Next Article in Journal
Principal Component Regression Analysis of the Relation Between CIELAB Color and Monomeric Anthocyanins in Young Cabernet Sauvignon Wines
Next Article in Special Issue
Mechanistic Study of the Spiroindolones: A New Class of Antimalarials
Previous Article in Journal
Microwave Accelerated Aza-Claisen Rearrangement
Previous Article in Special Issue
Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Synthesis and Structure of New 3,3,9,9-Tetrasubstituted-2,4,8,10-Tetraoxaspiro[5.5]undecane Derivatives

1
Organic Chemistry Department and CCOCCAN, Babes-Bolyai University, Cluj-Napoca, 11 Arany Janos str., 400028, Cluj-Napoca, Romania
2
IRCOF, UMR 6014, Université de Rouen, 76821 Mont Saint-Aignan, Cedex, France
3
Organic Chemistry Department, University of Debrecen, P.O. Box 20, 4010 Debrecen, Hungary
*
Author to whom correspondence should be addressed.
Molecules 2008, 13(11), 2848-2858; https://doi.org/10.3390/molecules13112848
Submission received: 8 August 2008 / Revised: 12 October 2008 / Accepted: 12 November 2008 / Published: 17 November 2008
(This article belongs to the Special Issue Spiro Compounds)

Abstract

:
The configurational and conformational behavior of some new 3,3,9,9-tetra-substituted-2,4,8,10-tetraoxaspiro[5.5]undecane derivatives with axial chirality was investigated by conformational analysis and variable temperature NMR experiments.

Introduction

The stereochemistry of spiranes with six-membered rings has been extensively studied [1]. Most of these investigations were carried out with spiranes containing 1,3-dioxane units [1,2,3,4,5,6,7,8,9,10]. The chirality of the parent spiro[5.5]undecane (1, Scheme 1) was observed by Dodziuk [3,4], but at that time no chiral element according to the classification of Cahn, Ingold and Prelog [11,12] was found and the chirality of the spiro compounds with six-membered rings could not be satisfactorily explained. Later, we observed the possibility of the helical arrangement in polyspiranes with six-membered rings [5,6]. In these polyspiranes the helix can become identical with itself after each fourth six-membered ring. In monospiranes (e.g. compound 1) the helix begins to be built and the two enantiomeric structures exhibit either P or M configuration (Scheme 1).
Scheme 1. Helical structure of spiro[5.5]undecane (1).
Scheme 1. Helical structure of spiro[5.5]undecane (1).
Molecules 13 02848 g004
On the other hand the axial chirality of these spiranes is also different. For instance, the semiflexible derivatives 2 of 1,5-dioxaspiro[5.5]undecane (Scheme 2) with helical chirality (as a result of the specific arrangement of the spirane skeleton) exhibit axial chirality too, despite the similar substituents located at one of the ends (position 3) of the spirane [5,6] system.
Scheme 2. Axial chirality of semiflexible spiranes with 1,5-dioxaspiro[5.5]undecane skeleton.
Scheme 2. Axial chirality of semiflexible spiranes with 1,5-dioxaspiro[5.5]undecane skeleton.
Molecules 13 02848 g005
The C6-C9 axis is a chiral element and the different groups at the ends of this axis are R and H at C9 and the 1,3-dioxane ring on one side and the missing ligand on the other side at C6. In these compounds (2) the carbocycle is anancomeric and the heterocycle is flipping. This conformational equilibrium (flipping of the heterocycle) is an enantiomeric inversion (Scheme 2).
Compounds with 2,4,8,10-tetraoxaspiro[5.5]undecane skeleton (3, Scheme 3) bearing different substituents at both ends of the spirane system were also investigated. In these compounds, besides the helical chirality, two chiral axis (C3-C6 and C6-C9) can be considered and six isomers are possible (Table 1) [6,13]. In all studied compounds 3 there are large conformational energy differences between the substituents located at the same positions and the compounds exhibit anancomeric structures. If substituents R and R2 have a considerably higher free energy than the other substituents located at the same positions (R1 and R3) the preferred structures (I and IV) exhibit these groups in equatorial orientations. Structures I and IV are considered representative for compounds 3, they cannot be transformed into one other by conformational processes and thus represent separable enantiomers.
Scheme 3. Main conformers of tetrasubstituted anancomeric spiranes with 2,4,8,10-tetra-oxaspiro[5.5]undecane skeleton.
Scheme 3. Main conformers of tetrasubstituted anancomeric spiranes with 2,4,8,10-tetra-oxaspiro[5.5]undecane skeleton.
Molecules 13 02848 g006
Table 1. Possible stereoisomers for the monospirane with two chiral axes and helical chirality.
Table 1. Possible stereoisomers for the monospirane with two chiral axes and helical chirality.
IsomerConfiguration of the helixConfiguration of chiral axesOrientation of the bulky substituents
C3-C6C6-C9C3 (R)C9 (R2)
IMaSaSeqeq
IIPaRaSaxeq
II’*PaSaReqax
IIIMaRaRaxax
IVPaRaReqeq
VMaSaRaxeq
V’*MaRaSeqax
VIPaSaSaxax
*Because similar substitutions at C3 and C9 structures II and II’; V and V’ are equivalent.
We considered of interest to investigate the stereochemistry (conformational analysis and enantiomerism) of 3,3,9,9-tetrasubstituted-2,4,8,10-tetraoxaspiro[5.5]undecane derivatives with different substituents at the same position (similar to compounds 3) which exhibit flexible structures.

Results and Discussion

New spiro compounds with 2,4,8,10-tetraoxaspiro[5.5]undecane skeleton 4-8 were obtained by the condensation of pentaerythritol with non-symmetrical ketones (Scheme 4).
Scheme 4. Synthesis of spiranes 4-8.
Scheme 4. Synthesis of spiranes 4-8.
Molecules 13 02848 g007
In previous studies [14,15] it was demonstrated that CH3 and CH2X groups located in the ketal part of the 1,3-dioxane ring (position 2) have very close conformational free enthalpies and 2-CH3,2-CH2X-1,3-dioxane derivatives are flexible compounds (Scheme 5) and conformers VII and VIII have similar contributions to the average structure of the compound.
Scheme 5. Conformational equilibria for 2,2-disubstituted-1,3-dioxane derivatives.
Scheme 5. Conformational equilibria for 2,2-disubstituted-1,3-dioxane derivatives.
Molecules 13 02848 g008
Taking into account these data compounds 4-8 were considered flexible. They exhibit (like compounds 3) six conformers (Table 1). These conformers form two groups [I, II (II’), III and IV, V (V’), VI] involved in the equilibria I⇆II(II’)⇆III and IV⇆V(V’)⇆VI (Scheme 6 and Scheme 7).
Scheme 6. Conformational equilibria involving diastereomeric structures I-III.
Scheme 6. Conformational equilibria involving diastereomeric structures I-III.
Molecules 13 02848 g009
Scheme 7. Conformational equilibria involving diastereomeric structures IV-VI.
Scheme 7. Conformational equilibria involving diastereomeric structures IV-VI.
Molecules 13 02848 g010
The conformers of each group are diastereoisomers [ee, ae(ea), aa; CH2X is taken as reference] and they have an enantiomer in the other group. To transform a structure of one group into a structure of the other group it is necessary to break bonds and to remake bonds. Compounds 4-8, despite their flexible structure, exhibit separable enantiomers. In order to discriminate the enantiomers, chiral HPLC experiments, using a CHIRALCEL OD column and normal and chiral (OR) detections, were run with compounds 5 and 8. The peaks of the enantiomers are baseline separated (trs for 5: 27.34, 33.05 min and for 8: 11.6, 13.9 min; Figure 1), but the signals in CD detection are weak probably because these ones are the average of similar contributions belonging to diastereoisomers (see scheme 6 and scheme 7) with opposite optical activity.
Figure 1. HPLC chromatograms of 8 on Chiralcel OD column using UV (211 nm) and OR detection.
Figure 1. HPLC chromatograms of 8 on Chiralcel OD column using UV (211 nm) and OR detection.
Molecules 13 02848 g001
The flexible structure of the compounds was revealed by dynamic 1H- and 13C-NMR experiments. The room temperature (rt) 1H-NMR spectrum exhibits for the three diastereoisomers of the compounds only one set of signals at mean values of the chemical shifts.
For instance the spectrum of 4 run in Et2O-d10 at 283 K (Figure 2, A) shows unique signals (singlets) for the protons of the heterocycles [δ1(11) = 3.68 (the beginning of an AB splitting is observed) and δ5(7) = 3.75 ppm] and for those of the substituents located at positions 3 and 9 [δ(OCH3) = 3.59, δ(CH2) = 2.73 and δ(CH3) = 1.08 ppm]. Despite the flexible structure of the compound, positions 1,11 and 5,7 are diastereotopic and give different signals, so they are not rendered equivalent by conformational equilibria. The rt spectrum of 4 run in C6D6 reveals the diastereotopicity of protons located at the same position (one is procis and the other one is protrans referred to the substituent with higher precedence located at the closer extremity of the spirane skeleton) so in this case the pattern of the spectrum for the protons of the spirane skeleton consists of two AB systems (Figure 2, D).
Figure 2. 1H-NMR experiments run with compound 4 [diethylether-d10: 283 K (A), 203 K (B), 173 K (C); benzene-d6: rt (D)]; *The water signal is moving to higher δ values by diminishing the temperature.
Figure 2. 1H-NMR experiments run with compound 4 [diethylether-d10: 283 K (A), 203 K (B), 173 K (C); benzene-d6: rt (D)]; *The water signal is moving to higher δ values by diminishing the temperature.
Molecules 13 02848 g002
The variable temperature 1H-NMR experiment run with 4 reveals the coalescence of the signals (T = 203 K) and at lower temperature separated groups of signals which correspond to the three frozen diastereoisomers and to the axial and equatorial positions of the protons of the spirane and of the groups located at it. The complete assignment of the signals in the low temperature spectrum was not possible, but the evolution of the pattern of the spectra observed by diminishing the temperature clearly shows the freezing of conformational equilibria and the obtaining at low temperature of frozen diastereoisomers in agreement with the structures shown in schemes 6 and 7. The results obtained in the variable temperature 1H-NMR experiments run with the other compounds of this series are similar with those shown for 4.
Variable temperature 13C-NMR experiments (300 – 164 K) were run with compounds 4, 6 and 8 in THF-d8 (Table 2, Figure 3). The coalescence of the signals for 6 was observed at lower temperature (Tc=170 K) in comparison with the results in the 1H-NMR variable temperature experiment run with the same compound in the same conditions.
Table 2. Results (δ, ppm) of the variable temperature 13C NMR experiments run with compounds 4 and 8. #
Table 2. Results (δ, ppm) of the variable temperature 13C NMR experiments run with compounds 4 and 8. #
CompdC3, C9C1, C11; C5, C7C6CO/Car
rt164 K rt164 K* rt164 K rt164 K*
498.9299.15
98.59
64.47
64.42
63.22
63.60
63.87
32.9331.99
32.20
170.03170.43
170.72
8100.39100.09
100.37
64.49
64.54
63.55
63.81
33.28(a) 128.40
(b) 138.13
(a) 128.51
128.87
(b) 137.70
138.89
* These signals belong to C1, C11 the other group of signals belonging to C5, C7 are overlapped at 164 K with the signals of the solvent. # Some of the signals are still in coalescence at 164 K.
Figure 3. Fragments [C3(9) and C6] of the 13C-NMR spectra of compounds 8 (A) and 4 (B) recorded at 298 K and 164 K.
Figure 3. Fragments [C3(9) and C6] of the 13C-NMR spectra of compounds 8 (A) and 4 (B) recorded at 298 K and 164 K.
Molecules 13 02848 g003
For 4 and 8 the coalescences in the 13C-NMR take place at similar or higher temperatures than in 1H-NMR. At low temperature (164 K) the 13C-NMR spectra (Table 2, Figure 3) are more complicated and exhibit many signals suggesting the freezing of the conformational equilibria - instead of each signal recorded at rt two or more signals (with different intensities) belonging to the frozen diastereoisomers appear.
Despite these favorable results the assignment of the signals to each of the frozen diastereoisomers of 4 and 8 was not possible. However, these results prove that at rt conformational equilibria between many distereoisomers (three according to Scheme 6 and Scheme 7) are present. Attempted determinations of X-ray crystal structures by diffraction for 7 and 8 failed. This was considered to be a consequence of the fact that in solid state the compounds are mixtures of all possible diastereoisomers, whose resolution was not possible. The X-ray crystal structures obtained for similar compounds [16] reveal the preference of the six-membered rings for the chair conformation in solid state, too.

Conclusions

Spiro compounds 4-8 bearing groups with similar conformational enthalpies at the ends of the spirane skeleton show flexible structures. The compounds exhibit separable enantiomers and for each enantiomer the flipping of the six membered rings equilibrate three diastereoisomers which are not separable. The flexible structure of the compounds was revealed by variable temperature 1H and 13C NMR experiments and the chiral behavior of the molecules was proved by chiral HPLC discriminations.

Experimental

General

Routine 1H-NMR (300 MHz) and 13C-NMR (75 MHz) spectra were recorded at room temperature in CDCl3 on a Bruker 300 MHz spectrometer, using the solvent line as reference. Variable temperature NMR spectra were recorded on Bruker Avance DMX 500 spectrometer in CD2Cl2, (CD2)4O or (C2D5)2O. Electron impact (70 eV) mass spectra were obtained on Hewlett-Packard MD 5972 GC-MS instrument. GC analyses were performed on a Hewlett-Packard HP 5890 gas chromatograph. A HP-5MS capillary column (30 m x 0.25 mm x 0.33 µm) and helium gas were used for separations.Electrospray ionisation mass spectra ESI (ESI+) were recorded using an Esquire 3000 ion-trap mass spectrometer (Bruker Daltonic GmbH, Bremen, Germany) equipped with a standard ESI/APCI source. HPLC separations were carried out with a Jasco HPLC system on Chiralcel OD column (5 mm, 250 x 4.6 mm equipped with a 50 x 4.6 mm OD guard column) termostated at 25 °C with eluent hexane : isopropanol 9:1 and 1 ml/min flow rate. A JASCO MD-910 multiwavelength detector and a JASCO OR-2090 chiral detector were used for detection. Melting points were measured with a Kleinfeld melting point apparatus and are uncorrected. Thin layer chromatography (TLC) was conducted on silica gel 60 F254 TLC plates purchased from Merck. Preparative column chromatography was performed using PharmPrep 60 CC (40–63 µm) silica gel purchased from Merck. Chemicals were purchased from Aldrich, Merck or Acros and were used without further purification.

General procedure for preparation of 4-8

A mixture of ketone (48 mmol) and pentaerythritol (20 mmol) and catalytic amounts of p-toluene-sulfonic acid (0.1 g) was dissolved in 100−150 mL benzene (compounds 46 and 8) or toluene (compound 7). The reaction mixture was refluxed and the water was removed by azeotropic distillation using a Dean-Stark trap. When 90 % of the theoretical amount of water had been separated, the mixture was cooled to room temperature and the catalyst was neutralized (under stirring over 1 h) with sodium acetate powder in excess (0.3 g). The reaction mixture was washed with water (2 x 100 mL). After drying with anhydrous sodium sulfate, the solvent was removed in vacuo and the crude product was purified by distillation, column chromatography or by crystallization from methanol.
3,9-Dimethyl-3,9-bis(methoxycarbonylmethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane (4). Yield: 57%; colorless oil; Rf = 0.22 (n-hexane / ethyl acetate = 8:2); 1H-NMR: δ/ppm 1.52 [s, 6H, 3(9)-CH3], 2.76 [s, 4H, 3(9)-CH2-CO-], 3.69 [s, 6H, 3(9)-CH2-COOCH3], 3.71-3.81 [overlapped peaks, 8H, 1(11)-CH2-, 5(7)-CH2-];13C-NMR: δ/ppm 21.5 [3(9)-CH3], 32.4 (C6), 42.1 [3(9)-CH2-], 51.7 [3(9)-CH2COOCH3], 63.8 (C1, C5, C7, C11), 98.1 (C3, C9), 169.6 [3(9)-COO-]; MS (EI, 70 eV) m/z (%): 317 (16), 259 (69), 143 (14), 117 (31), 101 (22), 83 (50), 43 (100); Anal. Calcd for C15H24O8 (332.15): C, 54.21; H, 7.28; found: C, 54.47; H, 7.09.
3,9-bis(Ethoxycarbonylmethyl)-3,9-dimethyl-2,4,8,10-tetraoxaspiro[5.5]undecane (5). Yield: 35%; colorless oil; bp 207 ºC/2 mm; 1H-NMR: δ/ppm 1.25 [t, 6H, 3J = 7.1 Hz, 3(9)-COO-CH2CH3], 1.52 [s, 6H, 3(9)-CH3], 2.75 [s, 4H, 3(9)-CH2-CO], 3,77 (overlapped peaks, 8H, 1-CH2, 5-CH2, 7-CH2, 11-CH2), 4.14 [q, 4H, 3J = 7.1 Hz, 3(9)-CH2COO-CH2CH3]; 13C-NMR: δ/ppm 14.0 [3(9)-CH2-COO-CH2CH3] 22.0 [3(9)-CH3], 32.2 (C6), 41.56 [3(9)-CH2-], 60.4 [3(9)-CH2-COOCH2-], 63.7 (C1, C5, C7, C11), 98.0 (C3, C9), 169.1 [3(9)-COO-]; MS (ESI): 383.16 [M + Na+]; MS (EI, 70 eV) m/z (%): 345 (8), 273 (51), 203 (6), 185 (10), 143 (12), 131 (25), 113 (21), 83 (41), 43 (100); Anal. Calcd for C17H28O8 (360.18): C, 56.65; H, 7.83; found: C, 56.38; H, 7.65.
3,9-Dibenzyl-3,9-dimethyl-2,4,8,10-tetraoxaspiro[5.5]undecane (6). Yield: 29%; white solid; mp 97−98 ˚C; Rf = 0.16 (n-hexane); 1H-NMR: δ/ppm 1.29 [s, 6H, 3(9)-CH3], 2.98 [s, 4H, 3(9)-CH2-], 3.63 [d, 2H, 2J = 11.7 Hz, 1(11)-H], 3.72 [d, 2H, 2J = 11.7 Hz, 1(11)-H’], 3.73 [d, 2H, 2J = 11.7 Hz, 5(7)-H], 3.86 [d, 2H, 2J = 11.7 Hz, 5(7)-H’], 7.23−7.31 [overlapped peaks, 10H, 3(9)-CH2-C6H5]; 13C-NMR: δ/ppm 19.7 [3(9)-CH3], 33.0 (C6), 44.4 [3(9)-CH2-], 63.9 (C1, C11), 64.0 (C5, C7), 99.9 (C3, C9), 126.4, 127.9, 130.6 (tertiary aromatic carbon atoms), 136.6 (quaternary aromatic carbon atom); MS (EI, 70 eV) m/z (%): 277 (80), 143 (65), 113 (31), 91 (40), 83 (65), 43 (100); Anal. Calcd for C23H28O4 (368.20): C, 74.97; H, 7.66; found: C, 75.20; H, 7.39.
3,9-bis(Methoxymethyl)-3,9-dimethyl-2,4,8,10-tetraoxaspiro[5.5]undecane (7). Yield: 36%; white solid; mp 66−67 ºC; Rf = 0.40 (dichloromethane / ethyl acetate = 2:1); 1H-NMR: δ/ppm 1.41 [s, 6H, 3(9)-CH3], 3.37-3.39 [overlapped peaks, 4H, 1(11)-CH2], 3.40 [s, 6H, 3(9)-CH2OCH3], 3.64 [s, 4H, 3(9)-CH2-O-], 3.80 [d, 2H, 2J = 11.8 Hz, 5(7)-H], 3.99 [d, 2H, 2J = 11.8 Hz, 5(7)-H’]; 13C-NMR: δ/ppm 17.3 [3(9)-CH3], 32.9 (C6), 59.4 [3(9)-CH2OCH3], 63.6 (C1, C11), 63.7 (C5, C7), 75.9 [3(9)-CH2O-], 98.5 (C3, C9); MS (ESI): 299.14 [M + Na+]; MS (EI, 70 eV) m/z (%): 261 (3), 231 (63), 143 (31), 113 (25), 83 (67), 43 (100); Anal. Calcd for C13H24O6 (276.16): C, 56.51; H, 8.75; found: C, 56.63; H, 8.98.
3,9-bis(Chloromethyl)-3,9-dimethyl-2,4,8,10-tetraoxaspiro[5.5]undecane (8). Yield: 58%; white solid; mp 120−121 ºC; crystallized from methanol; 1H-NMR: δ/ppm 1.47 [s, 6H, 3(9)-CH3], 3.56 [s, 4H, 1(11)-CH2], 3.69 [s, 4H, 3(9)-CH2-Cl], 3.81 [d, 2H, 2J = 11.7 Hz, 5(7)-H], 3.91 [d, 2H, 2J = 11.7 Hz, 5(7)-H’]; 13C-NMR: δ/ppm 18.7 [3(9)-CH3], 32.8 (C6), 47.2 [3(9)-CH2-Cl], 64.0 (C1, C11), 64.1 (C5, C7), 98.4 (C3, C9); MS (EI, 70 eV) m/z (%): 269 (11), 235 (77), 143 (22), 113 (26), 83 (73), 43 (100); Anal. Calcd for C11H18Cl2O4 (284.06): C, 46.33; H, 6.36; Cl, 24.86; found: C, 46.08; H, 6.64; Cl, 25.03.

Acknowledgements

The financial support of this work by CEEX program (grants 2Cex06-11-50 and BIOTECH 97) is acknowledged.

References

  1. Cismaş, C.; Terec, A.; Mager, S.; Grosu, I. Six-membered ring spiranes: carbocycles and heterocycles with oxygen. Curr. Org. Chem. 2005, 9, 1287–1314. [Google Scholar] [CrossRef]
  2. Mursakulov, I. G.; Ramazanov, E. A.; Guseinov, M. M.; Zefirov, N. S.; Samoshin, V. V.; Eliel, E. L. Stereochemical studies-XXV: Conformational equilibria of 2-substituted 1,1-dialkylcyclohexanes. Tetrahedron 1980, 36, 1885–1890. [Google Scholar] [CrossRef]
  3. Dodziuk, H. Conformation analysis of spiranes by the force-field method. Part 1. Chirality and diastereoisomerism of spiro-compounds: spiro[5.5]undecane and derivatives. J. Chem. Soc., Perkin Trans. 2 1986, 249–251. [Google Scholar] [CrossRef]
  4. Dodziuk, H.; Sitkowski, J.; Stefanian, I.; Mursakulov, I. G.; Guseinov, M. M.; Kurbanova, V. A. Conformational analysis of spiranes. Part III. Manifestation of the chirality in the NMR spectra of spirobisdioxanes at low temperature. Struct. Chem. 1992, 3, 269–276. [Google Scholar] [CrossRef]
  5. Grosu, I.; Mager, S.; Plé, G.; Horn, M. Axial and Helical Chirality of Some Spiro-1,3-dioxanes. J. Chem. Soc. Chem. Commun. 1995, 167–168. [Google Scholar] [CrossRef]
  6. Grosu, I.; Mager, S.; Plé, G. Conformational Analysis of Some Spiro and Polyspiro 1,3-Dioxane Compounds with Axial and Helical Chirality. J. Chem. Soc. Perkin Trans. 2 1995, 1351–1357. [Google Scholar] [CrossRef]
  7. Grosu, I.; Mager, S.; Plé, G.; Mesaros, E. Synthesis and Stereochemistry of Some Dispiro-1,3-Dioxanes with Axial and Helical Chirality. Tetrahedron 1996, 52, 12783–12798. [Google Scholar]
  8. Opris, D.; Grosu, I.; Toupet, L.; Plé, G.; Terec, A.; Mager, S.; Muntean, L. Synthesis and Stereochemistry of New tetraspiro-1,3-dioxanes. J. Chem. Soc. Perkin Trans. 1 2001, 2413–2420. [Google Scholar]
  9. Terec, A.; Grosu, I.; Condamine, E.; Breau, L.; Plé, G.; Ramondenc, Y.; Rochon, F. D.; Peulon-Agasse, V.; Opris, D. Pentaspiranes and Hexaspiranes with 1,3-Dioxane or 1,3-Oxathiane Rings: Synthesis and Stereochemistry. Tetrahedron 2004, 60, 3173–3189. [Google Scholar] [CrossRef]
  10. Lemcoff, N. G.; Fuchs, B. Toward Novel Polyacetals by Transacetalation Techniques: Dendrimeric Diacetals. Org. Lett. 2002, 4, 731–734. [Google Scholar] [CrossRef]
  11. Cahn, R. S.; Ingold, C. K.; Prelog, V. Specification of Molecular Chirality. Angew. Chem., Int. Ed. Engl. 1966, 5, 385–415. [Google Scholar] [CrossRef]
  12. Prelog, V.; Helmchen, G. Basic Principles of the CIP-System and Proposals for a Revision. Angew. Chem., Int. Ed. Engl. 1982, 21, 567–583. [Google Scholar] [CrossRef]
  13. Grosu, I.; Mager, S.; Plé, G.; Martinez, R.; Horn, M.; Gavino, R. R. The Stereochemistry of Some New Chiral Brominated Compounds with a 2,4,8,10-Tetraoxaspiro[5.5]undecanic Skeleton. Monatsh. Chem. 1995, 126, 1021–1030. [Google Scholar] [CrossRef]
  14. Anteunis, M. J. O.; Tavernier, D.; Borremans, F. A review on the conformational aspects in the 1,3-dioxane system. Heterocycles 1976, 4, 293–371. [Google Scholar] [CrossRef]
  15. Mesaros, E.; Grosu, I.; Mager, S.; Plé, G.; Farcas, I. The Study on Peculiar Cases of Prostereoisomerism on Some Suitable Flexible 1,3-Dioxane Derivatives. Monatsh. Chem. 1998, 129, 723–733. [Google Scholar]
  16. Khusainov, M. A.; Makarevich, S. S.; Obodovskaya, A. E.; Starikova, Z. A.; Musavirov, R. S. Molecular and Crystal Structure of 3,9-Bis(4-methoxyphenyl)- and Unsubstituted 2,4,8,10-Tetraoxaspiro[5.5]undecanes. Zh. Strukt. Khim. 1988, 29, 154–161. [Google Scholar]
  • Sample Availability: Contact the authors.

Share and Cite

MDPI and ACS Style

Mihiş, A.; Condamine, E.; Bogdan, E.; Terec, A.; Kurtán, T.; Grosu, I. Synthesis and Structure of New 3,3,9,9-Tetrasubstituted-2,4,8,10-Tetraoxaspiro[5.5]undecane Derivatives. Molecules 2008, 13, 2848-2858. https://doi.org/10.3390/molecules13112848

AMA Style

Mihiş A, Condamine E, Bogdan E, Terec A, Kurtán T, Grosu I. Synthesis and Structure of New 3,3,9,9-Tetrasubstituted-2,4,8,10-Tetraoxaspiro[5.5]undecane Derivatives. Molecules. 2008; 13(11):2848-2858. https://doi.org/10.3390/molecules13112848

Chicago/Turabian Style

Mihiş, Alin, Eric Condamine, Elena Bogdan, Anamaria Terec, Tibor Kurtán, and Ion Grosu. 2008. "Synthesis and Structure of New 3,3,9,9-Tetrasubstituted-2,4,8,10-Tetraoxaspiro[5.5]undecane Derivatives" Molecules 13, no. 11: 2848-2858. https://doi.org/10.3390/molecules13112848

Article Metrics

Back to TopTop