge and, therefore, when acyl-unit alkyl substituent has minimum positive inductive effect. The chemical shift of N(1,4)H-proton of the compound (3) isomer 3B is much more high field (5 0.7 ppm), compared with a chemical shift of N(4)H-proton of minor isomers of 3D and 3C. The reason probably lies in larger coupling of the aromatic heterocycle with NH-monochelate fragment of isomers 3C and 3D due to the presence of N(1)=C(2)-endocyclic double bond in comparison with bis--chelate isomers 3B. The greater coupling of NH-chelate
and the aromatic ring leads to the anisotropic deschielding effect increase and to the lower field shift of the NH proton signal.
Thus, 1,3,4,6-tetracarbonyl compounds resulting from the Claisen ester condensation, their analogues and nitrogen-containing derivatives, look promising and are accessible for further study of their physicochemical properties and structural diversity.
References
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2. Claisen, L. Über die Einwirkung des Oxaläthers auf Acetophe / L. Claisen // Berichte. - 1887. -Bd. 20. - P. 2188-2189.
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5. Kozminykh, V.O. Claisen condensation of methyl ketones with dialkyloxalates in the synthesis of biologically active carbonyl compounds (review, part 3) / V.O. Kozminykh, V.I. Goncharov, E.N. Kozminykh // Vestnik. Orenburg State University. - 2007. - No. 5 (69). - P. 138-148. (in Russian)
6. Synthesis and antimicrobial activity of 2-substituted 5-aryl-2,3-dihydro-3-furanones and
1.6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones / V.O. Kozminykh, N.M. Igidov, E.N. Kozminykh et al. // Journal of Pharmaceutical Chemistry. - 1991. - Vol. 25, No. 12. - P. 43-47. (in Russian)
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3.4-dihydroxy-2,4-hexadiene-1,6-diones from 5-aryl-2,3-furandiones / V.O. Kozminykh, L.O. Konshina, N.M. Igidov // J. prakt. Chem. (Chem.-Ztg.). - 1993. - Vol. 335, No. 8. - P. 714-716.
8. 1,3,4,6-tetracarbonyl compounds. 3. Synthesis, structural features and antimicrobial activity of
1.6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones / N.M. Igidov, E.N. Kozminykh, O.A. Sofyina et al. // Chemistry of Heterocyclic Compounds. - 1999. - No. 11. - P. 1466-1475. (in Russian)
9. Kozminykh, V.O. 1,3,4,6-Tetracarbonyl systems. Part 9. Diethyl ketipinate: synthesis, structural features and reaction with 1,2-diaminobenzene / V.O. Kozminykh, P.P. Mukovoz, E.A. Kirillova // Vestnik. Orenburg State University. - 2009. - No. 5. - P. 155-166. (in Russian)
10. Kirillova, E.A. Synthesis, chain tautomerism and ring-chain interconversion of substituted
3.4-dihydroxy-2,4-alkadiene-1,6-diones / E.A. Kirillova, V.O. Kozminykh // Vestnik Uzno-Ural’skogo gosudarstvennogo universiteta. Seriâ, Himiâ. - 2009. - No. 23 (156). - P. 9-15. (in Russian)
11. Synthesis, structural features and tautomerism of 1,6-disubstituted 3,4-dihydroxy-2,4-hexa-diene-1,6-diones / E.A. Kirillova, P.P. Mukovoz, A.N. Vinogradov et al. // Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. - 2011. - Vol. 54, No. 4. - P. 18-22. (in Russian)
12. Mukovoz, P.P. Synthesis and structural features of the 3,4-dihydroxy-1,6-hexanedione acid esters / P.P. Mukovoz, O.N. Dvorskaya, V.O. Kozminykh // Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. - 2011. - Vol. 54, No. 5. - P. 96-100. (in Russian)
13. 1,3,4,6-Tetracarbonyl compounds. IV. The interaction of 3,4-dihydroxy-2,4-hexadiene-
1.6-diones with hydrazine and arylhydrazines / T.M. Shironina, N.M. Igidov, E.N. Kozminykh et al. // Journal of Organic Chemistry. - 2001. - Vol. 37, No. 10. - P. 1555-1563. (in Russian)
14. Kozminykh, V.O. 1,3,4,6-Tetracarbonyl compounds. VI. Synthesis of esters and amides of 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadiene acids / V.O. Kozminykh, N.M. Igidov, Y.S. Kasatkina // Journal of Organic Chemistry. - 2001. - Vol. 37, No. 11. - P. 1604-1609. (in Russian)
15. Kozminykh, V.O. Claisen condensation of methyl ketone with dialkyl oxalates in the synthesis of biologically active carbonyl compounds (review, part 3) / V.O. Kozminykh, V.I. Goncharov, E.N. Kozminykh // Vestnik. Orenburg State University. - 2007. - No. 5 (69). - P. 138-148. (in Russian)
16. New modified method of synthesis of 1,6-dialkyl substituted 3,4-dihydroxy-1,6-hexadiene-
1.6-diones / O.G. Karmanova, S.S. Zykova, P.P. Mukovoz, V.O. Kozminykh // International Scientific Periodical «Modern Fundamental And Applied Researches». - 2011. - No. 3. - P. 106-109. (in Russian)
17. Synthesis and structural features of 1,6-dialkyl substituted 1,3,4,6-tetraoxohexanes / O.G. Karmanova, S.S. Zykova, V.O. Kozminykh, P.P. Mukovoz // Collected works of the V International scientific practical conference «Nauchnoye tvorchestvo XXI veka». Krasnoyarsk. - 2012. - Vol. 3. - P. 264-269. (in Russian)
18. Karmanova, O.G. Synthesis and chromato-mass spectrometry of 1,6-dialkyl-3,4-dihydroxy-
2,4-hexadiene-1,6-diones / O.G. Karmanova, V.O. Kozminykh, P.P. Mukovoz // Collected works of the International scientific practical conference «Voprosy estestvennykh nauk: biologiya, khimiya, fizika», Novosibirsk. - 2012. - P. 95-102. (in Russian)
19. Metal derivatives of p-n-electron-donating polycarbonyl systems with close a- and ß-dioxofragments. Part 1. Reference review / V.O. Kozminykh, E.A. Kirillova, Y.V. Shcherbakov et al. // Vestnik. Orenburg State University. - 2008. - No. 9 (91). - P. 185-198. (in Russian)
20. Metal derivatives of p-n-electron-donating poly carbonyl systems with segmented a- and ß-dioxofragments. Part 2. Synthesis and structure of the sodium enolates of 1,3-dicarbonyl compound oxyderivatives / V.O. Kozminykh , P.P. Mukovoz, E.A. Kirillova et al. // Vestnik. Orenburg State University. - 2009. - No. 1 (95). - P. 128-140. (in Russian)
21. Kirillova, E.A. Synthesis and structural features of the aryl-substituted sodium oxo enolates and bis-1,3-diketonates / E.A. Kirillova, V.O. Kozminykh // The proceedings of the All-Russian scientific practical conference with international participation «Aktual'nye problemy khimii i metodiki eyo prepo-davaniya». Nizhny Novgorod. - 2009. - P. 157-160. (in Russian)
22. Kirillova, E.A. Synthesis and structure of sodium enol derivatives with activated mono- and bis-
1,3-dicarbonyl unit / E.A. Kirillova, V.O. Kozminykh // Collected works of the 10th International conference «Aktual'nye problemy sovremennoy nauki. Estestvennye nauki. Chast 8. Organicheskaya khimiya». Samara. - 2009. - P. 15-19. (in Russian)
Received 19 June 2012
ОСОБЕННОСТИ СТРУКТУРНОГО РАЗНООБРАЗИЯ 1,3,4,6-ТЕТРАКАРБОНИЛЬНЫХ СОЕДИНЕНИЙ, ИХ АНАЛОГОВ И АЗОТСОДЕРЖАЩИХ ПРОИЗВОДНЫХ (ОБЗОР)
Обобщены литературные данные и приводятся новые сведения, касающиеся синтеза, структурного разнообразия и свойств 1,3,4,6-тетракарбонильных соединений. £ис-1,3-дикетонаты в твердом состоянии представлены (£’,£)-изомером, а в растворе преобладающим (Е,Е)- и минорным (2,2)-изомерами. Обсуждаются структурные особенности и масс-фрагментация 1,6-диалкил-3,4-дигидрокси-2,4-гексадиен-
1.6-дионов. Конденсацией алкилметилкетонов с диэтилоксалатом и 1,2-диаминобензолом получены
2,3-бис-(2-оксоалкилиден)тетрагидро-1,2,3,4-тетрагидрохиноксалины. С помощью спектральных методов выявлены изомерные формы полученнх соединений. Соединения, содержащие сближенные 1,2- и 1,3-диоксо-фрагменты, являются перспективными для тонкого органического синтеза и структурного химического анализа.
Ключевые слова: алкилметилкетоны; оксалильная конденсация; 1,6-диалкил-3,4-дигидрокси-1,6-гексадиен-
1.6-дионы; таутомерные формы; бис-1,3-дикетонаты; 2,3-бис-оксоилиден-1,3,4,6-тетрагидрохино-
ксалины
Karmanova Olga Gennadyevna - Postgraduate Student, Chemistry Subdepartment, Orenburg State University. 13, Pobedy Prospect, Orenburg, 460018.
Карманова Ольга Геннадьевна - аспирант, кафедра химии, ГОУ ВПО «Оренбургский государственный университет». 460018, г. Оренбург, пр. Победы, 13.
E-mail: mozgunova_em@mail.ru
Mukovoz Petr Petrovich - PhD (Chemistry), researcher. FSI State Centre of agrochemical service “Oren-burgskii”. 1, Kima st., Orenburg.
Муковоз Петр Петрович - кандидат химических наук, научный сотрудник, ФГУ «Государственный центр агрохимической службы «Оренбургский». г. Оренбург, ул. Кима, 1.
E-mail: mpp27@mail.ru
Koz’minykh Vladislav Olegovich - Dr. Sc. (Chemistry), Professor, Chemistry Subdepartment, Perm State Pedagogical University. 24, Sibirskya, Perm, 614990.
Козьминых Владислав Олегович - доктор химических наук, профессор, кафедра химии, ГОУ ВПО «Пермский государственный педагогический университет». 614990, г. Пермь, ул. Сибирская, 24.
E-mail: kvoncstu@yahoo.com
Koz’minykh Elena Nikolaevna - Dr. of Pharmaceutical Sciences, Professor Chemistry Subdepartment, Perm State Pedagogical University. 24, Sibirskya, Perm, 614990.
Козьминых Елена Николаевна - доктор фармацевтических наук, профессор, кафедра химии, ГОУ ВПО «Перский государственный педагогический университет». 614990, г. Пермь, ул. Сибирская, 24.
E-mail: kvoncstu@yahoo.com
