Phosphorus-nitrogen compounds. 21. Syntheses, structural investigations, biological activities, and DNA interactions of new N/O spirocyclic phosphazene derivatives. the NMR behaviors of chiral phosphazenes with stereogenic centers upon the addition of chiral solvating agents

Article abstract of DOI:10.1021/ic100781v

The reactions of hexachlorocyclotriphosphazatriene, N₃P ₃Cl₆, with N/O-donor-type N-alkyl (or aryl)-o- hydroxybenzylamines (1a-1e) produce mono- (2a-2e), di- (3a-3d), and tri- (4a and 4b) spirocyclic phosphazenes. The tetrapyrrolidino monospirocyclic phosphazenes (2f-2i) are prepared from the reactions of partly substituted compounds (2a-2d) with excess pyrrolidine. The dispirodipyrrolidinophosphazenes (3e-3h) and trispirophosphazenes (3i-3k) are obtained from the reactions of trans-dispirophosphazenes with excess pyrrolidine and sodium (3-amino-1-propanoxide), respectively. Compounds 3a-3d have cis and trans geometric isomers. Only the trans isomers of these compounds are isolated. Compounds 3a-3h have two stereogenic P atoms. They are expected to be in cis (meso) and trans (racemic) geometric isomers. In the trans trispiro compounds (3i-3k), there are three stereogenic P atoms. They are expected to be in racemic mixtures. The stereogenic properties of 3a-3k are confirmed by ³¹P NMR spectroscopy upon the addition of the chiral solvating agent; (S)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol. The molecular structures of 3i-3k, 4a, and 4b look similar to a propeller, where the chemical environment of one P atom is different from that of others. Additionally, 4a and 4b are also expected to exist as cis-trans-trans and cis-cis-cis geometric isomers, but both of them are found to be in cis-trans-trans geometries. The solid-state structures of 2a, 2e, 2f, 3e, and 3f are determined by X-ray crystallography. The compounds 2f-2i, 3e-3i, and 3k are screened for antibacterial activity against Gram-positive and Gram-negative bacteria and for antifungal activity against yeast strains. These compounds (except 3f) have shown a strong affinity against most of the bacteria. Minimum inhibitory concentrations (MIC) are determined for 2f-2i, 3e-3i, and 3k. DNA binding and the nature of interaction with pUC18 plasmid DNA are studied. The compounds 2f-2i, 3e-3i, and 3k induce changes on the DNA mobility. The prevention of BamHI and HindIII digestion (except 2g) with compounds indicates that the compounds bind with nucleotides in DNA.

Full text of DOI:10.1021/ic100781v

Inorg. Chem. 2010, 49, 7057–7071 7057
DOI: 10.1021/ic100781v
Phosphorus-Nitrogen Compounds. 21. Syntheses, Structural Investigations,
Biological Activities, and DNA Interactions of New N/O Spirocyclic Phosphazene
Derivatives. The NMR Behaviors of Chiral Phosphazenes with Stereogenic Centers
upon the Addition of Chiral Solvating Agents
:
†
‡
‡
§
,‡
^
€
€
Muhammet Is-ıklan, Nuran Asmafiliz, Ezgi Elif Ozalp, Elif Ece Ilter, Zeynel Kılıc-,* Bunyemin C-os-ut,
^
^
||
z
0
#
#
€
€
€
€
Serkan Yes-ilot, Adem Kılıc-, Aslı Ozturk, Tuncer Hokelek, L. Yasemin Koc- Bilir, Leyla Ac-ık, and Emel Akyuz
†Department of Chemistry, Kırıkkale University, Kırıkkale, Turkey, ‡Department of Chemistry, Ankara
::
:
University, 06100 Ankara, Turkey, §TUBITAK, Scientific and Technical Research Council of Turkey, 06100
Ankara, Turkey, ^Department of Chemistry, Gebze Institute of Technology, 41400 Kocaeli, Turkey,
||Department of Physics, Pamukkale University, Denizli, Turkey, zDepartment of Physics, Hacettepe
University, 06800 Ankara, Turkey, 0Department of Biology, Ankara University, 06100 Ankara, Turkey, and
#Department of Biology, Gazi University, 06500 Ankara, Turkey
Received April 22, 2010
The reactions of hexachlorocyclotriphosphazatriene, N3P3Cl6, with N/O-donor-type N-alkyl (or aryl)-o-hydroxybenzy-
lamines (1a-1e) produce mono- (2a-2e), di- (3a-3d), and tri- (4a and 4b) spirocyclic phosphazenes. The
tetrapyrrolidino monospirocyclic phosphazenes (2f-2i) are prepared from the reactions of partly substituted
compounds (2a-2d) with excess pyrrolidine. The dispirodipyrrolidinophosphazenes (3e-3h) and trispirophospha-
zenes (3i-3k) are obtained from the reactions of trans-dispirophosphazenes with excess pyrrolidine and sodium (3-
amino-1-propanoxide), respectively. Compounds 3a-3d have cis and trans geometric isomers. Only the trans isomers
of these compounds are isolated. Compounds 3a-3h have two stereogenic P atoms. They are expected to be in cis
(meso) and trans (racemic) geometric isomers. In the trans trispiro compounds (3i-3k), there are three stereogenic P
atoms. They are expected to be in racemic mixtures. The stereogenic properties of 3a-3k are confirmed by 31P NMR
spectroscopy upon theaddition of thechiral solvating agent;(S)-(þ)-2,2,2-trifluoro-1-(90-anthryl)ethanol. Themolecular
structures of 3i-3k, 4a, and 4b look similar to a propeller, where the chemical environment of one P atom is different
from that of others. Additionally, 4a and 4b are also expected to exist as cis-trans-trans and cis-cis-cis geometric
isomers, but bothofthem are found tobe in cis-trans-trans geometries. The solid-statestructures of2a, 2e, 2f, 3e, and
3f are determined by X-ray crystallography. The compounds 2f-2i, 3e-3i, and 3k are screened for antibacterial activity
against Gram-positive and Gram-negative bacteria and for antifungal activity against yeast strains. These compounds
(except 3f) have shown a strong affinity against most of the bacteria. Minimum inhibitory concentrations (MIC) are
determined for 2f-2i, 3e-3i, and 3k. DNA binding and the nature of interaction with pUC18 plasmid DNA are studied.
The compounds 2f-2i, 3e-3i, and 3k induce changes on the DNA mobility. The prevention of BamHI and HindIII
digestion (except 2g) with compounds indicates that the compounds bind with nucleotides in DNA.
Introduction
chiral cyclophosphazenes in particular.1 Reactions of bifunc-
tional reagents with N3P3Cl6 may lead to spiro, ansa, bino,
dispiro, spiro-ansa, and trispirocyclophosphazenic derivatives.2
Both functional groups of the ligand may be replaced with
In recent years, there has been a considerable amount of
interest in the synthesis of spirocyclic phosphazenes in gen-
eral and in the determination of the strereogenic properties of
(2) (a) Porwolik-Czomperlic, I.; Brandt, K.; Clayton, T. A.; Davies, D. B.;
Eaton, R. J.; Shaw, R. A. Inorg. Chem. 2002, 41, 4944–4951. (b) Allcock,
H. R.; Sunderland, N. J.; Primrose, A. P.; Rheingold, A. L.; Guzei, I. A.; Parvez,
M. Chem. Mater. 1999, 11, 2478–2485. (c) Carriedo, G. A.; Martinez, J. I. F.;
Alonso, F. J. G.; Gonzalez, E. R.; Soto, A. P. Eur. J. Inorg. Chem. 2002,
1502–1510. (d) Chandrasekhar, V.; Athimoolam, A.; Srivatsan, S. G.; Sundaram,
P. S.; Verma, S.; Steiner, A.; Zacchini, S.; Butcher, R. Inorg. Chem. 2002, 41,
*To whom correspondence should be addressed. E-mail: zkilic@
science.ankara.edu.tr.
(1) (a) Chandrasekhar, V.; Krishnan, V. Adv. Inorg. Chem. 2002, 53,
159–211. (b) Bes-li, S.; Coles, S. J.; Davies, D. B.; Eaton, R. J.; Hursthouse, M. B.;
Kılıc-, A.; Shaw, R. A.; C-iftc-i, G. Y.; Yes-ilot, S-. J. Am. Chem. Soc. 2003, 125,
4943–4950. (c) Chandrasekhar, V.; Thilagar, P.; Pandian, B. M. Coord. Chem.
Rev. 2007, 251, 1045–1074. (d) Coles, S. J.; Davies, D. B.; Eaton, R. J.;
Hursthouse, M. B.; Kılıc-, A.; Shaw, R. A.; Uslu, A. Eur. J. Org. Chem. 2004,
1881–1886.
€
5162–5173. (e) Bilge, S.; Demiriz, S-.; Okumus-, A.; Kılıc-, Z.; Tercan, B.; Hokelek,
€
T.; B€uy€ukg€ungor, O. Inorg. Chem. 2006, 45, 8755–8767.
r
2010 American Chemical Society
Published on Web 06/28/2010
pubs.acs.org/IC

7058 Inorganic Chemistry, Vol. 49, No. 15, 2010
Is-ıklan et al.
two Cl atoms in a cis nongeminal route to give ansa
derivatives and in a geminal route to give spiro derivatives.
In addition, only one of the two functional groups may react
with N3P3Cl6 to give open-chain (dangling) compounds, and
the bifunctional reagents may replace two Cl atoms on two
different phosphazene rings to form bridged (bino) phospha-
zene derivatives. On the other hand, intermolecular conden-
sation reactions produce oligomers and cyclolinear or
cyclomatrix polymers. In the formation of these phosphazene
derivatives, many factors play an important role, e.g., solvent
polarities, temperature, size of the phosphazene ring, and
properties of the bifunctional ligands.1a,3 The stereogenic
properties of cyclophosphazenes have highly attracted inter-
est during the past decade.4 31P NMR spectroscopy upon the
addition of a chiral solvating agent (CSA)4b,5 and high-
performance liquid chromatography (HPLC) tecniques6
have been very useful in the investigation of the stereogenic
properties of phosphazenes.
Recently, our group published the paper5c about the
antibacterial and antifungal activity of tetrapyrrolidinofer-
rocenylphosphazenes. So, pyrrolidino-substituted N/O spir-
ocyclic phosphazenes are chosen in this study. As a particular
interest in our ongoing studies about N/O spirocyclic phos-
phazene derivatives,14 we report here in detail (i) the pre-
paration of new mono- (2a, 2b, and 2e), di- (3a and 3b), and
trispirocyclic (4a and 4b) phosphazenes, (ii) the synthesis of
tetra- (2f-2i) and dipyrrolidinophosphazenes (3e-3h), (iii)
the preparation of trans-trispirocyclic derivatives (3i-3k)
(Scheme 1), (iv) the stereogenic properties of 3a-3k, which
are investigated by 31P NMR measurements in the presence
of a CSA, (v) the determination of the structures of com-
pounds by elemental analyses, mass spectrometry (MS),
Fourier transform infrared (FTIR), one-dimensional (1D)
1H, 13C, and 31P NMR, distortionless enhancement by polari-
zation transfer (DEPT), and two-dimensional (2D) hetero-
nuclear shift correlation (HETCOR), (vi) the solid-state
structures of 2a, 2e, 2f, 3e, and 3f established by X-ray
diffraction techniques, (vii) investigations of the antibacterial
and antifungal activity of 2f-2i, 3e-3i, and 3k, and (xi)
interactions between these compounds and pUC 18 plasmid
DNA examined by agarose gel electrophoresis.
Phosphazene derivatives are also of considerableinterest in
various areas such as advanced elastomers,7 rechargeable
batteries,8 anticancer,9 antibacterial reagents,10 and biome-
dical materials.11 The DNA binding abilities of phosphazenes
are well-known12 and can be examined by agarose gel
electrophoresis.13
Experimental Section
General Methods. Reagents were of commercial grade and
were used without further purification. Hexachlorocyclotripho-
sphazatriene was purchased from Aldrich. All experiments were
carried out under an argon atmosphere. All reactions were
monitored using thin-layer chromatography (TLC) in different
(3) Allcock, H. R.; Diefenbach, U.; Pucher, S. R. Inorg. Chem. 1994, 33,
3091–3095.
:
(4) (a) Ilter, E. E.; C-aylak, N.; Is-ıklan, M.; Asmafiliz, N.; Kılıc-, Z.;
:
€
Hokelek, T. J. Mol. Struct. 2004, 697, 119–129. (b) Asmafiliz, N.; Ilter, E. E.;
€
€
Is-ıklan, M.; Kılıc-, Z.; Tercan, B.; C-aylak, N.; Hokelek, T.; B€uy€ukgu€ngor, O. J.
Mol. Struct. 2007, 30, 172–183. (c) Bhuvan Kumar, N. N.; Kumara Swamy, K. C.
Chirality 2008, 20, 781–789.
solvents and chromatographed using silica gel. 1H, 13C, and 31
P
NMR spectra were recorded on a Bruker DPX FT-NMR
spectrometer (SiMe4 as an internal standard and 85% H3PO4
as an external standard), operating at 499.94, 125.72, and
202.38 MHz. The spectrometer was equipped with a 5 mm
PABBO BB inverse-gradient probe. Standard Bruker pulse
programs were used. IR spectra were recorded on a Mattson
1000 FTIR spectrometer in KBr disks and were reported in
reciprocal centimeter units. Microanalyses were carried out by
(5) (a) Bes-li, S.; Coles, S. J.; Davies, D. B.; Eaton, R. J.; Hursthouse,
M. B.; Kılıc-, A.; Shaw, R. A.; Uslu, A.; Yes-ilot, S-. Inorg. Chem. Commun.
2004, 7, 842–846. (b) Coles, S. J.; Davies, D. B.; Hursthouse, M. B.; Kılıc-, A.;
S-ahin, S-.; Shaw, R. A.; Uslu, A. J. Organomet. Chem. 2007, 692, 2811–2821.
€
€
€
(c) Asmafiliz, N.; Kılıc-, Z.; Ozt€urk, A.; Hokelek, T.; Koc-, L. Y.; Ac-ık, L.; Kısa, O.;
::
ꢀ
Albay, A.; Ust€undag, Z.; Solak, A. O. Inorg. Chem. 2009, 48, 10102–10116.
(6) (a) Bui, T. T.; Coles, S. J.; Davies, D. B.; Drake, A. F.; Eaton, R. J.;
Hursthouse, M. B.; Kılıc-, A.; Shaw, R. A.; Yes-ilot, S-. Chirality 2005, 17,
438–443. (b) Bes-li, S.; Davies, D. B.; Kılıc-, A.; Shaw, R. A.; S-ahin, S-.; Uslu, A.;
Yes-ilot, S-. J. Chromatogr. A 2006, 1132, 201–205. (c) Yes-ilot, S-.; C-os-ut, B.
Inorg. Chem. Commun. 2007, 10, 88–93. (d) Coles, S. J.; Davies, D. B.;
::
:
the microanalytical service of TUBITAK-Turkey. MS spectra
are recorded on a Bruker MicrOTOF LC-MS spectrometer
using an electrospray ionization (ESI) method; 35Cl values were
used for calculated masses. Mycobacterial susceptibility testing
was performed by the BACTEC MGIT 960 (Becton Dickinson,
Sparks, MD) system (section S1 in the Supporting Information).
The DNA binding abilities were examined using agarose gel
electrophoresis (section S2 in the Supporting Information).
Preparation of Compounds. N-Benzyl- (1a),15 N-isopropyl- (1b),16
N-propyl- (1c),17 N-ethyl- (1d),17 and N-methyl-o-hydroxybenz-
ylamine (1e)15 were synthesized according to the methods repor-
ted in the literature. Also, compounds 2c, 2d, 3c, and 3d were
obtained from the reaction of 1c and 1d with N3P3Cl6 according
to the reported procedure.14a The numbering of H and C atoms
in phosphazene derivatives is given in Scheme 1.
Hurtshouse, M. B.; Kılıc-, A.; C-os-ut, B.; Yes-ilot, S-. Acta Crystallogr., Sect. B
:
ꢀ
2009, 65, 355–362. (e) C-os-ut, B.; Ibis-oglu, H.; Kılıc-, A.; Yes-ilot, S-. Inorg. Chim.
Acta 2009, 362, 4931–4936.
(7) (a) Allcock, H. R.; Napierala, M. E.; Cameron, C. G.; O’Connor,
S. J. M. Macromolecules 1996, 29, 1951–1956. (b) Allcock, H. R. Curr. Opin.
Solid State Mater. Sci. 2006, 10, 231–240.
(8) (a) Xu, G.; Lu, Q.; Yu, B.; Wen, L. Solid State Ionics 2006, 177,
305–309. (b) Morford, R. V.; Kellam, E. C.; Hofmann, M. A.; Baldwin, R.;
Allcock, H. R. Solid State Ionics 2000, 133, 171–177. (c) Allcock, H. R.; Kellam,
E. C.; Morford, R. V.; Conner, D. A.; Welna, D. T.; Chang, Y.; Allcock, H. R.
Macromolecules 2007, 40, 322–328. (d) Klein, R.; Welna, D. T.; Weikel, A.;
Allcock, H. R.; Runt, J. Macromolecules 2007, 40, 3990–3995.
(9) (a) Porwolik-Czomperlik, I.; Siwy, M.; S-ek, D.; Kaczmarczyk, B.;
Nasulewicz, A.; Jaroszewicz, I.; Pelczynska, M.; Opolski, A. Acta Polym.
Pharm. 2004, 66, 267–272. (b) Siwy, M.; S-ek, D.; Kaczmarczyk, B.; Jaroszewicz,
I.; Nasulewicz, A.; Pelczynska, M.; Nevozhay, D.; Opolski, A. J. Med. Chem.
4,4,6,6-Tetrachloro-3-benzyl-3,4-dihydrospiro[1.3.2]benzoxa-
zaphosphorine[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (2a).
A solution of 1a (2.00 g, 9.38 mmol) in tetrahydrofuran (THF;
50 mL) and triethylamine (2.17 mL) was slowly added to a
stirred solution of N3P3Cl6 (3.26 g, 9.38 mmol) in THF (100 mL)
2006, 49, 806–810.
:
€
€
€
ꢀ
(10) (a) Yılmaz, O.; Aslan, F.; Ozturk, A. I.; Vanlı, N. S.; Kırbag, S.;
€
Arslan, M. Bioorg. Chem. 2002, 30, 303–314. (b) Konar, V.; Yılmaz, O.; Aslan,
:
€
ꢀ
F.; Ozt€urk, A. I.; Kırbag, S.; Arslan, M. Bioorg. Chem. 2000, 28, 214–225.
(11) (a) Greish, Y. E.; Bender, J. D.; Lakshmi, S.; Brown, P. W.; Allcock,
H. R.; Laurencin, C. T. Biomaterials 2005, 26, 1–9. (b) Nair, L.; Bhattacharyya,
S.; Bender, J. D.; Greish, Y E.; Brown, P. W.; Allcock, H.; Laurencin, C. T.
Biomacromolecules 2004, 5, 2212–2220.
:
€
(14) (a) Ilter, E. E.;Asmafiliz, N.; Kılıc-, Z.; Is-ıklan, M.;Hokelek, T.; C-aylak,
€
N.; S-ahin, E. Inorg. Chem. 2007, 46, 9931–9944. (b) Is-ıklan, M; Sonkaya, O.;
(12) (a) Grochowski, J.; Serda, P.; Brandt, K. Drug Res. (Arzneim.
Forsch.) 1994, 44, 655–658. (b) Brandt, K.; Bartczak, T. J.; Kruszynski, R.;
Porwolik-Czomperlik, I. Inorg. Chim. Acta 2001, 322, 138–144.
(13) Turner, P. C.; McLennan, A. G.; Bates, A. D.; White, M. R. H.
Molecular Biology, 2nd ed.; Springer: Berlin, 2000.
€
C-os-ut, B.; Yes-ilot, S-.; Hokelek, T. Polyhedron 2010, 29, 1612–1618.
(15) Andreu, R.; Ronda, J. C. Synth. Commun. 2008, 38, 2316–2329.
(16) Robertson, A.; Jones, D. G. Patent 681993, 1952.
(17) (a) Cromwell, N. H.; Hoeksema, H. J. Am. Chem. Soc. 1945, 67,
1658–1660. (b) Bar-Haim, G.; Kol, M. Org. Lett. 2004, 6(20), 3549–3551.

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 7059
Scheme 1. Reaction Pathway of N3P3Cl6 with N-Alkyl (or Aryl)-o-hydroxybenzylamines (1a-1e)
at room temperature. The mixture was stirred for 8 h, and the
precipitated triethylamine hydrochloride was filtered off. The
solvent was evaporated completely, and the oily residue was
purified by column chromatography with toluene. The product
was crystallized from n-hexane (ethyl acetate, Rf = 0.85). Yield:
4.00 g (87%). Mp: 96 ꢀC. Anal. Calcd for C14H13N4OP3Cl4: C,
34.46; H, 2.68; N, 11.48. Found: C, 34.57; H, 2.81; N, 11.42. ESI-
MS (fragments were based on 35Cl): m/z 487 [M þ H]þ. FTIR
(KBr, cm-1): ν 3060, 3033 (C-H aromatic), 2916, 2862 (C-H
aliphatic), 1248, 1179 (PdN), 572, 514 (P-Cl). 1H NMR(CDCl3,
ppm): δ 4.15 (d, 2H, 3JPH = 15.2 Hz, H1), 4.25 (d, 2H, 3JPH = 9.7
Hz, NCH2), 6.95-7.43 (9H, Ar-H). 13C NMR (CDCl3, ppm): δ
51.00 (d, 2JPC = 4.2 Hz, NCH2), 47.48 (C1), 118.75 (d, 3JPC = 8.4
Hz, C4), 123.49 (d, 3JPC = 7.5 Hz, C2), 128.07 (C7), 124.40 (C6),
126.73, 128.35, 128.85 (Ar-C), 135.75 (d, 3JPC = 6.8 Hz, Ar-C),
129.07 (C5), 149.88 (d, 2JPC = 8.2 Hz, C3).
4,4,6,6-Tetrachloro-3-isopropyl-3,4-dihydrospiro[1.3.2]benzo-
xazaphosphorine[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (2b).
The workup procedure was similar to that of compound 2a, using
1b (1.42 g, 8.61 mmol), N3P3Cl6 (2.99 g, 8.61 mmol), and triethy-
lamine (2.42 mL) (ethyl acetate, Rf = 0.87). Yield: 3.20 g (84%).
Mp: 106 ꢀC. Anal. Calcd for C10H13N4OP3Cl4:C,27.27;H,2.95;N,
12.73. Found: C, 27.73; H, 2.72; N, 12.68. ESI-MS (fragments were
based on 35Cl): m/z 441 [M þ H]þ. FTIR (KBr, cm-1):ν 3072, 3034
(C-H aromatic), 2921, 2862 (C-H aliphatic), 1218, 1180 (PdN),
573, 515 (P-Cl). 1H NMR (CDCl3, ppm): δ 1.28 [d, 6H, 3JHH
=
6.5 Hz, CH(CH3)2], 3.81 (m, 1H, 3JHH = 6.5 Hz, 3JPH = 12.0 Hz,
NCH), 4.21 (d, 2H, 3JPH = 16.5 Hz, H1), 7.09-7.28 (4H, Ar-H).
13C NMR (CDCl3, ppm): δ 20.19 [d, 2JPC = 4.0, CH(CH3)2], 41.22
(d, 2JPC = 2.5 Hz, C1), 47.23 [d, 2JPC = 5.0 Hz, CH(CH3)2], 118.88
(d, 3JPC = 7.8 Hz, C4), 124.57 (C6), 125.18 (d, 3JPC = 7.0 Hz, C2),
126.65 (C5), 129.20 (C7), 150.31 (d, 2JPC = 8.3 Hz, C3).

7060 Inorganic Chemistry, Vol. 49, No. 15, 2010
Is-ıklan et al.
4,4,6,6-Tetrachloro-3-methyl-3,4-dihydrospiro[1.3.2]benzoxa-
zaphosphorine[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (2e).
The workup procedure was similar to that of compound 2a,
using 1e (1.39 g, 10.15 mmol), N3P3Cl6 (3.53 g, 10.17 mmol), and
triethylamine (2.85 mL). The oily residue was purified by column
chromatography with benzene, and the product was crystallized
from n-hexane (ethyl acetate, Rf = 0.86). Yield: 3.25 g (78%).
Mp: 101 ꢀC. Anal. Calcd for C8H9N4OP3Cl4: C, 23.30; H, 2.18;
N, 13.59. Found: C, 23.62; H, 2.15; N, 13.56. ESI-MS (fragments
were based on 35Cl): m/z 412 [M]þ. FTIR (KBr, cm-1): ν 3071,
3046 (C-H aromatic), 2959, 2859 (C-H aliphatic), 1261, 1163
(PdN), 577, 506 (P-Cl). 1H NMR (CDCl3, ppm): δ 2.80 (d, 3H,
using 2c (1.04 g, 2.36 mmol) and pyrrolidine (2.33 mL, 28.32
mmol). After excess triethylamine (1.66 mL) was added to the
solution, the mixture was refluxed for another 4 h. The solvent
was evaporated, and the crude product was purified by column
chromatography with n-hexane-ethyl acetate (2:4) and crystal-
lized from n-hexane (ethyl acetate, Rf = 0.63). Yield: 1.07 g
(78%). Mp: 119 ꢀC. Anal. Calcd for C26H45N8OP3: C, 53.97; H,
7.84; N, 19.37. Found: C, 53.87; H, 19.27; N, 7.71. ESI-MS
(fragments were based on 35Cl): m/z 579 [M]þ. FTIR (KBr, cm-1):
ν 3057, 3039 (C-H aromatic), 2962, 2868 (C-H aliphatic),
1234, 1188 (PdN). 1H NMR (CDCl3, ppm): δ 0.87 (t, 3H,
3JHH = 7.5 Hz, NCH2CH2CH3), 1.63 (m, 2H, 3JHH = 7.5 Hz,
3
3
3JPH = 13.7 Hz, NCH3), 4.28 (d, 2H, JPH = 15.9 Hz, H1),
NCH2CH2), 1.72, 1.76 [m, 16H, JHH = 6.3 Hz, NCH2CH2
7.05-7.35 (4H, Ar-H). 13C NMR (CDCl3, ppm): δ 34.60 (d,
(pyrr)], 2.99 (m, 2H, 3JHH = 7.5 Hz, NCH2), 3.08, 3.11 [m, 16H,
3JHH = 6.3 Hz, NCH2 (pyrr)], 4.21 (d, 2H, 3JPH = 14.5 Hz, H1),
6.82-7.09 (4H, Ar-H). 13C NMR (CDCl3, ppm): δ 11.79
3
2JPC = 2.7 Hz, NCH3), 51.20 (C1), 118.80 (d, JPC = 8.7 Hz,
C4), 122.80 (d, JPC = 7.3 Hz, C2), 124.20 (C6), 126.60 (C5),
3
128.90 (C7), 149.80 (d, 2JPC = 7.9 Hz, C3).
(NCH2CH2CH3), 21.63 (d, JPC = 5.0 Hz NCH2CH2), 26.57
3
[dd, 3JPC = 9.2 Hz, NCH2CH2 (pyrr)], 26.63 [dd, 3JPC = 9.3 Hz,
NCH2CH2 (pyrr)], 46.37, 46.25 [NCH2 (pyrr)], 49.03 (C1), 50.21
(d, 2JPC = 2.3 Hz, NCH2), 118.66 (d, 3JPC = 7.5 Hz, C4), 122.17
4,4,6,6-Pyrrolidino-3-benzyl-3,4-dihydrospiro[1.3.2]benzoxa-
zaphosphorine[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (2f).
A solution of compound 2a (1.20 g, 2.46 mmol) in dry THF
(150 mL) was added slowly to a solution of pyrrolidine (2.42 mL,
29.53 mmol), and the resulting solution was then stirred and
refluxed for 22 h. After excess triethylamine (1.72 mL) was
added to the solution, the mixture was refluxed for another 3 h.
The solvent was evaporated, and the oily product was purified
by column chromatography using n-hexane-ethyl acetate (1:3)
as an eluent. The product was crystallized from n-hexane (ethyl
acetate, Rf = 0.69). Yield: 1.08 g (70%). Mp: 128 ꢀC. Anal. Calcd
for C30H45N8OP3: C, 57.50; H, 7.24; N, 17.88. Found: C, 57.16;
H, 6.96; N, 17.77. ESI-MS (fragments were based on 35Cl): m/z
627 [M þ H]þ. FTIR (KBr, cm-1): ν 3060, 3033 (C-H aromatic),
2916, 2862 (C-H aliphatic), 1248, 1179 (PdN). 1HNMR(CDCl3,
ppm): δ 1.83, 1.75 [m, 16H, NCH2CH2 (pyrr)], 3.21, 3.12 [d,
16H, 3JPH = 10.0 Hz, NCH2 (pyrr)], 4.11 (d, 2H, 3JPH = 15.0
Hz, H1), 4.26 (d, 2H, 3JPH = 10.0 Hz, NCH2), 6.90-7.48 (9H,
Ar-H). 13C NMR (CDCl3, ppm): δ 26.60, 26.63 [3JPC = 8.8 Hz,
NCH2CH2 (pyrr)], 46.43, 46.46 [2JPC = 2.5 Hz, NCH2 (pyrr)],
3
(C6), 124.83 (d, JPC = 7.5 Hz, C2), 126.72 (C5), 127.89 (C7),
152.18 (d, 2JPC = 7.9 Hz, C3).
4,4,6,6-Pyrrolidino-3-ethyl-3,4-dihydrospiro[1.3.2]benzoxaza-
phosphorine[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (2i).
The workup procedure was similar to that of compound 2f,
using 2d (1.44 g, 3.39 mmol) and pyrrolidine (3.33 mL, 40.56
mmol). After excess triethylamine (2.35 mL) was added to the
solution, the mixture was refluxed for another 3 h. The solvent
was evaporated, and the oily product was purified by column
chromatography using n-hexane-ethyl acetate (1:4) as an elu-
ent. The product was crystallized from n-hexane (ethyl acetate,
Rf = 0.49). Yield: 1.52 g (79%). Mp: 106 ꢀC. Anal. Calcd for
C25H43N8OP3: C, 53.18; H, 7.68; N, 19.85. Found: C, 53.35; H,
7.58; N, 19.76. ESI-MS (fragments were based on 35Cl): m/z 565
[M]þ. FTIR (KBr, cm-1): ν 3064, 3045 (C-H aromatic), 2961,
1
2865 (C-H aliphatic), 1240, 1197 (PdN). H NMR (CDCl3,
3
ppm): 1.19 (t, 3H, JHH = 7.0 Hz, NCH2CH3), 1.74, 1.77 [m,
=
51.73 (d, 2JPC = 2.5 Hz, NCH2), 48.42 (C1), 118.83 (d, 3JPC
=
16H, 3JHH = 6.3 Hz, NCH2CH2 (pyrr)], 3.14 (m, 2H, 3JHH
7.0 Hz, NCH2), 3.13, 3.17 [m, 16H, JHH = 6.3 Hz, NCH2
7.5 Hz, C4), 124.42 (d, 3JPC = 7.5 Hz, C2), 122.35 (C6), 127.25
(C5), 128.05 (C7), 126.95, 128.51, 128.82 (Ar-C) 138.85 (d,
3JPC = 8.8 Hz, Ar-C), 151.28 (d, 2JPC = 7.5 Hz, C3).
3
3
(pyrr)], 4.22 (d, 2H, JPH = 14.5 Hz, H1), 6.83-7.00 (4H,
3
Ar-H). 13C NMR (CDCl3, ppm): δ 13.66 (d, JPC = 5.2 Hz,
NCH2CH3), 26.64 [d, 3JPC = 7.8 Hz, NCH2CH2 (pyrr)], 26.58
[d, 3JPC = 8.0 Hz, NCH2CH2 (pyrr)], 42.63 (d, 2JPC = 2.5 Hz,
C1), 48.32 (NCH2), 46.27, 46.38 [NCH2 (pyrr)], 118.65 (d, 3JPC
= 7.5 Hz, C4), 122.23 (C6), 124.83 (d, 3JPC = 7.5 Hz, C2), 126.77
(C5), 127.90 (C7), 152.10 (d, 2JPC = 8.0 Hz, C3).
4,4,6,6-Pyrrolidino-3-isopropyl-3,4-dihydrospiro[1.3.2]benzo-
xazaphosphorine[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (2g).
The workup procedure was similar to that of compound 2f,
using 2b (1.50 g, 3.54 mmol) and pyrrolidine (3.49 mL, 42.48
mmol). After excess triethylamine (2.46 mL) was added to the
solution, the mixture was refluxed for another 4 h. The solvent
was evaporated, and the crude product was purified by column
chromatography with toluene-THF (3:1). The product was
crystallized from acetonitrile (ethyl acetate, Rf = 0.55). Yield:
1.40 g (68%). Mp: 133 ꢀC. Anal. Calcd for C26H45N8OP3: C,
53.98; H, 7.79; N, 19.38. Found: C, 54,75; H, 7.94; N, 18.91. ESI-
MS (fragments were based on 35Cl): m/z 579 [M þ H] þ. FTIR
(KBr, cm-1): ν 3078, 3044 (C-H aromatic), 2963, 2864 (C-H
aliphatic), 1218, 1180 (PdN). 1H NMR (CDCl3, ppm): δ 1.12 [d,
3H, 3JHH = 7.0 Hz, NCH(CH3)2], 1.18 [d, 3H, 3JHH = 7.0 Hz,
6,6-Dichloro-trans-bis{3-benzyl-3,4-dihydrospiro[1.3.2]benzo-
xazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (3a).
A solution of compound 1a (2.00 g, 9.38 mmol) in THF (100
mL) and triethylamine (5.27 mL) was slowly added to a stirred
solution of N3P3Cl6 (1.63 g, 4.69 mmol) in boiling THF (50 mL).
The mixture was refluxed for 12 h, and the precipitated triethy-
lamine hydrochloride was filtered off. The solvent was evapo-
rated completely, and the oily residue was purified by column
chromatography with benzene. The trans product was crystal-
lized from n-heptane (ethyl acetate, Rf = 0.78). Yield: 1.98 g
(67%). Mp: 113 ꢀC. Anal. Calcd for C28H26N5O2P3Cl2: C,
53.55; H, 4.17; N, 11.15. Found: C, 53.67; H, 4.21; N, 11.42.
ESI-MS (fragments were based on 35Cl): m/z 628 [M þ H]þ.
FTIR (KBr, cm-1): ν 3060, 3031 (C-H aromatic), 2939, 2844
(C-H aliphatic), 1256, 1179 (PdN), 588, 510 (P-Cl). 1H NMR
(CDCl3, ppm): δ 4.08-4.41 (4H, NCH2), 4.08-4.41 (m, 4H,
H1), 6.95-7.50 (18H, Ar-H). 13C NMR (CDCl3, ppm): δ 47.89
(C1), 51.44 (d, 2JPC = 2.5 Hz, NCH2), 118.97 (C4), 123.99 (C2),
126.93 (C5 and C6), 127.97 (C7), 128.91, 128.82, 136.91 (Ar-C),
150.58 (C3).
3
NCH(CH3)2], 1.76, 1.72 [m, 16H, JHH = 6.6 Hz, NCH2CH2
(pyrr)], 3.08, 3.12 [m, 16H, 3JHH = 6.6 Hz, NCH2 (pyrr)], 3.92
3
3
(m, 1H, JHH = 7.0 Hz, NCH), 4.10 (d, 2H, JPH = 16.3 Hz,
H1), 6.83-7.09 (4H, Ar-H). 13C NMR (CDCl3, ppm): δ 20.46
[d, JPC = 4.3 Hz, CH(CH3)2], 26.51, 26.57 [3JPC = 7.3 Hz,
3
NCH2CH2 (pyrr)], 41.31 (d, 2JPC2 = 6.7 Hz, C1), 46.35 [d, 2JPC
=
7.5 Hz, CH(CH3)2], 46.26 [d, JPC = 5.8 Hz, NCH2 (pyrr)],
46.22 [d, 2JPC = 5.7 Hz, NCH2 (pyrr)], 118.61 (C4), 122.26 (d,
3JPC = 9.8 Hz, C2) 127.81 (C5), 126.46 (C6), 127.89 (C7), 152.15
(d, 2JPC = 8.2 Hz, C3).
4,4,6,6-Pyrrolidino-3-propyl-3,4-dihydrospiro[1.3.2]benzoxa-
zaphosphorine[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (2h).
The workup procedure was similar to that of compound 2f,
6,6-Dichloro-trans-bis{3-isopropyl-3,4-dihydrospiro[1.3.2]-
benzoxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosph-
orine (3b). The workup procedure was similar to that of compound

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 7061
3a, using1b (1.92 g, 11.64 mmol), N3P3Cl6 (2.02 g, 5.82 mmol), and
triethylamine (2.50 mL). The oily residue was purified by column
chromatography with toluene. The trans product was crystallized
from n-hexane (ethyl acetate, Rf = 0.37). Yield: 2.40 g (77%). Mp:
117 ꢀC. Anal. Calcd for C20H26N5O2P3Cl2: C, 45.11; H, 4.89; N,
13.16. Found: C, 45.35; H, 4.98; N, 13.08. ESI-MS (fragments were
based on 35Cl): m/z 532 [M]þ. FTIR (KBr, cm-1): ν 3064, 3048
(C-H aromatic), 2933, 2842 (C-H aliphatic), 1218, 1180 (PdN),
solvent was evaporated, and the product was purified by column
chromatography using n-hexane-ethyl acetate (7:4) as an eluent
(ethyl acetate, Rf = 0.28). Yield: 1.58 g (57%). Mp: 112 ꢀC.
Anal. Calcd for C28H42N7O2P3: C, 55.90; H, 7.04; N, 16.29.
Found: C, 56.19; H, 7.01; N, 16.13. ESI-MS (fragments were based
on 35Cl): m/z 602 [M]þ. FTIR (KBr, cm-1): ν 3082, 3046 (C-H
1
aromatic), 2959, 2870 (C-H aliphatic), 1224, 1167 (PdN). H
NMR (CDCl3, ppm): δ 0.95 (t, 6H, 3JHH = 7.4 Hz, NCH2CH2-
CH3), 1.70 (m, 4H, 3JHH = 7.4 Hz, NCH2CH2), 1.82, 1.85 [m,
8H, NCH2CH2 (pyrr)], 3.09 (m, 4H, JPH = 13.1 Hz, NCH2),
598, 510 (P-Cl). 1H NMR (CDCl3, ppm): δ 1.30 (d, 6H, 3JHH
=
3
6.5 Hz, NCHCH3), 1.35 (d, 6H, 3JHH = 6.5 Hz, NCHCH3), 4.00
(m, 1H, 3JHH = 6.5 Hz, 3JPH = 12.3 Hz, NCHCH3), 4.29 (m, 1H,
2
3.15, 3.26 [m, 8H, NCH2 (pyrr)], 4.22 (2H, JHH = 13.8 Hz,
3JPH = 7.1 Hz, H1), 4.26 (2H, 2JHH = 14.6 Hz, 3JPH = 7.7 Hz,
H1), 6.90-7.17 (8H, Ar-H). 13C NMR (CDCl3, ppm): δ 11.62
3JHH = 6.5 Hz, 3JPH = 13.5 Hz, NCHCH3), 4.15 (4H, 2JHH
=
14.5 Hz, 3JPH = 10.0 Hz, H1), 7.04-7.31 (8H, Ar-H). 13C NMR
(CDCl3, ppm): δ 20.18, 20.17 (NCHCH3), 41.30 (C1), 46.86
(NCHCH3), 118.70 (t, 3JPC = 7.7 Hz, C4), 125.65 (d, 3JPC = 3.4
Hz, C2), 123.88 (C6), 126.66 (C5), 128.72 (C7), 150.87 (d, 2JPC =3.9
Hz, C3).
3
(NCH2CH2CH3), 21.25 (d, JPC = 2.1 Hz, NCH2CH2), 26.40
[d, 3JPC = 9.2 Hz, NCH2CH2 (pyrr)], 46.00 [d, 2JPC = 4.1 Hz,
NCH2 (pyrr)], 48.72 (NCH2), 50.01 (C1), 118.44 (dd, 3JPC = 7.8
Hz, C4), 122.38 (C6), 124.64 (dd, 3JPC = 7.6 Hz, C2), 126.51 (C5),
127.88 (C7), 151.56 (dd, 2JPC = 7.7 Hz, C3).
6,6-Pyrrolidino-trans-bis{3-benzyl-3,4-dihydrospiro[1.3.2]-
benzoxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphos-
phorine (3e). To a THF (75mL) solution of 3a (1.00g, 1.59 mmol)
was added 1.00 mL of pyrrolidine (12.70 mmol) in THF (75 mL),
and the mixture was refluxed for 25 h. After excess triethylamine
(0.89 mL) was added to the solution, the mixture was refluxed
for another 4 h. The solvent was evaporated, and the crude
product was purified by column chromatography with toluene-
THF (7:1). The product was crystallized from n-hexane (ethyl
acetate, Rf = 0.45). Yield: 0.60 g (54%). Mp: 142 ꢀC. Anal.
Calcd for C36H42N7O2P3: C, 61.97; H, 6.07; N, 14.05. Found: C,
61.88; H, 6.02; N, 13.79. ESI-MS (fragments were based on
35Cl): m/z 698 [M]þ. FTIR (KBr, cm-1): ν 3062, 3028 (C-H
6,6-Pyrrolidino-trans-bis{3-ethyl-3,4-dihydrospiro[1.3.2]benz-
oxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine
(3h). The workup procedure was similar to that of compound 3g,
using 3d (0.60 g, 1.69 mmol) and pyrrolidine (0.78 mL, 9.51
mmol). After excess triethylamine (0.49 mL) was added to the
solution, the mixture was refluxed for another 3 h (ethyl acetate,
Rf = 0.69). Yield: 1.53 g (55%). Mp: 134 ꢀC. Anal. Calcd for
C26H38N7O2P3: C, 54.44; H, 6.67; N, 17.09. Found: C, 54.28; H,
6.34; N, 16.90. ESI-MS (fragments were based on 35Cl): m/z 574
[M]þ. FTIR (KBr, cm-1): ν 3071, 3045 (C-H aromatic), 2968,
1
2869 (C-H aliphatic), 1237, 1170 (PdN). H NMR (CDCl3,
ppm): δ 1.27 (t, 6H, 3JHH = 6.9 Hz, NCH2CH3), 1.80, 1.84 [m,
8H, NCH2CH2 (pyrr)], 3.18 (m, 4H, JHH = 6.9 Hz, NCH2),
1
3
aromatic), 2959, 2864 (C-H aliphatic), 1215, 1172 (PdN). H
2
NMR (CDCl3, ppm): δ 1.72, 1.79 [m, 8H, NCH2CH2 (pyrr)],
3.21, 3.25 [m, 8H, NCH2 (pyrr)], 4.21 (2H, JHH = 14.7 Hz,
3.18 [m, 4H, 3JPH = 9.3 Hz, NCH2 (pyrr)], 3.30 [m, 4H, 3JPH
=
3JPH = 7.8 Hz, H1), 4.24 (2H, 2JHH = 14.5 Hz, 3JPH = 8.1 Hz,
H1), 6.90-7.17 (8H, Ar-H). 13C NMR (CDCl3, ppm): δ 13.24
(NCH2CH3), 26.37 [d, 3JPC = 9.1 Hz, NCH2CH2 (pyrr)], 42.51
9.2 Hz, NCH2 (pyrr)], 4.13 (2H, 2JHH = 14.8 Hz, 3JPH = 7.6 Hz,
H1), 4.16 (2H, 2JHH = 14.8 Hz, 3JPH = 6.7 Hz, H1), 4.39 (4H,
3JPH = 9.8 Hz, NCH2), 7.15-7.55 (18H, Ar-H). 13C NMR
2
(NCH2), 46.01 [d, JPC = 3.8 Hz, NCH2 (pyrr)], 48.03 (C1),
118.43 (C4), 122.37 (C5), 124.52 (dd, 3JPC = 7.1 Hz, C2), 126.52
(C6), 127.81 (C7), 151.00 (dd, 2JPC = 8.0 Hz, C3).
3
(CDCl3, ppm): δ 26.36 [d, JPC = 9.1 Hz, NCH2CH2 (pyrr)],
2
51.51 (NCH2), 46.10 [d, JPC = 4.0 Hz, NCH2 (pyrr)], 48.05
3
(C1), 118.67 (dd, JPC = 7.9 Hz, C4), 122.65 (C6), 124.31 (dd,
Spiro(propane-3-amino-1-oxy)-trans-bis{3-benzyl-3,4-dihydro-
spiro[1.3.2]benzoxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]tria-
zatriphosphorine (3i). To a THF (150 mL) solution of 3a (1.00 g,
1.59 mmol) were added sodium 3-amino-1-propanoxide (0.15 g,
1.59 mmol) and triethylamine (0.89 mL) at room temperature.
The mixture was refluxed for 26 h, and the precipitated triethy-
lamine hydrochloride and sodium chloride were filtered off.
After the solvent was evaporated completely, the oily residue
was purified by column chromatography using toluene-THF
(2:1) as an eluent (ethyl acetate, Rf = 0.31). Yield: 0.53 g (53%).
Mp: 177-179 ꢀC. Anal. Calcd for C31H33N6O3P3: C, 59.05; H,
5.27; N, 13.33. Found: C, 59.09; H, 5.32; N, 12.90. ESI-MS
(fragments were based on 35Cl): m/z 631 [M]þ. FTIR (KBr,
cm-1): ν 3364 (N-H), 3060, 3026 (C-H aromatic), 2932, 2851
(C-H aliphatic), 1239, 1184 (PdN). 1H NMR (CDCl3, ppm): δ
1.85 (m, 2H, OCH2CH2), 2.58 (bp, 1H, NH), 3.38 (m, 2H,
NHCH2), 4.11-4.43 (4H, NCH2), 4.11-4.43 (m, 4H, H1),
4.11-4.43 (m, 2H, OCH2), 6.92-7.53 (18H, Ar-H). 13C NMR
(CDCl3, ppm): δ 26.46 (d, 3JPC = 6.2 Hz, OCH2CH2) 41.47 (d,
2JPC = 3.5 Hz, NHCH2), 48.44, 48.07 (C1), 51.36, 51.79 (d,
2JPC = 3.4 Hz, NCH2), 67.46 (d, 2JPC = 6.8 Hz, OCH2), 118.91
(d, 3JPC = 7.3 Hz, C4), 119.07 (d, 3JPC = 6.9 Hz, C4), 123.21,
123.18 (C6), 123.98 (d, 3JPC = 7.3 Hz C2), 124.18 (d, 3JPC = 7.2
Hz C2), 126.81, 126.97 (C5), 128.79, 128.90 (C7), 127.54, 127.57,
128.67, 128.71, 137.83, 137.89, 138.01, 138.06 (Ar-C), 151.22
(dd, 2JPC = 6.7 Hz, C3).
3JPC = 7.4 Hz, C2), 126.71 (C5), 127.21 (C7), 128.04, 128.40,
3
128.51 (Ar-C), 138.15 (d, JPC = 7.8 Hz, Ar-C), 151.54 (dd,
2JPC = 7.5 Hz, C3).
6,6-Pyrrolidino-trans-bis{3-isopropyl-3,4-dihydrospiro[1.3.2]-
benzoxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosph-
orine (3f). The workup procedure was similar to that of com-
pound 3e, using 3b (0.90 g, 1.69 mmol) and pyrrolidine (1.11 mL,
13.52 mmol). After excess triethylamine (0.95 mL) was added to
the solution, the mixture was refluxed for another 4 h (ethyl
acetate, Rf = 0.22). Yield: 0.72 g (71%). Mp: 173 ꢀC. Anal.
Calcd for C28H42N7O2P3: C, 55.91; H, 6.99; N, 16.31. Found: C,
55.96; H, 6.79; N, 16.22. ESI-MS (fragments were based on
35Cl): m/z 602 [M]þ. FTIR (KBr, cm-1): ν 3062, 3027 (C-H
1
aromatic), 2964, 2865 (C-H aliphatic), 1242, 1178 (PdN). H
NMR (CDCl3, ppm): δ 1.22 (d, 6H, 3JHH = 7.5 Hz, NCHCH3),
1.24 (d, 6H, JHH = 7.5 Hz, NCHCH3), 1.81, 1.82 [m, 8H,
3
NCH2CH2 (pyrr)], 3.15, 3.26 [m, 8H, NCH2 (pyrr)], 4.02 (m, 2H,
3JHH = 7.5 Hz, 3JPH = 11.0 Hz, NCHCH3), 4.14 (dd, 4H, 2JHH
=
15.5 Hz, 3JPH = 7.5 Hz, H1), 6.88-7.29 (8H, Ar-H). 13C NMR
3
(CDCl3, ppm): δ 20.12 (d, JPC = 3.2 Hz, NCHCH3), 20.64 (d,
3
3JPC = 5.5 Hz, NCHCH3), 26.66 [d, JPC = 9.1 Hz, NCH2CH2
(pyrr)], 41.31 (C1), 46.24 [d, 2JPC = 4.1 Hz, NCH2 (pyrr)], 46.26
(NCHCH3), 118.55 (dd, 3JPC = 7.6 Hz, C4), 125.85 (dd, 3JPC
=
6.7 Hz, C2), 122.65 (C6), 126.60 (C5), 128.00 (C7), 151.86 (C3).
6,6-Pyrrolidino-trans-bis{3-propyl-3,4-dihydrospiro[1.3.2]-
benzoxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosph-
orine (3g). The workup procedure was similar to that of com-
pound 3e, using 3c (0.90 g, 1.69 mmol) and pyrrolidine (1.11 mL,
13.52 mmol). After excess triethylamine (0.95 mL) was added to
the solution, the mixture was refluxed for another 4 h. The
Spiro(propane-3-amino-1-oxy)-trans-bis{3-propyl-3,4-dihydro-
spiro[1.3.2]benzoxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]tria-
zatriphosphorine (3j). The workup procedure was similar to that
of compound 3i, using 3c (1.20 g, 2.26 mmol), sodium 3-amino-
1-propanoxide (0.22 g, 2.26 mmol), and triethylamine (0.64 mL)

7062 Inorganic Chemistry, Vol. 49, No. 15, 2010
Is-ıklan et al.
Table 1. Crystallographic Details
2a
2e
2f
3e
3f
empirical formula
fw
C14H13Cl4N4OP3
487.99
C8H9Cl4N4OP3
411.90
C30H45N8OP3
626.65
C36H42N7O2P3
697.68
C28H42N7O2P3
601.60
cryst syst
space group
a (A)
b (A)
c (A)
orthorhombic
Pbcn
27.1183(5)
7.8779(2)
19.4131(3)
90
triclinic
P1
monoclinic
C2/c
23.8685(4)
9.2096(1)
28.8084(4)
90
92.884(1)
90
6324.62(15)
8
0.227 (Mo KR)
1.316
5573
39 818
0.0249
50.04
0.9413/0.9582
379
0.0402
monoclinic
P21/c
10.8726(2)
26.8581(4)
12.8439(2)
90
111.767(1)
90
3483.22(10)
4
0.215 (Mo KR)
1.330
6131
24 664
0.0263
50.06
0.9482/0.9623
433
0.0399
triclinic
P1
8.5545(4)
12.1377(3)
16.6964(4)
84.618(3)
77.680(4)
74.287(5)
1629.21(11)
4
1.019 (Mo KR)
1.679
6603
7065
0.0424
52.58
8.498(2)
10.475(3)
17.969(4)
80.235(4)
79.155(3)
72.103(3)
1484.2(6)
2
0.240 (Mo KR)
1.346
5229
23 857
0.0210
50.06
R (deg)
β (deg)
γ (deg)
V (A3)
Z
90
90
4147.32(15)
8
0.814 (Mo KR)
1.563
4185
4186
0.0025
52.60
0.780/0.812
257
0.0549
μ (cm-1
F
)
calcd (g cm-1
)
no. of total reflns
no. of unique reflns
Rint
2θmax (deg)
Tmin/Tmax
no. of param
R [F2 > 2σ(F2)]
wR
0.780/0.855
364
0.0749
0.9229/0.9403
365
0.0342
0.1330
0.1840
0.1089
0.1039
0.0892
(ethyl acetate, Rf = 0.25). Yield: 0.61 g (51%). Mp: 127 ꢀC. Anal.
Calcd for C23H33N6O3P3: C, 51.68; H, 6.22; N, 15.72. Found: C,
51.32; H, 5.93; N, 15.58. ESI-MS (fragments were based on
35Cl): m/z 535 [M þ H]þ. FTIR (KBr, cm-1): ν 3274 (N-H),
3065, 3044 (C-H aromatic), 2959, 2871 (C-H aliphatic), 1235,
1168 (PdN). 1H NMR (CDCl3, ppm): δ 0.96 (t, 6H, 3JHH = 6.9
Hz, NCH2CH2CH3), 1.70 (m, 4H, 3JHH = 6.9 Hz, NCH2CH2),
1.82 (m, 2H, OCH2CH2), 2.60 (bp, 1H, NH), 3.07 (m, 4H,
NCH2), 3.40 (m, 2H, NHCH2), 4.22, 4.31 (m, 4H, H1), 4.42 (m,
2H, OCH2), 6.93-7.17 (8H, Ar-H). 13C NMR (CDCl3, ppm): δ
with benzene. The product was crystallized from n-heptane
(ethyl acetate, Rf = 0.52). Yield: 0.77 g (28%). Mp: 67 ꢀC. Anal.
Calcd for C42H39N6O3P3: C, 65.62; H, 5.08; N, 10.94. Found: C,
65.56; H, 5.18; N, 10.76. ESI-MS (fragments were based on
35Cl): m/z 769 [M]þ. FTIR (KBr, cm-1): ν 3060, 3043 (C-H
1
aromatic), 2896, 2846 (C-H aliphatic), 1240, 1172 (PdN). H
NMR (CDCl3, ppm): δ 4.09-4.45 (m, 6H, NCH2), 4.09-4.45
(m, 6H, H1), 6.96-7.41 (27H, Ar-H). 13C NMR (CDCl3, ppm):
δ 48.07 (C1), 51.40 (NCH2), 119.12, 123.27, 124.62, 126.90,
128.69, 127.55, 127.61 (Ar-C), 150.00 (C3).
3
11.57, 11.63 (NCH2CH2CH3), 21.14 (d, JPC = 11.6 Hz,
X-ray Crystal Structure Determinations. The colorless crys-
tals of compounds 2a, 2e, 2f, 3e, and 3f were crystallized by the
slow evaporation of solutions of the compounds in n-hexane at
room temperature. The crystallographic dataaregiveninTable 1,
selected bond lengths and angles are listed in Table 2, and
hydrogen-bond data are given in Table 3. Crystallographic data
for compounds 2a and 2e were recorded on an Enraf-Nonius
CAD-4 diffractometer using Mo KR radiation (λ = 0.710 73 A) at
T = 294(2) K, and absorption corrections by ψ scan18 were
applied. Crystallographic data for compounds 2f, 3e, and 3f were
recorded on a Bruker Kappa APEXII CCD area-detector dif-
fractometer using Mo KRradiation (λ= 0.71073 A) atT=150(2)
K (for 2f and 3e) and at T = 120(2) K (for 3f), and absorption
corrections by multiscan19a were applied. Structures were solved
by direct methods and refined by full-matrix least squares against
F2 using all data.19b All non-H atoms were refined anisotropically.
H-atom positions were calculated geometrically at distances of
0.93 (CH), 0.97 (CH2), and 0.96 (CH3) A (for compounds 2a and
2e) and at distances of 0.95 (aromatic CH), 1.00 (methine CH),
0.99 (CH2), and 0.98 (CH3) (for compounds 2f, 3e, and 3f) from
the parent C atoms; a riding model was used during the refinement
process, and the Uiso(H) values were constrained to be 1.5Ueq-
(carrier atom) (for CH3) and 1.2Ueq(carrier atom) (for all other H
atoms). In compound 2a, Cl atoms attached at P2 are disordered
over two orientations. During the refinement process, the dis-
ordered Cl1, Cl2, Cl10, and Cl20 atoms were refined with occu-
pancies of 0.60(3), 0.65(3), 0.40(3), and 0.35(3), respectively.
3
OCH2CH2), 26.24 (d, JPC = 6.6 Hz, NCH2CH2), 48.55
=
2
(NCH2), 49.65, 49.77 (C1), 41.20 (NHCH2), 67.00 (d, JPC
3
6.8 Hz, OCH2), 118.59 (dd, JPC = 7.2 Hz, C4), 118.67 (dd,
3JPC = 8.0 Hz, C4), 122.70, 122.75 (C6), 124.24 (dd, 3JPC = 6.3
Hz, C2), 126.40, 126.52 (C5), 127.98, 128.02 (C7), 151.14 (C3).
Spiro(propane-3-amino-1-oxy)-trans-bis{3-ethyl-3,4-dihydro-
spiro[1.3.2]benzoxazaphosphorine}[2λ5,4λ5,6λ5][1,3,5,2,4,6]tria-
zatriphosphorine (3k). The workup procedure was similar to that
of compound 3i, using 3d (0.85 g, 1.68 mmol), sodium 3-amino-
1-propanoxide (0.16 g, 1.68 mmol), and triethylamine (0.94 mL)
(ethyl acetate, Rf = 0.28). Yield: 0.45 g (53%). Mp: 124 ꢀC.
Anal. Calcd for C21H29N6O3P3: C, 49.81; H, 5.77; N, 16.60.
Found: C, 49.71; H, 5.56; N, 16.38. ESI-MS (fragments were based
on 35Cl): m/z 507 [M þ H]þ. FTIR (KBr, cm-1): ν 3264 (N-H),
3065, 3044 (C-H aromatic), 2968, 2871 (C-H aliphatic), 1240,
1177 (PdN). 1H NMR (CDCl3, ppm): δ 1.23 (d, 3H, 3JHH = 7.0
Hz, NCH2CH3), 1.25 (d, 3H, 3JHH = 7.0 Hz, NCH2CH3), 1.77
(m, 2H, OCH2CH2), 2.65 (bp, 1H, NH), 3.18 (m, 4H, 3JHH = 7.0
Hz, NCH2), 3.36 (m, 2H, NHCH2), 4.17, 4.22 (m, 4H, H1), 4.40
(m, 2H, OCH2), 6.92-7.15 (8H, Ar-H). 13C NMR (CDCl3,
ppm): δ 13.27 (d, 3JPC = 6.7 Hz, NCH2CH3), 13.42 (d, 3JPC
=
6.3 Hz, NCH2CH3), 26.49 (d, 3JPC = 6.3 Hz, OCH2CH2), 41.41
(d, 2JPC = 3.6 Hz, NHCH2), 42.58, 42.65 (NCH2), 48.08, 48.14
(C1), 67.32 (d, 2JPC = 6.8 Hz, OCH2), 118.71, 118.87 (d, 3JPC
=
4.2 Hz, C4), 123.02, 123.06 (C6), 124.39 (d, 3JPC = 3.5 Hz, C2),
126.82, 126.72 (C5), 128.24, 128.26 (C7), 151.25 (dd, 2JPC = 6.9
Hz, C3).
Results and Discussion
Tris{3-benzyl-3,4-dihydrospiro[1.3.2]benzoxazaphosphorine}-
[2λ5,4λ5,6λ5][1,3,5,2,4,6]triazatriphosphorine (4a). A solution of
1a (2.30 g, 10.80 mmol) in THF (100 mL) and triethylamine
(4.55 mL) was slowly added to a stirred solution of N3P3Cl6
(1.25 g, 3.60 mmol) in boiling THF (50 mL). The mixture was
refluxed for 21 h, and the precipitated triethylamine hydro-
chloride was filtered off. The solvent was evaporated completely,
and the oily residue was purified by column chromatography
Synthesis. The spirocyclic phosphazene derivatives
(2a-2i, 3a-3k, 4a, and 4b) have been synthesized from
(18) North, A. C. T.; Phillips, D. C.; Mathews, F. S. Acta Crystallogr.,
Sect. A 1968, 24, 351–359.
(19) (a) SADABS; Bruker AXS Inc.: Madison, WI, 2005. (b) Sheldrick,
G. M. Acta Crystallogr., Sect. A 2008, 64, 112–122.

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 7063
Table 2. Selected Bond Lenghts (A) and Angles (deg) for 2a, 2e, 2f, 3e, and 3f
2a
2e
2e0
2f
3e
3f
P1-N1
P1-N3
P1-N4
P1-O1
P2-N1
P2-N2
P2-N5
P2-O2
P3-N2
P3-N3
1.596(3) 1.588(4) 1.596(4) 1.583(2) 1.579(2) 1.593(2)
1.591(3) 1.587(3) 1.596(3) 1.575(2) 1.580(2) 1.571(2)
1.613(3) 1.617(3) 1.627(3) 1.662(2) 1.663(2) 1.649(1)
1.580(3) 1.572(3) 1.567(3) 1.626(1) 1.612(2) 1.618(1)
1.553(3) 1.555(4) 1.550(4) 1.606(2) 1.596(2) 1.588(1)
1.575(4) 1.565(4) 1.570(4) 1.591(2) 1.577(2) 1.591(1)
1.648(2) 1.642(1)
1.610(1) 1.616(1)
1.561(4) 1.568(4) 1.571(4) 1.596(2) 1.602(2) 1.605(1)
1.548(3) 1.556(3) 1.557(3) 1.610(2) 1.601(2) 1.607(1)
N1-P1-N3 113.7(2) 113.8(2) 113.2(2) 119.1(1) 117.8(1) 116.7(1)
N1-P2-N2 119.9(2) 119.5(2) 119.9(2) 115.7(1) 116.4(1) 116.6(1)
N5-P2-N6
N5-P2-O2
N7-P3-N8
N6-P3-N7
100.9(1)
101.4(1) 101.3(1)
101.4(1)
102.0(1) 101.6(1)
N2-P3-N3 119.8(2) 119.4(2) 119.8(2) 115.3(1) 114.6(1) 114.3(1)
N4-P1-O1 103.7(2) 103.6(2) 103.6(2) 103.3(1) 100.5(1) 101.3(1)
P1-N1-P2 122.5(2) 123.9(2) 118.7(2) 120.9(1) 122.1(1) 120.0(1)
P2-N2-P3 118.4(2) 119.3(2) 123.9(2) 124.3(1) 124.3(1) 121.8(1)
P1-N3-P3 124.1(2) 123.9(2) 127.2(2) 121.6(1) 123.2(1) 120.9(1)
Figure 1. 1H-decoupled 31P NMR spectra of reaction mixtures of (a) 3d
and (b) 4b.
zenes are purified by column chromatography, except the
cis isomers. In addition, N-benzyl (4a) and N-isopropyl-
substituted (4b) trispirocyclic phosphazenes are expected
to exist as cis-trans-trans or cis-cis-cis geometric
isomers. Both of them are found to be in cis-trans-trans
forms according to the 31P NMR spectra of 4a and 4b
(Figure 1b for 4b). Similar structures are observed for the
analogous compounds N-propyl- and N-ethyl-substi-
tuted trispirocyclic phosphazenes.14a
Table 3. Hydrogen-Bond Geometries (A, deg) for 2a, 2f, 3e, and 3fa
D-H
A
D-H
H
A
D
A
D-H
A
3 3 3
3 3 3
3 3 3
3 3 3
2a C8-H8A N3
0.97
0.93
0.99
0.95
0.99
0.99
0.95
1.00
2.74
2.69
2.42
2.64
2.57
2.71
2.69
2.65
3.107(6)
3.469(6)
2.969(3)
3.282(3)
3.551(3)
3.174(3)
3.456(3)
3.160(2)
103
3 3 3
C10-H10 N3
142
114
125
171
109
138
111
3 3 3
2f
C8-H8A N3
3 3 3
C2-H2 O1i
3 3 3
C21-H21A N2ii
3 3 3
NMR and IR Spectroscopy. The 1H-decoupled 31P
NMR spectral data of all of the compounds indicate that
they have spirocyclic derivatives. The spin systems are
interpreted as simple AB2, AX2, A2B, and A2X, while the
different substitution patterns at the P atoms of all of the
compounds (Table 4) give rise to one triplet and one
doublet in the 1H-decoupled 31P NMR spectra, except 4a
and 4b. The spectra of 4a and 4b exhibit a total of eight
signals for AB2 spin systems (2JPP/Δν = 1.4 for 4a and 0.5
for 4b).20 These results are unambigously in agreement
with the two kinds of P atoms present in the cyclopho-
sphazene ring.
3e C8-H8B N1
3 3 3
3 3 3
3 3 3
C19-H19 N1iii
3f
C8-H8 N3
a Symmetry codes: (i) -x, y, 1/2 - z; (ii) -x, -y, -z, (iii) x, 1/2 - y, 1/2
þ z.
the reactions of N/O-donor-type N-alkyl (or aryl)-o-
hydroxybenzylamines (1a-1e) with N3P3Cl6 in dry
THF. All of the reactions of N3P3Cl6 with the N/O
bifunctional ligands (1a-1e) appear to be regioselective
because only the spirocyclic derivatives have formed
(Scheme 1). The reactions of equal amounts of N3P3Cl6
and 1a-1e in THF with triethlyamine as an HCl acceptor
afford corresponding monospirocyclic phosphazenes
(2a-2e) at ambient temperature. The tetrapyrrolidino-
phosphazenes (2f-2i) have been obtained from the reac-
tions of 2a-2d with excess pyrrolidine. When the
reactions have been carried out with 1 equiv of N3P3Cl6
and 2 equiv of 1a-1d, corresponding dispirocyclic phos-
phazenes (3a-3d) are isolated. The 31P NMR spectra of
reaction mixtures of 3a-3d indicate that cis and trans
geometric isomers are present (Figure 1a). Only the trans
isomers are separated by column chromatography. The
bispyrrolidino dispirocyclic phosphazenes (3e-3h) are
prepared by the reactions of 3a-3d with excess pyrroli-
dine. The 3-amino-1-propanoxy derivatives (3i-3k),
which are the trispirocyclic compounds, are obtained
from the reactions of dispirocyclic phosphazenes (3a,
3c, and 3d) with sodium 3-amino-1-propanoxide. In
addition, N3P3Cl6 with excess 1a and 1b gives trispiro-
cyclic phosphazenes 4a and 4b, respectively. Figure 1b
indicates that the yield of 4b is very low; thus, it could not
have been isolated from the reaction mixture. The yields
are variable depending on mono-, di-, and trisubstitutions
of the phosphazene derivatives. All of the new phospha-
The dispirophosphazenes (3a-3h) having two equiva-
lent stereogenic P atoms are expected to exist as cis and
trans geometric isomers, which are considered as meso
and racemic forms, respectively. In addition, the trispir-
ocyclic derivatives (3i-3k) have three stereogenic P
atoms. In order to predict the stereogenic properties of
the trispirocyclic derivatives (3i-3k), the two equivalent
chiral centers P(OArN) are labeled as R/S and the other
stereogenic centers are labeled as R0/S0. Hence, the theo-
retical stereoisomeric distribution and expected geome-
trical isomers are summarized in Table 5. According to
these analyses, compounds 3i-3k have a racemate (trans)
and two meso (cis) forms. However, the only racemic
(trans) mixtures are obtained because the starting com-
pounds 3a, 3c, and 3d are racemic (trans).
As was mentioned before, the 31P NMR spectra of
reaction mixtures of 3a-3d indicate that cis and trans
geometric isomers are present. As an example, the H-
1
decoupled 31P NMR spectrum of the reaction mixture of
compound 3d is depicted in Figure 1a. The cis and trans
(20) Bovey, F. A. In Nuclear Magnetic Resonance Spectroscopy; Academic
Press: San Diego, CA, 1988; pp 159-162.

7064 Inorganic Chemistry, Vol. 49, No. 15, 2010
Is-ıklan et al.
Table 4. 31P NMR (Decoupled) Spectral Data of the Compounds (δ Reported in ppm and J Values in Hz)a
δ (ppm)
compound
spin system
PCl2
P(OArN)
P(pyrr)2
P(ORN)
2JPP (Hz)
2a
2b
2e
2f
2g
2h
2i
AX2
AX2
AX2
AB2
AX2
AB2
AB2
A2X
A2X
A2X
A2X
A2B
A2X
A2B
A2X
A2B
A2X
A2X
A2X
A2B
A2B
A2X
AB2
24.22
24.71
25.41
5.86
5.44
7.67
56.6
56.2
55.9
50.1
48.6
48.5
46.5
64.4
62.0
65.3
63.7
64.5
62.8
63.8
62.5
53.1
53.3
52.5
52.1
63.5
63.3
62.4
50.7
19.04
17.66
18.60
18.39
13.15
14.15
11.70
11.82
12.70
12.91
12.30
12.50
18.67
17.37
18.21
18.14
17.55
17.43
16.97
17.88
18.38
17.57
17.92
20.31
20.31
20.27
20.33
3a (trans)
3a (cis)
3b (trans)
3b (cis)
3c (trans)b
3c (cis)
3d (trans)b
3d (cis)
3e
3f
3g
3h
3i
29.07
33.50
28.20
28.37
28.60
28.71
28.60
28.91
21.74 (t)
21.67 (t)
21.61 (t)
21.78 (t)
20.10
19.93
20.12
3j
3k
4a
4b
AB2
45.1
a 31P NMR measurements in CDCl3 solutions at 293 K. b The 31P NMR data of 3c (trans) and 3d (trans) are taken from ref 14a.
Table 5. Theoretical Stereoisomer Distribution and the Expected Geometrical Isomers of Compounds 3a-3h and 3i-3k
compounds
stereogenic P atoms (n)
steroisomersa (2n)
chirality
geometrical isomers
3a-3h
2
1
2
3
4
RR
RS
SR
SS
racemic (lines 1/4)
meso (lines 2 = 3)
trans
cis
3i-3k
3
1
2
3
4
5
6
7
8
RRR0
racemic (lines 1/8 = 4/5)
meso1 (lines 2 = 7)
meso2 (lines 3 = 6)
trans
cis
RSR0
SRR0
SSR0
RRS0
RSS0
SRS0
SSS0
cis
a Spiro-substituted groups P(OArN) labeled as R/S and P(ORN) labeled as R0/S0.
geometric isomers of 3d are separated by preparative TLC
(Figure 2). It is observed that the trans isomer of 3d14a
yields approximately 90% and the cis isomer yields ca.
10%. The δ and J values of the cis isomers for 3a-3c are
calculated from 31P NMR spectra of reaction mixtures
(Table 4). These results are explained in terms of the
cyclophosphazene chemistry, where trans derivatives pre-
dominate over their cis isomers because of steric effects
(Figure 3a).21 Moreover, in 3e-3k, the trans isomers are
obtained because only the trans isomers of 3a-3d reacted
with pyrrolidine and sodium 3-amino-1-propanoxide
(Scheme 1). In addition, trans structures of 3e and 3f
have been verified by the crystallographic results (see the
crystallographic part).
(21) Allen, C. W. Chem. Rev. 1991, 91, 119–135.

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 7065
Figure 2. (a) 1H-decoupled 31P NMR spectra of cis and trans geometric isomers of 3d. (b) Addition ofa CSA at ca. 10:1 mole ratio showing the doubling of
signals characteristic of the racemate and meso isomers.
Figure 3. Possiblegeometricisomers of(a) di- (3a-3d) and(b) trispirocyclic(4a and 4b) phosphazenes and the propeller views of 4aand 4b. (c) Spatial view
of tetrapyrrolidinomonospirophosphazenes (3f-3i).
The stereogenic properties of compounds 3a-3k are
confirmed by 31P NMR spectroscopy upon the addition
of CSAs using the literature procedure.4b Upon titration
with CSAs, the chemical shifts change as a result of the
equilibrium between the compound and its ligand-com-
plexed form, and the changes (in ppb) at a mole ratio of
CSA-compound of 10:1 are summarized in Table 6. In
general, there are changes in both 31P NMR chemical
This is probably a result of better complexation of CSAs
with compounds 3e-3h and 3i-3k having PNR and
PORN groups, respectively, compared to compounds 3a-
3d having PCl. In addition, the spin systems of trispiro
derivatives (4a and 4b) are AB2, indicating that cis-trans-
trans geometric isomers are formed. It is found that the
orientations of the two N-alkyl (or aryl)spiro rings of 4aand
4b are the same, whereas the other is different; hence, the
whole molecule looks similar to a propeller, where the
chemical environment of P1 is different from that of P2
and P3, according to the 31P NMR results, as was observed
previously.14a Moreover, the trans trispiro compounds, 3i-
3k, also look similar to a propeller structure (Figure 3b).
In all of the spirophosphazene derivatives, the 1H and
13C NMR signals are assigned on the basis of chemical
shifts, multiplicities, and coupling constants. The assign-
ments are made unambigously by the HETCOR corre-
sponding to 1JCH between the C and H atoms (Table S1 in
the Supporting Information). As an example, the HET-
COR spectrum of 3j is depicted in Figure S1 in the
Supporting Information. The benzylic OArCH2N protons
give rise to doublets for monospirophosphazenes (2a-
2i) and multiplets for di- (3a-3i) and trispirophosphazenes
(4a). The geminal OArCH2Nprotonsof2a-2i are equivalent
2
shifts (expressed in ppb) and magnitudes of JPP. For
instance, in the cis and trans isomers of 3d, there is no
splitting of signals for the cis isomer, as was expected for a
meso compound even upon the addition of a CSA up to a
molar ratio of 50:1, but the signals of the trans isomer split
into two peaks of equal intensities corresponding to the
two enantiomers (Figure 2). The signals of the other trans
isomers (3a-3c and 3e-3i) are also separated into two
signals of equal intensities because of complexation with a
CSA (Table 6). The examples are depicted in Figures 2
and 4 for 3b and 3j, respectively. The separations in the
chemical shifts (in ppb) of the enantiomers at a mole ratio
of CSA-compound of 10:1 are summarized separately in
Table 6iii for the compounds. In general, there are greater
changes in the separations of the enantiomers for com-
pounds 3e-3h and 3i-3k than for compounds 3a-3d.

7066 Inorganic Chemistry, Vol. 49, No. 15, 2010
Is-ıklan et al.
3
to each other and give doublets, and the average JPH
Table 6. 31P NMR Parameters of Compounds 3a-3k and the Effect of a CSA on
the 31P NMR Chemical Shiftsa (X = Cl or pyrr)
value is 15.4 Hz. The geminal NCH2Ar protons of 2a and
2f also give doublets, and the average 3JPH value is 9.9 Hz.
The dispirophosphazenes (3a-3k) give highly complex
1H NMR spectra because of the diastereotopic protons.
The benzylic OArCH2N protons of these compounds give
rise to an ABX spin system because of the geminal
proton-proton coupling and the vicinal coupling with
δ (ppm)
compound
PX2
P(OArN)
P(ORN)
2JPP (Hz)
(i) 31P NMR Chemical Shifts (ppm) and Geminal PNP Coupling
Constants (Hz)
3
the 31P nucleus. The JPH values of OArCH2N protons
3a
3b
29.07
28.20
28.60
28.91
28.60
21.74
21.67
21.61
21.78
13.15
11.70
12.70
12.50
12.30
18.67
17.37
18.21
18.14
17.55
17.43
16.97
64.4
65.3
64.5
62.5
63.8
53.1
53.3
52.5
52.1
63.5
63.3
62.4
are between 6.7 and 10.0 Hz. In the 1H NMR spectra of
pyrrolidino-substituted mono- and dispirophosphazenes,
the two pyrrolidino substituents bonded to the same P
atom show two groups of NCH2 (pyrr) signals with small
separations (see the experimental part). The same situation
is also observed for NCH2CH2 (pyrr) protons (Figure 3c).
The expected carbon signals are observed from the 13C
NMR spectra of all of the compounds. The NCH2 signals
of 2a, 2f, 2h, 2i, 3a, 3e, and 3g-3k are confirmed by the
HETCOR experiments, which are 46.00-46.38 ppm for
NCH2 (pyrr), 42.51-51.73 ppm for NCH2(R)Ar, and
41.22-50.01 ppm for OArCH2. In addition, the aromatic
C atoms of the compounds are also determined by the
HETCOR experiments (Figure S1 and Table S1 in the
Supporting Information). The couplings 3JPC2, 2JPC3, and
3JPC4 of mono- and dispirophosphazenes (except 3a) give
rise to doublets and triplets. The triplets possibly depend
on the second-order effects, which are previously observed
for analogous compounds.14a In the 13C NMR spectra of
tetrapyrrolidinomonospirophosphazenes, the two pyrroli-
dino substituents bonded to the same P atom show two
groups of NCH2 (pyrr) and NCH2CH2 (pyrr) signals with
small separations (see the experimental part; Figure 3c).
The FTIR spectra of all of the phosphazene derivatives
show two medium-intensity absorption peaks at 3082-
3057 and 3048-3026 cm-1 attributed to asymmetric and
symmetric stretching vibrations of the Ar-H protons.
They display intense bands between 1261 and 1163 cm-1
related to νP-N bonds of the phosphazene ring.14a,22 The
characteristic νNH stretching bands of N-alkyl (or aryl)-o-
hydroxybenzylamines disappear in the FTIR spectra of
mono-, di-, and trispirophosphazenes. As expected,
3c
3d (cis)b
3d (trans)
3e
3f
3g
3h
3i
20.10
19.93
20.12
3j
3k
(ii) Effect of a CSA on the 31P NMR Chemical Shifts (ppb) at a 10:1 Mole
Ratio
3a
3b
3c
3d
3e
3f
3g
3h
3i
-63
130
62
44
-110
-160
-197
-160
23
-42.7
38
64.3
65.1
64.3
63.7
52.1
51.8
50.7
50.4
66.3
62.0
61.1
23
-113
-144
-372.5
-241
-129.5
-353.5
-61
-81.5
-197
-123
3j
3k
(iii) Separation of the Enantiomeric Signals (ppb) at a 10:1 Mole Ratio of
CSA-Molecule
3a
3b
3c
3d
3e
3f
3g
3h
3i
39
101
36
36
94
256
150
174
27.5
54.5
32
31
132
130
227
166
73
13
166
40
3j
3k
155
88
asymmetric and symmetric vibrations of νPCl arise for
the partly substituted spirophosphazene derivatives (2a,
2
a 202.38 MHz 31P NMR measurements in CDCl3 solutions at 293 K.
b As expected, no effect was observed up to a mole ratio of at least 50:1.
2b, 2e, 3a, and 3b) at 598-572 and 515-506 cm-1
.
Figure 4. (a) 1H-decoupled 31P NMR spectrum of compound 3j. (b) Addition of a CSA at ca. 10:1 mole ratio showing the doubling of the number of
signals, characteristic of a racemate isomer.

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 7067
Figure 7. ORTEP-327 drawing of 2f with the atom-numbering scheme.
Displacement ellipsoids are drawn at the 30% probability level.
Figure 5. ORTEP-327 drawing of 2a with the atom-numbering scheme.
Displacement ellipsoids are drawn at the 30% probability level.
Figure 8. ORTEP-327 drawing of 3e with the atom-numbering scheme.
Displacement ellipsoids are drawn at the 30% probability level.
Figure 6. ORTEP-327 drawing of 2e with the atom-numbering scheme.
Displacement ellipsoids are drawn at the 30% probability level.
X-ray Structures of 2a, 2e, 2f, 3e, and 3f. The X-ray
structural determinations of compounds 2a, 2e, 2f, 3e,
and 3f confirm the assignments of their structures from
spectroscopic data. The asymmetric unit of 2e contains
two crystallographically independent molecules. The mo-
lecular structures of 2a, 2e, 2f, 3e, and 3f, along with the
atom-numbering schemes, are depicted in Figures 5-9,
respectively. The phosphazene ring of 2e is nearly planar
[Figure S2a in the Supporting Information, j2 =-79.7(5.3)ꢀ,
θ2 = 54.9(4.7)ꢀ], while 2a, 2f, 3e, and 3f are not planar but
are in flattened-boat conformations [Figure S3a in the
Supporting Information, j2 = 96.4(1.6)ꢀ, θ2 = 58.8(1.3)ꢀ;
Figure S4a in the Supporting Information, j2 =73.6(0.4)ꢀ,
θ2 = 85.4(0.4)ꢀ; FigureS5a intheSupporting Information,
j2 = 59.9(0.6)ꢀ, θ2 = 95.6(0.5)ꢀ; Figure S6a in the Suppo-
rting Information, j2 = 147.8(2)ꢀ, θ2 = 94.8(2)ꢀ] having
total puckering amplitudes QT of 0.045(3) A (for 2e),
0.121(3) A (for 2a), 0.200(1) A (for 2f), 0.145(1) A (for 3e),
and 0.345(1) A (for 3f) (twisted boat).23
Figure 9. ORTEP-327 drawing of 3f with the atom-numbering scheme.
Displacement ellipsoids are drawn at the 30% probability level.
In monospirocyclic phosphazenes (2a, 2e, and 2f), the six-
membered rings P1/O1/C1/C6/C7/N4 and P10/O10/C10/C60/
C70/N40 (for 2e) are in boat conformations [Figure S3b in
(22) Carriedo, G. A.; Alonso, F. G.; Gonzalez, P. A.; Menendez, J. R.
J. Raman Spectrosc. 1998, 29, 327–330.
(23) Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97(6), 1354–1358.

7068 Inorganic Chemistry, Vol. 49, No. 15, 2010
Is-ıklan et al.
the Supporting Information, QT = 0.431(4) A, j2 =
-164.2(1)ꢀ, θ2 = 128.4(1)ꢀ; Figure S2b in the Supporting
Information, QT = 0.534(6) A, j2 = 100.4(1)ꢀ, θ2 =
36.6(1)ꢀ; Figure S4b in the Supporting Information, j2 =
113.6(0.1)ꢀ, θ2 = 56.1(0.1)ꢀ]. In dispirocyclic phospha-
zenes, the six-membered rings P1/O1/C1/C6/C7/N4, P2/
O2/C15/C20/C21/N5 and P1/O1/C1/C6/C7/N4, P2/O2/
C11/C16/C17/N5 of 3e and 3f, respectively, are also in
boat conformations [Figure S5b in the Supporting Infor-
mation, QT = 1.392(5) A, j2 = -122.2(1)ꢀ, θ2 = 64.6(1)ꢀ;
Figure S5b in the Supporting Information, QT = 1.235(5)
A, j2 = -74.1(1)ꢀ, θ2 = 129.8(1)ꢀ; Figure S6b in the
Supporting Information, QT =1.377(4) A, j2 = 117.9(1)ꢀ,
θ2 = 59.8(1)ꢀ; Figure S6b in the Supporting Information,
QT = 0.556(1) A, j2 = -5.9(7)ꢀ, θ2 = 47.7(5)ꢀ].
In the phosphazene rings, the endocyclic PN bond lengths
are in the ranges 1.548(3)-1.596(3) A (for 2a), 1.555(4)-
1.588(4) and 1.550(4)-1.596(4) A (for2e), 1.575(2)-1.610(2)
A (for 2f), 1.577(2)-1.602(2) A (for 3e), and 1.571(2)-
1.607(1) A (for 3f), and there are regular variations with
the distances from P1: P1-N1 ≈ P1-N3 > P2-N2 ≈
P3-N2 > P2-N1 ≈ P3-N3 for 2a and 2e and P1-N1 ≈
P1-N3 < P2-N2 ≈ P3-N2 < P2-N1 ≈ P3-N3 for 2f.
On the other hand, the exocyclic PN bonds for spirorings
are P1-N4 [1.613(3) A] (for 2a), P1-N4 [1.617(3) A] and
P10-N40 [1.627(3) A] (for 2e), P1-N4 [1.662(2) A] (for
2f), P1-N4 [1.663(2) A] and P2-N5 [1.648(2) A] (for 3e),
and P1-N4 [1.649(2) A] and P2-N5 [1.642(2) A] (for 3f)
(Table 2). The average P-N bond lengths in the phosp-
hazene rings are 1.570(4) and 1.573(4), 1.594(2), 1.589(2),
and 1.593(1) A, which are shorter than the average exocyclic
P-N bonds of 1.622(3), 1.652(2), 1.650(2), and 1.649(2) A
for 2e, 2f, 3e, and 3f, respectively. In the phosphazenes, the
P-N single and double bonds are generally in the ranges
of 1.628-1.691 and 1.71-1.604 A, respectively.24 In recent
years, natural bond orbital (NBO) and topological elec-
tron density analyses have been used to investigate the
electronic structures of phosphazenes.24 Phosphazene
bonding alternatives are evaluated using NBO and nega-
tive hyperconjugation, and ionic bonding plays an im-
portant role for the P-N bond formation and is critical to
the description of P-N bonding in these molecules. As a
result of these investigations, ionic bonding is found to be
the dominant feature, and the multiple-bond character
can be attributed to the presence of negative hyperconju-
gation.24,25
As can be seen from Table 2, in tetrachloro monospiro-
cyclic phosphazenes (2a and 2e), the endocylic N1-P1-
N3 (R) angles are narrowed, while the P1-N3-P3 (β)
angles are considerably expanded with respect to the corres-
ponding values in the “standard” compound, N3P3Cl6.
In N3P3Cl6, the R and β angles are 118.3(2) and 121.4(3)ꢀ,
respectively.26 On the other hand, in tetrapyrrolidino
monospirocyclic phosphazene (2f), the endocylic N1-
P1-N3 (R) angle is slightly expanded and the P1-N3-P3
(β) angle has almost the same value with the standard
compound, whereas the P2-N2-P3 angle is highly expanded.
(24) Chaplin, A. B.; Harrison, J. A.; Dyson, P. J. Inorg. Chem. 2005, 44,
8407–8417.
(25) Krishnamurthy, S. S. Phosphorus, Sulfur Silicon Relat. Elem. 1994,
87, 101–111.
(26) Bullen, G. J. J. Chem. Soc. A 1971, 1450–1453.
(27) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565–566.

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 7069
Table 8. In Vitro Antimicrobial Activities of Compounds 2f-2i, 3e-3i, and 3k (MIC Values)a
MIC values
microorganism names
2f
2g
2h
2i
3e
3f
3g
3h
3i
3k
S. aureus ATCC 25923
P. aeruginosa ATCC 27853
P. vulgaris ATCC 8427
E. coli ATCC 35218
E. coli ATCC 25922
E. feacalis ATCC 292112
B. cereus NRRL-B-3711
B. subtilis ATCC 6633
C. albicans
156.25
NT
NT
NT
NT
2500
156.25
625
0.148
0.170
19.53
2500
NT
9.76
625
19.53
625
625
2500
39.06
19.53
0.127
0.068
19.53
41.66
NT
1250
41.66
156.6
19.53
78.12
NT
312.5
NT
NT
NT
NT
NT
NT
NT
NT
NT
NT
NT
- NT
NT
NT
NT
NT
NT
NT
312.5
NT
312.5
312.5
NT
78.12
NT
NT
625
NT
NT
NT
NT
NT
1250
NT
NT
1250
NT
NT
2500
312.5
NT
NT
NT
2500
2500
2500
NT
NT
41.66
19.53
2500
2500
0.113
0.133
NT
NT
312.5
39.3
NT
19.53
19.53
NT
C. tropicalis
NT
NT
NT
NT
NT
a NT: not tested.
In dispirophosphazenes (3e and 3f), the R angles
[N1-P1-N3 117.8(1)ꢀ and N1-P2-N2 116.4(1)ꢀ for 3e
and N1-P1-N3 116.7(1)ꢀ and N1-P2-N2 116.6(1)ꢀ for
3f] are slightly narrowed, while the β angles are slightly
expanded only for 3e with respect to the corresponding
values in N3P3Cl6. It is noteworthy that the endocyclic
N-P-N angles of centered P atoms, which are bonded to
pyrrolidino groups in 2f, 3e, and 3f, are considerably
narrowed [the average value of these angles is 115.0(1)ꢀ].
All of these results indicate that variations in the angles
found in phosphazenes could be attributed to the sub-
stituent-dependent charge at the P centers and negative
hyperconjugation.24
against E. coli (ATCC 25922). Compounds 2f-2i and 3k
are active against E. fecalis. Meanwhile, the compounds
are very active against B. cereus (except 3f and 3i) and
B. subtilis (except 3f). In addition, 2f, 2g, and 2g are also
found to be active against yeast strain of C. tropicalis
(ATCC 13803) and C. albicans (ATCC 10231). According
to these findings, one can conclude that the compounds
have strong antimicrobial effects on tested bacteria. The
most susceptible strains are the Gram-positive B. subtilis,
B. cereus, and S. aureus.
Consequently, pyrrolidine derivatives are widespread
structural features of natural and biologically designed
active molecules, and also they can be used for pharma-
ceutical purposes.28 So, pyrrolidine is especially chosen as
a substituent in this study. On the other hand, there are
several studies about the antimicrobial/antibacterial ac-
tivity of phosphazenes,10 but these compounds are not
analogous compounds for comparison with pyrrolidino-
substituted phosphazenes tested in this study. In addition,
it is shown that the tetrapyrrolidinoferrocenylphospha-
zenes have antibacterial and antifungal activity.5c However,
pyrrolidino-substituted N/O spirocyclicphosphazenes
(2f-2i, 3e-3i, and 3k) exhibited better activity with
respect to the mono- and bisferrocenyltetrapyrrolidinop-
hosphazenes.5c
The packing diagrams of 2a, 2e, 2f, 3e, and 3f are given
in Figures S2c-S6c in the Supporting Information, re-
spectively. Compounds 2a, 2f, 3e, and 3f have intramole-
cular C-H N hydrogen bonds (Table 3). In the crystal
3 3 3
structure, compounds 2f and 3e have intermolecular
hydrogen bonds, while compound 2f also has an inter-
molecular C-H O hydrogen bond (Table 3). In com-
3 3 3
pound 3e, intermolecular C-H N hydrogen bonds
(Table 3) link the molecules into infinite chains along
3 3 3
the c axis (Figure S5c in the Supporting Information). In
O
compound 2f, intermolecular C-H N and C-H
3 3 3
3 3 3
hydrogen bonds (Table 3 and Figure S4c in the Support-
ing Information) link the molecules into a 2D network.
Antimicrobial Activities. A screening of antibacterial
activities with eight bacteria [Staphylococcus aureus (ATCC
25923), Pseudomonas aeruginosa (ATCC 27853), Escher-
ichia coli (ATCC 35218), E. coli (ATCC 25922), Bacillus
subtilis (ATCC 29213), B. cereus (NRLL B-3008), Proteus
vulgaris ATCC 8427, and Enterobacter fecalis (ATCC
292112)] was performed; the antifungal activity (Candida
albicans and C. tropicalis) was also assessed, and the
minimum inhibitory concentrations (MICs in mg/mL)
were determined (Tables 7 and 8). MICs were found for
2f-2i, 3e-3i, and 3k, ranging from 9.76 to 2500 mM.
Compound 2h demonstrates the most inhibitory activities
with MIC values of 9.76 mM. Table 7 shows the anti-
microbial effects of compounds 2f-2i, 3e-3i, and 3k. All
of the compounds (except 3f) exhibit antimicrobial acti-
vity. Compounds 2f-2i, 3e, 3h, and 3k inhibit S. aureus.
Compound 2h is the most effective one, showing activity
as much as control antibiotics. Compounds 2g and 2h
reveal activities against P. aeroginosa. Only 2h and 3k
reveal activities against P. vulgaris. Compounds 2h, 2i,
and 3g are active against E. coli (ATCC 35218). On the
other hand, compounds 2g, 2h, 2i, 3h, and 3i are active
Interaction with pUC18 plasmid DNA and Restriction
Enzyme Digestion. In order to find out whether 2f-2i,
3e-3i, and 3k bind and induce conformational changes
on the DNA helix, their capacities to remove and reverse
the supercoiling of closed circular pUC18 DNA as
assessed by electophoretic mobility on agarose gels by
incubating plasmid DNA with decreasing concentrations
of the compounds were investigated. Figure 10 shows the
electophoretic mobility pattern of form I (ccc) and form II
(oc) of pUC18 plasmid DNA after incubation at a range
of concentrations with 2f-2i, 3e-3i, and 3k for 24 h. In
the electrophoretograms, the untreated pUC18 plasmid
DNA is used as a control. Lines 2-6 refer to mixtures of
DNA of varying concentrations of compounds ranging
from 5000 to 156 μM (line 2, 5000 μM; line 3, 2500 μM;
line 4, 1250 μM; line 5, 625 μM; line 6, 312 μM; line
7, 156 μM). When pUC18 plasmid DNA interacts with
decreasing concentrations of compounds 2f-2i, 3e-3i,
and 3k, a decrease in the mobility of form I is observed at
two (three for 2h, 2i, 3f, 3g, 3i, and 3k) high concentrations.
(28) (a) Mitchell, R. E.; Teh, K. L. Org. Biomol. Chem. 2005, 3, 3540–
3543. (b) Bellina, F.; Rossi, R. Tetrahedron 2006, 62, 7213–7256.

7070 Inorganic Chemistry, Vol. 49, No. 15, 2010
Is-ıklan et al.
Figure 10. Gel electrophoretic mobility of pUC18 plasmid DNA when incubated with different concentrations of compounds 2f-2i, 3e-3i, and 3k.
Concentrations (in μM) are as follows: line 1, untreated pUC18 plasmid DNA; line 2, 5000; line 3, 2500; line 4, 1250; line 5, 625; line 6, 312; line 7, 156.
Figure 11. Electrophoretograms for the HindIII digested mixtures of pUC18 plasmid DNA after their treatment with various concentrations of
compounds 2f-2i, 3e-3i, and 3k. Concentrations (inμM) are as follows: line 1, untreated pUC18 plasmid DNA; line 2, 5000; line 3, 2500; line4, 1250; line5,
625; line 6, 312; line 7, 156; line 8, pUC18 plasmid DNA linearized by HindIII. Roman numerals I, II, and III indicate form I (covalently closed circular),
form II (open circular), and form III (linear) plasmids, respectively
Figure 12. Electrophoretograms for the BamHI digested mixtures of pUC18 plasmid DNA after their treatment with various concentrations of
compounds 2f-2i, 3e-3i, and 3k. Concentrations (inμM) are as follows: line 1, untreated pUC18 plasmid DNA; line 2, 5000; line 3, 2500; line4, 1250; line5,
625; line 6, 312; line 7, 156; line 8, pUC18 plasmid DNA linearized byBamH. Roman numerals I, II, and III indicate form I (covalently closed circular), form
II (open circular), and form III (linear) plasmids, respectively
Compounds 2f, 2h, 3g, and 3i decrease the intensities of
the form I bands. The increase in the intensities of the
form I band is observed for 2i at three high concentra-
tions. Compound 2g shows a coalescense point and
indicates a strong unwinding of form I. In general,
compounds are active at three high concentrations.

Article
In order to find out whether compounds, 2f-2i, 3e-3i,
Inorganic Chemistry, Vol. 49, No. 15, 2010 7071
from that of P2 and P3. In addition, 4a and 4b exist as
cis-trans-trans geometric isomers. Among the phospha-
zenes tested, all of the compounds (except 3f) have strong
antimicrobial activities. MICs determined for these com-
pounds range from 9.76 to 2500 mM. Compound 2h demon-
strates the most inhibitory activities, with MICs ranging from
9.76 to 2500 mM. Biological activity studies suggest that they
may serve as potential candidates of new antimicrobial
agents. On the other hand, compound-DNA interaction
studies show that the compounds cause changes in the
mobility of the form I band of plasmid DNA. The com-
pounds, except 2g, are found to be similar in their ability to
cause unwinding of supercoiled form I pUC18 plasmid DNA
and prevent BamH1 and HindIII digestion, in their activity
and binding with DNA.
and 3k show affinity toward guanine-guanine and/or
adenine-adenine nucleotides of DNA, restriction analy-
sis of the compound-DNA adducts digested with Hind-
III and BamHI enzymes was performed. HindIII and
BamHI enzymes bind at sites 50-A/AGCTT-30 and 50-G/
GATCC-30 of DNA, cleave these sequences, and convert
forms I and II DNA to the linear form III DNA. All of the
compounds, except 2g, prevent digestion with HindIII
and BamHI enzymes; this may be due to the binding of the
compounds to the DNA (Figures 11 and 12).
Conclusions
The spirocyclic phosphazene derivatives containing 1,3,2-
oxazaphosphorine rings are very limited in the literature. In
this study, new mono- (2a-2i), di- (3a-3k), and trispirocyc-
lic (4a-4d) phosphazene derivatives with chiral properties
(except monospirocyclic ones) are obtained. Compounds
3a-3h have two stereogenic P atoms. They are expected to
be in the cis (meso) and trans (racemic) geometric isomers.
Only the trans isomers of 3a-3d are isolated and reacted with
pyrrolidine and sodium 3-amino-1-propanoxide to give
3e-3k. In addition, the enantiomers of chiral phosphazenes
are determined by changes in the 31P NMR spectra upon the
addition of CSAs. In general, there are changes in both δP
shifts and 2JPP coupling constants. In the trans trispirocyclic
compounds (3i-3k), there are three stereogenic P atoms. The
molecular structures of 3i-3k, 4a, and 4b look similar to a
propeller, where the chemical environment of P1 is different
Acknowledgment. The authors acknowledge the Scien-
tific and Technical Research Council of Turkey (Grant
106T503). T.H. is indebted to Hacettepe University,
Scientific Researchs Unit (Grant 02 02 602 002) for
financial support.
Supporting Information Available: Listings of the HETCOR
spectrum of 3j (Figure S1), ring conformations, crystal packing
diagrams (Figures S2-S6), and X-ray crystallographic files in
1
CIF format for compounds 2a, 2e, 2f, 3e, and 3f, 2D H-13C
HETCOR correlation for compound 3j (Table S1), antimicro-
bial activities (section S1), and DNA and compound interac-
tions (section S2). This material is available free of charge via the
Internet at http://pubs.acs.org.