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Open AccessArticle

The Synthesis of Unsubstituted Cyclic Imides Using Hydroxylamine under Microwave Irradiation

1
Department of Chemistry and Physics, Arkansas State University, State University, AR 72467, USA
2
Department of Chemistry, Morgan State University, Baltimore, MD 21251, USA
*
Author to whom correspondence should be addressed.
Molecules 2008, 13(1), 157-169; https://doi.org/10.3390/molecules13010157
Received: 26 December 2007 / Revised: 21 January 2008 / Accepted: 22 January 2008 / Published: 25 January 2008
(This article belongs to the Special Issue ECSOC-11)

Abstract

Unsubstituted cyclic imides were synthesized from a series of cyclic anhydrides,hydroxylamine hydrochloride (NH2OH·HCl), and 4-N,N-dimethylamino-pyridine (DMAP,base catalyst) under microwave irradiation in monomode and multimode microwaves. Thisnovel microwave synthesis produced high yields of the unsubstituted cyclic imides forboth the monomode (61 - 81%) and multimode (84 - 97%) microwaves.
Keywords: Hydroxylamine·HCl; unsubstituted cyclic imides; DMAP; microwaves. Hydroxylamine·HCl; unsubstituted cyclic imides; DMAP; microwaves.

Introduction

The unsubstituted cyclic imide is an important functionality which has been found to maintain significant biological activity [1,2,3]. The synthesis of unsubstituted cyclic imides either by conventional methods or microwave irradiation is often carried out under harsh conditions thereby increasing byproduct formation [4]. Currently, there are several conventional and microwave techniques to produce unsubstituted cyclic imides. Many conventional syntheses of unsubstituted cyclic imides use the reaction of cyclic anhydrides with reactants including ammonia, urea, formamide, and lithium nitride [5,6,7]. Other conventional reactions catalyze the cyclization of acid-amide functionalities forming unsubstituted cyclic imides. These catalysts include carbonyldiimidazole (CDI), DMAP, and AlCl3 [8,9]. Additional microwave syntheses use the reaction of cyclic anhydrides with urea or thiourea, formamide, benzonitrile, cyanate, thiocyanate, DMAP/ammonium chloride, and ammonium acetate [10,11,12,13,14,15].
The application of microwave technology in many conventional syntheses offers many advantages including increased product yields and decreased reaction times [16,17,18,19]. We wish to report the synthesis of a series of unsubstituted cyclic imides using cyclic anhydrides, NH2OH∙HCl, and DMAP via a novel microwave technique. This novel microwave synthesis produced unsubstituted cyclic imides in good yields within minutes.

Results and Discussion

Microwave Synthesis

The novel syntheses were conducted under microwave irradiation using hydroxylamine hydrochloride, DMAP, and an array of cyclic anhydrides yielding the corresponding unsubstituted cyclic imide. (Scheme 1) [20]. Although modifications of several experimental parameters gave moderate yields of the N-hydroxy cyclic imides (~30 percent), repeated studies found that the unsubstituted cyclic imides were the major products. Increased N-hydroxy cyclic imides yields were identified at lower temperatures and shorter reaction times. These results contradict Sugamoto et al., whoreported that N-hydroxy cyclic imides were synthesized in high yield under similar conditions [20]. The current data supports research done by Consonni et al., which found that cyclic N-hydroxyimides are converted to unsubstituted cyclic imides under basic conditions [21]. Application of this novel microwave technique can be used to synthesize many biologically important molecules including that of streptimidone, a glutarimide antibiotic [22].
Scheme 1. The Synthesis of Unsubstituted Cyclic Imides
Scheme 1. The Synthesis of Unsubstituted Cyclic Imides
Molecules 13 00157 g002
Whereas this novel microwave synthesis produced high yields of the unsubstituted cyclic imides, no definite mechanism has been identified. One possible mechanism for unsubstituted cyclic imide formation is the breakdown of hydroxylamine·HCl into ammonia and water (Scheme 2). Ammonia production then promotes unsubstituted cyclic imide formation. A second possibility is the conversion of cyclic N-hydroximide to the unsubstituted cyclic imide. Unsubstituted cyclic imides formation appears to be enhanced by the addition of a base catalyst and additional heating.
Scheme 2. Possible Mechanisms for the Hydroxylamine and Cyclic Anhydride Synthesis
Scheme 2. Possible Mechanisms for the Hydroxylamine and Cyclic Anhydride Synthesis
Molecules 13 00157 g003

Monomode Microwave Synthesis

The monomode microwave synthesis furnished unsubstituted cyclic imides using hydroxylamine as a source for nitrogen, DMAP, and cyclic anhydrides for the cyclic carbon backbone. The microwave synthesis was done at 150 °C over 5 minutes with a maximum energy output of 300W, producing between 61 and 81 isolated percent yields.
Table 1. Monomode Synthesis of Unsubstituted Cyclic Imides using NH2OH(HCl)/ DMAP.
Table 1. Monomode Synthesis of Unsubstituted Cyclic Imides using NH2OH(HCl)/ DMAP.
NH2OH(HCl)/ DMAP (CEM Discover)
EntryImidesTime (min)Temp (oC)Yield (%)
1 Molecules 13 00157 i001515070
2 Molecules 13 00157 i002515071
3 Molecules 13 00157 i003515061
4 Molecules 13 00157 i004515061
5 Molecules 13 00157 i005515061
6 Molecules 13 00157 i006515081

Multimode Microwave Synthesis

A series of multimode microwave reactions were used to identify a cost effective alternative to the more expensive monomode synthesis. This technique used similar reaction conditions and anhydrides to that of the monomode microwave syntheses. The reaction times ranged from 1 to 3 minutes at full power until the material melted and started to vigorously bubble. Isolated percent yields were between 84 and 97 percent.
Table 2. Multimode Synthesis of Unsubstituted Imides Using NH2OH and DMAP.
Table 2. Multimode Synthesis of Unsubstituted Imides Using NH2OH and DMAP.
NH2OH and DMAP (Multimode)
EntryImidesTime (min)Yield (%)
1 Molecules 13 00157 i0072.6897
2 Molecules 13 00157 i0081.8296
3 Molecules 13 00157 i0091.2096
4 Molecules 13 00157 i0101.5784
Unsubstituted cyclic imides were produced in good yields in both the multimode and monomode microwaves. Slightly higher isolated yields were found in the multimode reactions compared to the monomode result. This variation may stem from energy output differences for the multimode (1100 W) and the monomode (300 W) microwaves.
Crystals isolated from this and previous unsubstituted cyclic imide syntheses were analyzed by single crystal X-ray diffraction generating good structural data for the desired cyclic imide products [23]. Specifically, the unsubstituted cyclic imide 3a,4,5,6,7,7a-hexahydro-1H-isoindole-1,3(2H)-dione (4, Figure 1) was characterized by X-ray diffraction studies [24]. The crystal structure of this compound has previously been reported by Wang and co-workers [25]. Our unpublished crystal data found an unsubstituted cyclic imide bound in the cis position of a well defined cyclohexane ring (R factor = 0.0393).
Figure 1. Molecular Diagram of 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione (4) [24].
Figure 1. Molecular Diagram of 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione (4) [24].
Molecules 13 00157 g001

Experimental

General

The monomode microwave reactions were carried out in a CEM Discover Microwave. Multimode microwave reactions were done in a Kennmore Microwave Oven (Household) Output: 1100 Watts (Frequency: 2450 MHz). All Gas Chromatograph Mass Spectrometry (GC-MS) was performed using a Shimadzu GC-17A and GCMS-QP5050A Labsolutions system. All reagents were purchased from Aldrich Chemical Company and were used without further purification. Since two different methods are described in this article Method 1 will refer to synthesis carried out under monomode conditions, while, Method 2 will refer to synthesis under multimode conditions. Only the GCMS data is given, however unsubstituted cyclic imides data matched that reported earlier [15].
Phthalimide (1): Method 1. Phthalic anhydride (0.20 g, 1.35 mmol), NH2OH·HCl (0.09 g, 1.30 mmol), and DMAP (0.04 g, 0.33 mmol) were thoroughly mixed in a CEM vial with a stirrer. This was capped and heated in a CEM Discover microwave for 5 minutes at 150 oC. This was rapidly cooled to room temperature yielding a dark brown solid. The reaction mixture was dissolved in AcOEt (4 mL) and was washed with distilled water (2 x 2 mL). The organic layer was concentrated to obtain a white solid (0.14 g, 70%); MS m/z 147 (M+) 104, 76, 50.
Phthalimide (1): Method 2. Phthalic anhydride (1.0 g, 6.75 mmol), NH2OH·HCl (0.54 g, 7.7 mmol), and DMAP (0.08 g, 0.65 mmol) were mixed in an 8 mL Teflon capped vial. The mixture was allowed to heat for 4 minutes and 11 seconds at 30 percent power in the multimode microwave and then cooled to room temperature. The sample was dissolved in acetone and flash chromatographed using silica (~30 g) with pure acetone as the mobile phase to obtain a yellow solid. Yield: 0.96 g (97%); MS m/z 147 (M+) 104, 76, 50.
Succinimide (2): Method 1. Succinic anhydride (0.20 g, 2.00 mmol), NH2OH·HCl (0.14 g, 2.0 mmol), and DMAP (0.04 g, 0.33 mmol) were thoroughly mixed in a CEM vial with a stirrer. This was capped and heated in a CEM Discover microwave for 5 minutes at 150 °C. This was rapidly cooled to room temperature yielding a dark brown solid. The reaction mixture was dissolved in AcOEt (4 mL) and was washed with distilled water (2 x 2 mL). The organic layer was concentrated to obtain a white solid (0.14 g, 71%); MS m/z 99 (M+) 56.
Succinimide (2): Method 2. Succinic anhydride (1.0 g, 10 mmol), NH2OH·HCl (0.80 g, 11 mmol), and DMAP (0.12 g, 0.98 mmol) were mixed in an 8 mL Teflon capped vial. The mixture was allowed to heat for 1 minute 49 seconds at full power in the multimode microwave and then cooled to room temperature. The sample was dissolved in acetone and flash chromatographed using silica (~30 g) with pure acetone as the mobile phase to obtain a yellow solid (0.95 g, 96%); MS m/z 99 (M+) 56.
cis-1,2-Cyclobutanedicarboximide (3): Method 1. cis-1,2-Cyclobutanedicarboxylic acid anhydride (0.20 g, 1.59 mmol), NH2OH∙HCl) (0.11 g, 1.58 mmol), and DMAP (0.04 g, 0.33 mmol) were thoroughly mixed in a CEM vial with a stirrer. This was capped and heated in a CEM Discover microwave for 5 minutes at 150 °C. This was rapidly cooled to room temperature yielding a white solid. The reaction mixture was dissolved in AcOEt (4 mL) and was washed with distilled water (2 x 2 mL). The organic layer was concentrated to obtain a white solid (0.12 g, 61%); MS m/z 125 (M+) 82, 54.
cis-1,2-Cyclobutanedicarboximide (3): Method 2. cis-1,2-Cyclobutanedicarboxylic acid anhydride (1.0 g, 7.9 mmol), NH2OH∙HCl (0.63 g, 9.1 mmol), and DMAP (0.10 g, 0.82 mmol) were mixed in an 8 mL Teflon capped vial. The mixture was allowed to heat for 1 minute 12 seconds at full power in the multimode microwave and then cooled to room temperature. The sample was dissolved in acetone and flash chromatographed using silica (~30 g) with pure acetone as the mobile phase to obtain a light brown solid, (0.95 g, 96%); MS m/z 125 (M+) 82, 54.
3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione (4): Method 1. cis-1,2-Cyclohexanedicarbo-xylic acid anhydride (0.20 g, 1.30 mmol), NH2OH∙HCl (0.09 g, 1.29 mmol), and DMAP (0.04 g, 0.33 mmol) were thoroughly mixed in a CEM vial with a stirrer. This was capped and heated in a CEM Discover microwave for 5 minutes at 150 °C. This was rapidly cooled to room temperature yielding a white solid. The reaction mixture was dissolved in AcOEt (4 mL) and was washed with distilled water (2 x 2 mL). The organic layer was concentrated to obtain a white solid (0.12 g, 61%); MS m/z 153 (M+) 125, 99, 82, 67, 54, 41.
3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione (4): Method 2. cis-1,2-Cyclohexanedicarboxylic acid anhydride (1.0 g, 6.5 mmol), NH2OH∙HCl (0.51 g, 7.3 mmol), and DMAP (0.08 g, 0.65 mmol) were mixed in an 8 mL Teflon capped vial. The mixture was allowed to heat for 1 minute 49 seconds at full power in the multimode microwave and then cooled to room temperature. The sample was dissolved in acetone and flash chromatographed using silica (~30 g) with pure acetone as the mobile phase to obtain a white solid (0.83 g, 84%); MS m/z 153 (M+) 125, 99, 82, 67, 54, 41.
Glutarimide (5): Method 1. Glutaric anhydride (0.20 g, 1.75 mmol), NH2OH∙HCl (0.12 g, 1.73 mmol), and DMAP (0.04 g, 0.33 mmol) were thoroughly mixed in a CEM vial with a stirrer. This was capped and heated in a CEM Discover microwave for 5 minutes at 150 °C. This was rapidly cooled to room temperature yielding a dark brown solid. The reaction mixture was dissolved in AcOEt (4 mL) and was washed with distilled water (2 x 2 mL). The organic layer was concentrated to obtain a light brown solid (0.12 g, 61%); MS m/z 113 (M+) 70, 42.
3a,4,7,7a-Tetrahydro-4,7-ethano-1H-isoindole-1,3(2H)-dione (6): Method 1. cis-Bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic acid anhydride (0.10 g, 0.56 mmol), NH2OH∙HCl (0.05 g, 0.72 mmol) and DMAP (0.02 g, 0.16 mmol) were mixed thoroughly in a CEM-sealed vial with a magnetic stirrer. The mixture was heated for 5 min at 150 °C in a CEM Discover microwave powered at 150 W. The sample was then cooled rapidly to 40 °C. The reaction mixture was dissolved in AcOEt (4 mL) and was washed with distilled water (2 x 2 mL). The organic layer was concentrated to obtain a light brown solid (0.08 g, 81 %); MS m/z 177 (M+) 149, 99, 78, 51.

Acknowledgements

The author would like to thank Earl Benjamin for his editorial work.

References and Notes

  1. Rennison, D.; Bova, S.; Cavalli, M.; Ricchelli, F.; Zulian, A.; Hopkins, B.; Brimble, M. A. Synthesis and activity studies of analogues of the rat selective toxicant norbormide. Bioorg. Med. Chem. 2007, 15, 2963–2974. [Google Scholar]
  2. Shoji, A.; Kuwahara, M.; Ozaki, H.; Sawki, H. Modified DNA aptamer that binds the (R)-isomer of a thalidomide derivative with high enantioselectivity. J. Am. Chem. Soc. 2007, 129, 1456–1464. [Google Scholar] [CrossRef] [PubMed]
  3. Nakae, K.; Nishimura, Y.; Ohba, S.; Akamatsu, Y. Migtastatin acts as a muscarinic acetylcholine receptor antangonist. J. Antibiot. 2006, 59, 685–692. [Google Scholar] [CrossRef] [PubMed]
  4. Reddy, P. Y.; Kondo, S.; Toru, T.; Ueno, Y. Lewis Acid and Hexamethyldisilazane-Promoted Efficient Synthesis of N-Alkyl- and N-Arylimide Derivatives. J. Org. Chem. 1997, 62, 2652–2654. [Google Scholar] [CrossRef]
  5. Handley, G. J.; Nelson, E. R.; Somers, T. C. Compounds derived from β-substituted glutaric acids: glutarimides, glutaramic acids, 1,5-pentanediols. Aust. J. Chem. 1960, 13, 127–144. [Google Scholar] [CrossRef]
  6. Polonaski, T.; Milewska, M. J.; Gdaniec, M. Synthesis, structure and chiroptical spectra of the bicyclic α-diketones, imides and dithioimides related to santenone. Tetrahedron: Asymmetry 2000, 11, 3113–3122. [Google Scholar]
  7. Gordon, A. J.; Ehrenkaufer, R. L. E. Chemistry of imides. II. Cyclic imides and some unusual products from some diacid chlorides and lithium nitride. J. Org. Chem. 1971, 36, 44–45. [Google Scholar]
  8. Muller, G. W.; Konnecke, W. E.; Smith, A. M.; Khetani, V. D. A Concise Two-Step Synthesis of Thalidomide. Org. Process Res. Dev. 1999, 3, 139–140. [Google Scholar] [CrossRef]
  9. Bon, E.; Reau, R.; Bertand, G.; Bigg, D. C. H. Aluminum trichloride-promoted aminolysis of cyclic imides and oxazolidinones. Tetrahedron Lett. 1996, 37, 1217–1220. [Google Scholar] [CrossRef]
  10. Seijas, J. A.; Vázquez-Tato, M. P.; González-Bande, C.; Martínez, M. M.; Pacios-López, B. Microwave Promoted Synthesis of a Rehabilitated Drug: Thalidomide. Synthesis 2001, 999–1000. [Google Scholar] [CrossRef]
  11. Peng, Y.; Song, G.; Qian, X. Imidation of cyclic carboxylic anhydrides under microwave irradiation. Synth. Commun. 2001, 31, 1927–1931. [Google Scholar]
  12. Kacprzak, K. Rapid and convenient microwave-assisted synthesis of aromatic imides and N-(hydroxymethyl)imides. Synth. Commun. 2003, 33, 1499–1507. [Google Scholar] [CrossRef]
  13. Bratulescu, G. Reaction of benzonitrile with dicarboxylic acids. Rev. Chim. (Bucharest) 2000, 51, 167–168. [Google Scholar]
  14. Nikpour, F.; Kazemi, S.; Sheikh, D. A facile and convenient synthesis of 1H-Isoindole-1,3(2H)-diones. Heterocycles 2006, 68, 1559–1564. [Google Scholar] [CrossRef]
  15. Hijji, Y. M.; Benjamin, E. Efficient microwave assisted syntheses of unsubstituted cyclic imides. Heterocycles 2006, 68, 2259–2267. [Google Scholar]
  16. Assem, Y.; Greiner, A.; Agarwal, S. Microwave-assisted controlled ring-closing cyclo-polymerization of diallyldimethylammonium chloride via the RAFT process. Macromol. Rapid Comm. 2007, 28, 1923–1928. [Google Scholar] [CrossRef]
  17. Lin, Y.-L.; Cheng, J.-Y.; Chu, Y.-H. Microwave-accelerated Claisen rearrangement in bicyclic imidazolium [β-3C-im][NTf2] ionic liquid. Tetrahedron 2007, 63, 10949–10957. [Google Scholar] [CrossRef]
  18. Khene, S.; Ogunsipe, A.; Antunes, E.; Nyokong, T. Microwave synthesis and photophysics of new tetrasulfonated tin(II) macrocycles. J. Porphyrins Phthalocyanines 2007, 11, 109–117. [Google Scholar] [CrossRef]
  19. Pal, S. K.; Kumar, S. Microwave-assisted synthesis of novel imidazolium-based ionic liquid crystalline dimers. Tetrahedron Lett. 2006, 47, 8993–8997. [Google Scholar] [CrossRef]
  20. Sugamoto, K.; Matsushita, Y.-I.; Kameda, Y.-H.; Suzuki, M.; Matsui, T. Microwave-assisted synthesis of N-hydroxyphthalimide derivatives. Synth. Commun. 2005, 35, 67–70. [Google Scholar] [CrossRef]
  21. Consonni, P.; Favara, D.; Omodei-Salé, A.; Bartolini, G.; Ricci, A. Reactivity of N-phenacyloxycarbamates and related systems in the presence of bases: study of a new [1,2] anionic rearrangement. J. Chem. Soc., Perkin Trans. 2 1983, 967–973. [Google Scholar]
  22. Kim, B. S.; Moon, S. S.; Hwang, B. K. Isolation, antifungal activity, and structure elucidation of the glutarimide antibiotic, streptimidone, produced by Micromonospora coerulea. J. Agric. Food Chem. 1999, 47, 3372–3380. [Google Scholar] [CrossRef] [PubMed]
  23. Butcher, R. J.; Hijji, Y. M.; Benjamin, E. cis-3-Aza­bicyclo­[3.2.0]heptane-2,4-dione. Acta Cryst. 2006, E62, o1266–o1268. [Google Scholar]
  24. CCDC 675565 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
  25. Wang, D.C.; Lin.; Jiang, L.; Sun, N. Perhydrophthalimide. Acta Cryst. 2007, E63, o3990–03990. [Google Scholar]
  • Sample Availability: Samples of the compounds are commerically available.

Supporting Data

Table 1. Crystal Data for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
Table 1. Crystal Data for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
Identification code3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione
Empirical formulaC8H11NO2
Formula weight153.18
Temperature203(2) K
Wavelength0.71073 Å
Crystal systemOrthorhombic
Space groupP21 21 21
Unit cell dimensionsa = 6.7185(4) Åα= 90°
b = 7.8339(4) Åβ= 90°
c = 14.2861(10) Åγ = 90°
Volume751.91(8) Å3
Z4
Density (calculated)1.353 Mg/m3
Absorption coefficient0.098 mm-1
F(000)328
Crystal size0.65 x 0.55 x 0.35 mm3
Theta range for data collection4.91 to 32.46°.
Index ranges-4<=h<=9, -9<=k<=11, -20<=l<=18
Reflections collected5210
Independent reflections2427 [R(int) = 0.0317]
Completeness to theta = 25.00°99.1 %
Absorption correctionSemi-empirical from equivalents
Max. and min. transmission1.00000 and 0.90324
Refinement methodFull-matrix least-squares on F2
Data / restraints / parameters2427 / 0 / 100
Goodness-of-fit on F20.873
Final R indices [I>2sigma(I)]R1 = 0.0393, wR2 = 0.0772
R indices (all data)R1 = 0.0674, wR2 = 0.0821
Absolute structure parameter-1.2(9)
Largest diff. peak and hole0.248 and -0.202 e.Å-3
Table 2. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103) for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
Table 2. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103) for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
AtomsxyzU(eq)
O(1)14804(1)4204(1)1252(1) 36(1)
O(2)9681(1)1315(1)2592(1)36(1)
N12075(1)3090(1)2005(1)28(1)
C(1)13916(1)2996(1)1573(1) 27(1)
C(2)14594(1)1165(1)1644(1)27(1)
C(3)15963(1)537(1)866(1)34(1)
C(4)14865(1)35(1)-21(1)34(1)
C(5)13199(1)-1214(1)201(1)33(1)
C(6)11673(1)-391(1)850(1)28(1)
C(7)12617(1)196(1)1778(1)27(1)
C(8)11271(1)1519(1)2197(1) 27(1)
Table 3. Bond lengths [Å] for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
Table 3. Bond lengths [Å] for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
BondsLengths
O(1)-C(1)1.2089(7)
O(2)-C(8)1.2185(9)
N-C(8)1.3718(8)
N-C(1)1.3840(9)
N-H(0A)0.8700
C(1)-C(2)1.5091(8)
C(2)-C(3)1.5241(10)
C(2)-C(7)1.5419(9)
C(2)-H(2A)0.9900
C(3)-C(4)1.5179(10)
C(3)-H(3A)0.9800
C(3)-H(3B)0.9800
C(4)-C(5)1.5208(10)
C(4)-H(4A)0.9800
C(4)-H(4B)0.9800
C(5)-C(6)1.5246(10)
C(5)-H(5A)0.9800
C(5)-H(5B)0.9800
C(6)-C(7)1.5401(10)
C(6)-H(6A)0.9800
C(6)-H(6B)0.9800
C(7)-C(8)1.5000(10)
C(7)-H(7A)0.9900
Table 4. Bond Angles [°] for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
Table 4. Bond Angles [°] for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
AtomsAngles
C(8)-N-C(1)113.19(5)
C(8)-N-H(0A)123.4
C(1)-N-H(0A)123.4
O(1)-C(1)-N124.68(6)
O(1)-C(1)-C(2)128.35(6)
N-C(1)-C(2)106.88(5)
C(1)-C(2)-C(3)116.13(5)
C(1)-C(2)-C(7)102.49(5)
C(3)-C(2)-C(7)116.87(5)
C(1)-C(2)-H(2A)106.9
C(3)-C(2)-H(2A)106.9
C(7)-C(2)-H(2A)106.9
C(4)-C(3)-C(2)113.50(6)
C(4)-C(3)-H(3A)108.9
C(2)-C(3)-H(3A)108.9
C(4)-C(3)-H(3B)108.9
C(2)-C(3)-H(3B)108.9
H(3A)-C(3)-H(3B)107.7
C(3)-C(4)-C(5)110.48(6)
C(3)-C(4)-H(4A)109.6
C(5)-C(4)-H(4A)109.6
C(3)-C(4)-H(4B)109.6
C(5)-C(4)-H(4B)109.6
H(4A)-C(4)-H(4B)108.1
C(4)-C(5)-C(6)110.47(6)
C(4)-C(5)-H(5A)109.6
C(6)-C(5)-H(5A)109.6
C(4)-C(5)-H(5B)109.6
C(6)-C(5)-H(5B)109.6
H(5A)-C(5)-H(5B)108.1
C(5)-C(6)-C(7)111.88(6)
C(5)-C(6)-H(6A)109.2
C(7)-C(6)-H(6A)109.2
C(5)-C(6)-H(6B)109.2
C(7)-C(6)-H(6B)109.2
H(6A)-C(6)-H(6B)107.9
C(8)-C(7)-C(6)107.52(6)
C(8)-C(7)-C(2)103.25(5)
C(6)-C(7)-C(2)113.23(6)
C(8)-C(7)-H(7A)110.8
C(6)-C(7)-H(7A)110.8
C(2)-C(7)-H(7A)110.8
O(2)-C(8)-N123.75(6)
O(2)-C(8)-C(7)128.51(6)
N-C(8)-C(7)107.61(6)
Symmetry transformations used to generate equivalent atoms:
Table 5. Anisotropic displacement parameters (Å2x 103) for eb1a. The anisotropic displacement factor exponent takes the form: -2π2 [ h2 a*2U11 + ... + 2 h k a* b* U12 ]
Table 5. Anisotropic displacement parameters (Å2x 103) for eb1a. The anisotropic displacement factor exponent takes the form: -2π2 [ h2 a*2U11 + ... + 2 h k a* b* U12 ]
U11U22U33U23U13U12
O(1)42(1)28(1)39(1)1(1)7(1)-8(1)
O(2)38(1) 28(1)42(1) -1(1)14(1)-4(1)
N32(1)20(1)33(1)-1(1)4(1)1(1)
C(1)31(1)26(1)23(1)0(1)-4(1)-5(1)
C(2)25(1)24(1)31(1)2(1)-5(1)-3(1)
C(3)25(1)29(1)47(1)0(1)5(1)4(1)
C(4)37(1)30(1)34(1)-2(1)9(1)1(1)
C(5)36(1)29(1)34(1)-6(1)2(1)2(1)
C(6)27(1)23(1)35(1)-6(1)-4(1)1(1)
C(7)29(1)23(1)28(1)4(1)1(1)0(1)
C(8)31(1)27(1)23(1)1(1)-1(1)-2(1)
Table 6. Hydrogen coordinates (x104) and isotropic displacement parameters (Å2x 103) for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
Table 6. Hydrogen coordinates (x104) and isotropic displacement parameters (Å2x 103) for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
atomxyzU(eq)
H(0A)114884048214134
H(2A)153441059223732
H(3A)16922143971640
H(3B)16715-452109440
H(4A)15798-491-46240
H(4B)143081057-31740
H(5A)13755-223350240
H(5B)12546-1569-38040
H(6A)10610-121398334
H(6B)1107559553534
H(7A)12791780221132
Table 7. Torsion angles [°] for for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
Table 7. Torsion angles [°] for for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione.
Torsional AtomsAtoms
C(8)-N-C(1)-O(1) 171.80(6)
C(8)-N-C(1)-C(2)-11.56(7)
O(1)-C(1)-C(2)-C(3)-32.24(10)
N-C(1)-C(2)-C(3) 151.28(6)
O(1)-C(1)-C(2)-C(7)-160.86(7)
N-C(1)-C(2)-C(7)22.66(7)
C(1)-C(2)-C(3)-C(4)-80.77(7)
C(7)-C(2)-C(3)-C(4)40.46(8)
C(2)-C(3)-C(4)-C(5)-52.03(7)
C(3)-C(4)-C(5)-C(6)61.99(7)
C(4)-C(5)-C(6)-C(7)-59.17(7)
C(5)-C(6)-C(7)-C(8)159.28(5)
C(5)-C(6)-C(7)-C(2)45.88(7)
C(1)-C(2)-C(7)-C(8)-24.88(6)
C(3)-C(2)-C(7)-C(8)-153.05(6)
C(1)-C(2)-C(7)-C(6)91.07(6)
C(3)-C(2)-C(7)-C(6)-37.09(8)
C(1)-N-C(8)-O(2)178.41(6)
C(1)-N-C(8)-C(7)-5.39(7)
C(6)-C(7)-C(8)-O(2)75.38(9)
C(2)-C(7)-C(8)-O(2)-164.68(7)
C(6)-C(7)-C(8)-N-100.59(6)
C(2)-C(7)-C(8)-N19.36(7)
Symmetry transformations used to generate equivalent atoms:
Table 8. Hydrogen bonds for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione [Å and °].
Table 8. Hydrogen bonds for 3a,4,5,6,7,7a-Hexahydro-1H-isoindole-1,3(2H)-dione [Å and °].
D-H...Ad(D-H)d(H...A)d(D...A) <(DHA)
N-H(0A)...O(2)#10.871.982.8472(7)175.8
Symmetry transformations used to generate equivalent atoms:
#1 -x+2,y+1/2,-z+1/2
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