close

Вход

Забыли?

вход по аккаунту

?

Spherical Cyclophosphazene Dendrimers to the Fifth Generation.

код для вставкиСкачать
COMMUNICATIONS
[l] K. C. Nicolaou, W.-M. Dai, Arigew. Cheni. 1991. 103. 1453: Angew. Chem. h i .
Ed. Engl. 1991. 30. 1387.
[2] J. W. Lown. Chem/racrs 1993. 6, 205.
[ 3 ] P. E. Nielsen, Bioconjugute Chem. 1991. 2. 1.
[4] E. Uhlmdnn. A. Peyman, Chem. Rev. 1990, 90, 543.
[5] P. B. Dervan in Nucleic Acids und Molecular Biology, Vol. 2 (Ed.: F. Eckstein.
D. M. J. Lilley), Springer. Heidelberg. 1988, pp. 49-64.
[6] P. B. Dervan in Oligodeo~ynucleoridestAnti.wnsr o/Gene E.rpression (Ed.: J. S.
Cohen), CRC Press. Boca Raton. FL, 1989. pp. 197-210.
[71 C. Helene. J:J. Toulme in Oligodeo.~ynirc/rotid',~:
Antisense of Gene Erpres.rion
(Ed.: J. S. Cohen), CRC Press, Bocd Raton, FL. 1989. pp. 137-172.
[8l M. D. Lee. K. M. Manning, D. R. Williams, N. A. Kuck, R. T. Testa, D. B.
Borders. J Anrrbior. 1989. 42. 1070.
[91 T. Li, Z. Zeng. V. A. Estevez, K.-U. Baldenius. K. C. Nicolaou. G. F. Joyce, J.
Am. Chem. Soc. 1994, 116, 3709.
[lo] K. C. Nicolaou, S:C. Tsay, T. Suzuki, G. F. Joyce, J. Am. Chem. Soc. 1992,
114. 7555.
[Ill L. Gomez-Paloma. J. A. Smith. W J. Chazin, K. C. Nicolaou, J. Am. Chc>m.
Suc. 1994, 116, 3697.
[I21 K . C. Nicolaou, R. D. Groneberg, T. Miyazaki, N. A. Stylianides. T. J. Schulze,
W. Stahl, J. Am. Chem. Soc. 1990, 112.8193. A second synthesis of 1 appeared
later: R. L. Halcomb, S. H. Boyer, S. J. Danishefsky. Angru. Chem. 1992, 104,
314; Angrw. Chern. Inl. Ed. Engl. 1992, 31, 338.
[I31 S. N. Ho, S. H. Boyer, S. L. Schreiber. S. J. Danishefsky. G. R. Crabtree, Prot..
Nail. Acad. Sci. USA, 1994, 91, 9203.
[14] The TCCT site may be interchanged with a TCTC or a TTTT site, see refs.
[9- 121, and references therein.
[15] S. L Walker, A. H. Andreotti. D. E. Kahne, Tetrahedron 1994. 50,
1351.
[16] J. Aiydr. S. J. Danishefsky, D. M. Crothers, J. A m . Chem. Soc. 1992, 114.
7552.
[I71 K. C. Nicolaou, C. W. Hummel. M. Nakada. K . Shibayama, E. N. Pitsinos, H.
Saimoto, Y Mizuno, K.-U. Baldenius. A. L. Smith, J. Am. C h m . Soc. 1993.
115. 7625.
[la] All new compounds provided satisfactory spectroscopic and analytical
data.
[I91 Selected spectroscopic and physical properties of 2.4, and 5.2: Colorless solid:
R, = 0.52 (silica gel. MeOH/CH,CI, l;4); [ZIP= 41 (c = 0.50, MeOH); IR
= 3600-3200,2973.2933,1673,1455,1416,2392.131Y,
1239.1100,
(neat):
1066. 959 c m - ' ; 'H N M R (500 MHz. CD,OD): 6 = 5.62 (br. s, 2H. D-I),
CHHCH,OCH,CHH), 3.81 (s, 6H, CH,O), 3.77 (s, 6H, CH,O). 3.70 (dd,
J=9.0,9.0Hz,2H.D-4),3.67(dd,J=10.5,2.5Hz.2H,B-4),3.63-3.52(m,
8H. D-3, CHHCH,OCH,CHH), 3.39 ( s , 6 H . C H 3 0 ) . 3.32(m,2H. E-4), 3.16
(s. 6 H , CH,O). 2.31 (s, 6H. ArCH,), 2.23 (m, 2 H , E-2,,), 1.95 (m, 4 H ,
B-2,,,..),1.43(d,J=7.0H~,6H,A-6),1.28(d,J=6.5Hz,6H,B-6),1
16(d,
J = 6.5 Hz, 6H. D-6), 0.98-0.90 (m, 72H. 8 x Si(CH,CH,),); MS (positive
2 Na+], calcd for C,,,H,,,I,N,O,,S,Si,:
ion ESI): rnji 3394: [M,,,-2H+
3394.
The details of these NMR studies will be reported elsewhere in due
course.
We thank Drs. Peter Vogt and Chen LIUfor their results. These and related
studies will he reported in due course.
+
Spherical Cyclophosphazene Dendrimers to the
Fifth Generation**
Franqois Sournies, Franqois Crasnier,
Marcel Grdffeuil, Jean-Paul Faucher, Roger Lahana,
Marie-Chris tine Labarre, and Jean-Frangois Labarre*
Dendrimers, that is, highly branched functionalized molecules
formed by iterative reaction sequences, constitute a definite
breakthrough into generations of new materials and are attracting considerable attention in organic, supramolecular, and polymer chemistry.['] Only few of these macromolecules incorporate
main group elements such as silicon,[21germanium,[31or phosp h o r ~ ~ ,and
[ ~ ] only phosphorus dendrimers having charges
within the cascade structure had been de~cribed'~]
till very recently when two kinds of neutral phosphorus dendrimers were
reported concomitantly by Majoral et al.['] and by our
'I Majoral's dendrimers have a structure resembling a
group.[6,
5.43(br.s,2H,E-l),5.09(br.d,J=lO.OHz,2H,B-l),4.49(br.s,2H.D-2).
cauliflower, with SPCI, as the core and possess 46 pentavalent
4.38 (d, J = 8.0Hz, 2 H , A-l).4.25(br. s, 2H. B-3). 4.18 (dq, J = 9.5.6.0Hz.
2H. D-5), 4.06 (dq, J=10.5. 6.5Hz. 2H. B-5). 4.01-3.92 (m. 4H. E-5.
phosphorus atoms and 48 terminal functions (aldehydic groups
CHHCH,OCH,CHH), 3.96 (dd, J = 9.5, 9.5 Hz. 2H. A-3), 3.92 (s. 6H.
or phosphorus-chlorine bonds; molecular weight 1 1 268 or
CH,O), 3.87 (s, 6 H , CH,O). 3.84-3.71 (m, 12H, B-4. D-3, E-5'.
15 381). His group is now synthesizing further generations havCHHCH,OCH,CHH). 3.69(dq.J = 9.5. 6.5 Hz,2H,A-5).3.61 ( d d , J = 9.5,
ing up to 384 functional groups (molecular weight 94 146).C8I
9.5 Hz. 2 H . D-4), 3.57 (s. 6H. CH,O), 3.42 ( s , 6 H . CH,O), 3.37 (dd, J = 9.5,
8.0 Hz, 2H, A-2). 2.89 (m. 2H. E-4). 2.80 (m. 4 H , 2 x CH,CH,N), 2.47 (m,
Our dendrimers are spherical architectures which were de2H. E-2,J. 2.38 (s. 6 H , ArCH,), 2.28 (dd. J = 9.5, 9.5 Hz, 2H. A-4). 2.00 (m,
signed from previously skillfully synthesized D,, cyclophos2H. B-2,,). 1.79 (m, 2 H , B-2,,,). 1.50 (m, 2H. E-2,,), 1.41 (d, J = 6.5 Hz. 6 H ,
phazene cores. Indeed, we recently reportedL6.'I pure cyclophosB-6), 1.39 (d, J = 6.5 Hz, 6H. A-6), 1.28 (d, J = 6.0 Hz. 6H, D-6), 1.22 (br. t,
phazenic hexapodanes (termed sexapus because of the six
J = 6 . 8 Hz, 6 H , 2xCH,CH2N); " C N M R (125MHz, CD,OD): 6 =194.1,
153.2, 152.0, 144.6, 134.5, 132.5, 99.8, 94.2. 81.7. 80.6, 77.1, 72.6. 72.3, 72.1.
tentacles, in analogy to an octopus) synthesized through a re71.6, 71.3, 70.5, 69.4, 69.3. 69.3, 68.2, 62.3, 61.5, 59.9, 57.5. 56.2, 42.7, 41.6,
giospecific peraminolysis of hexachlorocyclotriphosphazene
39.0, 35.2, 25.7, 19.4, 18.8. 14.7. 10.0; MS (positive ion EN): mjr 1996:
(N,P,CI,) by long-chain diamines, H,N(CH,),NH, ( n 2 6), on
[ ( M + H)i],calcdforC,,H,2412N40,,S,:
1996.-4: Colorlesssolid; R, = 0.15
ALPOT (50: 1I), that is, on alumina impregnated with a certain
(silica gel, 2 % MeOH in CH,CI,): [m];' = - 21 ( c = 1.7, CHCI,): IR (neat):
C = 2953, 2926, 2876, 1694, 1682, 1454, 1260. 1084. 1017 cm-'; ' H NMR
amount of potassium hydroxide.['] These sexapus units are 3-di(500 MHz, [DJDMSO, 80°C): 6 ~ 7 . 8 (d,
4 J =7.5 Hz. 2H, FMOC), 7.63 (d.
mensional polyfunctional cores suitable for generating spherical
J =7.5 Hz, 2H, FMOC), 7.39 (dd, J =7.5, 7.5 Hz, 2H. FMOC), 7.31 (dd,
cyclophosphazene dendrimers (that is, resembling the structure
J =7.5, 7.5 Hz, 2H. FMOC), 5.42-5.37 (m, 2 H , B-I, D-1). 5.08 (br. s. 1 H.
of a dry dandelion flower and not of a cauliflower like Tomalia's
E-I), 4.75 (9. J = 6.5 Hz, 1 H, A-5), 4.47-4.38 (m, 5H, A-1, 8-3, D-2. CH,FMOC). 4.28 (t. J = 6.0 Hz, 1 H, benzyl. FMOC), 4.22 (br. s. 1 H, A-3). 4.05
dendrimers['I). An attempt at the production of spheroid den(dq,J=9.0,6.5HZ,1H,D-5),4.00(dq,J=10.0,6.5Hz.lH,B-5),3.84-3.72
drimers belonging to carbon chemistry was recently made by
~
(m, SH, A-2. E-3, E-5. E-S, CHHCH,OCH,CH,OH). 3.X2 (s, 3H, CH,O).
3.78 (s. 3H, CH,O), 3.70 (dd, J = 9.0, 9.0 Hz. 1 H, D-4). 3.68 (dd, J =10.0,
2.5 Hz, 1 H, 8-41? 3.66-3.42 (m%8 H . D-3, CHHCH,OCH,CH,OH). 3.40 (s.
['I
Dr. JLF. Labarre, Dr. F. Sournies. Dr. F. Crasnier, Dr. M. Graffeuil,
3H.CH,O),3.31(m,lH,E-4),3.17(s,3H,CH,O),2.31(s,3H,ArCH,),2.24 Dr. J.-P. Faucher, Dr. M.-C. Labarre
Institut de Chimie Molkculaire Paul Sabatier, Ldboratoire Structure & Vie
Universite Paul Sabatier. 118 route de Narbonne
F-31062 Toulouse Cedex (France)
Telefax: Int. code + 61 251733
Dr. R. Lahana
Oxford Molecular SA. X-Pole. Ecole Polytechnique
F-91128 Pabaiseau Cedex (France)
[**I On the Scent of Dandelion Dendrimers. Part 3 . The authors are greatly indebt7.38(dd.J=7.5.7.5H~.4H.FMOC).7.30(dd,J=7.5.7.0Hz,4H.FMOC). ed to the Universite Paul Sabatier (ACRU 1993-1994) and the French Minis5.42-5.37 (m, 4 H , B-1, D-I), 5.08 (br. s. 2H. E-I), 4.73 (4, J =7.0 Hz, 2H.
tery of Education (66.71.50) for their generous financial support to this work.
A-5). 4.45-4.37 (m, IOH, A-I, 8-3. D-2. CH,-FMOC). 4.26 (t. J = 6.0 Hz,
Sincere thanks are due to Dr. Suzanne Richelme who performed DCIINH,
2H.benzyl. FMOC).4.22(br.s,2H.A-3),4.05(dq.J=9.0,6.5Hz,2H,D-5).
and FAB measurements and to Dr. Akdin Dall'Ava for 3'PNMR spectra.
3.99(dq,J=10.5.6.5Hz,2H.B-5),3.83-3.73(m,10H,A-2,E-3,E-5,E-5', Part 2: [7].
(m.1 H. E-2,,), 1.98 (m, 2H, B-2eQ.J. 1.44 (d. J = 6.5 Hz. 3H, A-6), 1.29 (d.
J = 6 . 5 H z , 3H, 8-6) 1.17 (d, J = 6 . 5 H z . 3H. D-6). 0.99-0.91 (m. 36H,
4 x Si(CH,CH,),), 0.67-0.58 (m. 27H. 4 x Si(CH,CH,),, CH,CH,N): MS
(positive ion ESI): m/r 1750; [ ( M + Na)']. calcd for C,,H,,,IN,O,,SSi,:
1750. - 5: Colorless solid; R, = 0.46 (silica gel, ether/petroleum ether l / l ) :
[ZIP= 14 (c = 0.99. CHCI,); IR (neat): i. = 2954, 2936. 2876, 1700, 1456.
1417, 1239, 1140, 1085, 1016. 1004cm-', 'H NMR (500MHz, [DJDMSO,
8O'C):S =7.83(d.J =7.5 Hz,4H, FMOC),7,62(d, J =7.0 Hz,4H, FMOC),
~
578
8
VCH Verlugsgrsrllschaft mhH. 0-69451 Weinheim. 1995
0570-0833~9SjOSOS-0578
$10.00+ ,2510
Angew. Chem. Inr. Ed. Engl. 1995, 34, No. 5
~~
~
COMMUNICATIONS
~
Frechet['*' "through the linkage of two cauliflowers by their
stumps". but such dendrimers are just spheroids and not, in a
strict sense, spherical objects.
Scheme 1 shows that the amino end groups of tentacles in
sexapus 1 a are accessible to further nucleophilic attacks. Our
dendrimer design is based on a two-step process. In the first step
N,P,CI, flagstones (pentafunctional fans) are grafted at the end
of each tentacle to give compounds 1 b (or generation 1) and in
the second step the chlorine atoms of the N,P,Cl, flagstones are
all substituted by a new set of long-chain diamines (H,N(CH,),NH,, I? 2 6) as linkers to give compounds 2 a . In other words,
the linkage of such N,P,Cl, flagstones on sexapus cores leads to
first-generation dendrimers, in which the number of linkers for
further extension is multiplied by five with respect to the starting
N,P,CI, itself. Thus, every two-step procedure from 1b yields a
new generation. In this paper we report on the synthesis and
structural characterization of such dendrimers from sexapus
cores till the fifth generation (5b). Moreover, the chemical properties of dendrimers of the first (1 b) and second (2 b) generations
were investigated to discover more about the point where steric
congestion and/or loss of solubility will prevent further growth
of the dendrimer.
The expected first-generation dendrimers 1b are actually polybino structures," and we demonstrated previously that the synthesis of such two-ring, bridged assemblies requires the use of
polar solvents. In other words, toluene (which was used to obtain
H2N
Scheme 2. A general pattern for the step by step synthesis of dendrimers to the fifth
generation. Left are the formula numbers, right the molecular weights M (for n = 6)
of the first, second. third. and fifth generations, and in the middle the structural
formulas of the added unit (top) and number of functionalities (bottom).
cores 1a) is no longer the right solvent for reaction (a) and has
to be replaced by diethyl ether. In addition, Et,N was required
NH
NH
vvv
n
n
la
NH
x v v v
NH
/
NH
WX
n
n
X
lb
Scheme I . Sexapus cores ( l a ) , the precursors of dendrimers of the first generation (1 b).
Zigzag linesmarked with nrepresent (CH,),chains within the-HN(CH,).NH, tentacles. The
central N,P, ring has the bow-tie form proposed by R. A. Shaw.
Ai?,qiw. Chem. In!.
Ed. Engl. 1995. 34. No. 5
for scavenging hydrogen chloride. Incidentally,
when ALPOT(50: 11) is used, irrespective of
the choice of solvent, no eluent can be found to
remove the final products from the solid support.
Further elaboration to cascade molecules of
the second (2b), third (3b), fourth (4b), and
fifth generation (5b) is accomplished by repetition of the two-step procedure (Scheme 2). In
each step, reactants are introduced in the correct stoichiometry. The only by-products are
hydrogen chloride and the related hydrochlorides! All the compounds of the generations are
stable and perfectly soluble in a wide variety o f
organic solvents (for example, chloroform, diethyl ether). All the intermediate compounds (2 a, 3 a , 4 a ,
and 5 a) with amino groups at the periphery are no longer
soluble in the organic solvents but are noticeably soluble
in water. All the dendrimers were characterized by N M R
and IR spectroscopy, and elemental analysis. Mass spectrometry (FAB or electron spray) was useful up to 2a.
Remarkably, the construction o f each generation
could be easily followed by "P N M R spectroscopy: all
phosphorus centers of each generation are distinguishable by their 31PN M R chemical shifts and by the intensities of the different signals.
In the following we shall describe various cascade molecules obtained from sexapus l a, n = 6. Physical data of
the reactants for the synthesis of the first-generation dendrimers l b are as follows: for the sexapus: S(31P)=
18.4(s), m /z ( M E ' ) 826, v(NH,) 3410cm-' (br.); for
N,P,CI,: S(3'P) = 20.1(s), rnjz ( M H ' ) 345, v, (PC1) =
599, v,, (PCl) = 520 cm-'. Two days later both singlets at
6 18.4 and 2O.l had disappeared, and the signals of an
A,B system (peripheral PCI, and peripheral PCINH) to-
cl VCH Rda~sgrsellschaftmhH, 0-69451 Wrinheim,1995
0570-0833/95/0505-057Y$ 10.OOf ,2510
519
COMMUNICATIONS
gether with the singlet of the phosphorus atoms from the core
are revealed. Simultaneously, the symmetric and asymmetric
PCI stretching modes from N,P,Cl, at 599 and 520 cm-’, respectively, are replaced by modes at 589 and 513 cm-‘, which
are characteristic for the first-generation dendrimers 1 b. Moreover, the NH, stretching frequency of the starting sexapus at
3410 cm-’ is no longer observed, but a unique N-H stretching
frequency remains at 3234 cm- In other words, ’P NMR and
FTIR spectroscopies are sufficient to characterize 1 b, n = 6.
The second-generation dendrimers 2 b are obtained through
nucleophilic substitution of the 30 chlorine atoms of the firstgeneration 1 b by 30 diamino groups (leading to 2a) and subsequent grafting of 30 N,P3C1, moieties on the ends of the 30 new
tentacles. Because this aminolysis on ALPOT(50: 11) gave very
poor yields (<25 %), we chose Et,N as scavenger for HCI and
a polar solvent such as Et,O. After 48 h the resulting light yellow syrupy oils, which are actually Et,O-clathrates, are stirred
(about 12 h) with large excess of n-heptane to afford the declathrated species as white powders.
The physical data for 2a are as follows: d(,’P) = I 8 3 (s,
major signal), 19.3, 22.0 (each s, minor signals), v,(NH,) =
3393 cm-‘, v,,(NH,) = 3333cm-’, 6(NH,) =I583 cm-’.
The transformation from 2a to 2b occurs upon grafting
30 N,P3C15 moieties on the ends of the 30 tentacles. Modifications to ,‘P NMR and FTIR data are strictly identical to the
ones we described above when comparing the spectra from the
sexapus 1 a and the first-generation dendrimers 1 b, that is, replacement of a 31PNMR singlet by an A,B system together with
emergence of v,(PCl) and v,,(PCl) stretching frequencies.
The purity of the products at each step was checked by thin
layer chromatography with toluene/CCI, (3: 1) as eluent. A
unique spot was observed till the third-generation 3 b, where a
minor side-spot appeared. Apparently this impurity corresponds
to an incompletely substituted species in which some amino end
groups of 3 a do not react with the N,P,Cl, moieties. This assumption is supported by the fact that final products 3b are not
fully soluble in organic solvents (as any compound of any generation of type b should be); a small amount (less than 10% in
weight) is insoluble in organic solvents but soluble in water (like
any precursor of type a).
In other words, at the level of third-generation dendrimers 3 b,
about 10% excess N,P,CI, rather than the strict 1 :30 stoichiometry is required to obtain the compounds quantitatively.
Nevertheless, further precursors and generations of dendrimers
from sexapus cores may be synthesized till the fifth generation,
but the amount of impurities (that is, species not completely
substituted) increases slowly but steadily with the size of molecules. An efficient approach for circumventing this difficulty is
based on the following consideration : the three steps consisting
of the successive graft of n linkers, n N,P,CI, fans, and another
5n linkers are strictly identical to the graft of n sexapus molecules! In Scheme 2, compounds 5a, which are precursors of Sb,
were synthesized from compounds 3 b in this way. Such a procedure sharply decreases the risk of generating impurities.
In our opinion, cyclophosphazene dendrimers are Unusual
Fascinating Objects (UFOs!) built from “fractal” structures
(Scheme 3) where the chaining (one diamino tentacle plus one
N3P,C1, fan) can be repeated ad libitum. The upper limit to
these constructions will be given by mathematics[’21 or chemistry or both.
The structures of compounds 1 b, 2a, 2 b, and 3 a were calculated with the molecular modeling package
on an IBM
RISC 6000 station. The units H,N(CH,),NH, and H,N(CH,),NHN,P,Cl,
were constructed and their structures
minimized; in the conformational analysis a tree-searching al-
’.
580
0 VCH
Verlugsgesellschufi mbH. 0-69451 Weinheim, 1995
NH
Scheme 3 . The ”fractal” structure of the third-generation dendrimers.
g ~ r i t h m [ ’with
~ ] an extended MM2 force field[’sJand a NewtonRaphson minimizer was used. The force field was tuned with
results from X-ray structure and electron diffraction analyses.
Five iterations were then used to build the full molecule in which
steric contacts are avoided (Fig. 1). Careful checking of these
structures shows that the limitation of the growth of the dendrimers within the cyclophosphazene series will be more probably due to the progressive filling of the “holes” around the
primitive core than to a saturation of peripheral sites as predicted by de Gennes.[”] It seems to us that this important point will
have to be given more weight than the “external saturation of
active sites on the periphery of the dendrimer” in the design of
future dendrimers. Most recently we succeeded in purifying
fourth and fifth generations by single S O , column chromatography with n-hexaneldiethyl ether (2/1) as the eluent and are
attempting to obtain crystals of these dendrimers.
Experimental Procedure
The ” P NMR spectra were recorded on a Bruker AC 200 Spectrometer with H,PO,
(85%) as external reference. DCI and FAB mass spectra were recorded o n a Ribermag R1010-H Quadrupole Mass Spectrometer. Hexachlorocyclotriphosphazene
(degree of purity r99.X%) was generously donated by Shin Nisso Kako Co. Fluka
supplied us with the primary diamines (degree of purity 2 9 8 % ) .
Alumina-supported potassium hydroxide: Potassium hydroxide (Prolabo Rectapur, l l g) in H,O (250 mL) was mixed with neutral alumina for chromatography
(Fluka, type 207 C , 90-1 10 mesh, 50 g). After stirring for 5 min, the water was
removed under reduced pressure. The resulting powder was further dried at 70°C
for 24 h in an oven. This reagent [termed ALPOT(50: 1l)] may be kept in a desiccator without loss of activity for several months.
Synthesis of l a : ALPOT(50:ll) (150 g) was first impregnated with a solution of
N,P,CI, in toluene (1 1.96 g in 400 mL) and the solvent was immediately removed
in vacuo at 25 “C to fix N,P,CI, to the alumina surface. Second, this system was
impregnated with a solution of the 1.6-diaminohexane (6 equiv. 24.16 g) in toluene
(200 mL), and the solvent was immediately removed in vacuo as before. Washing of
the solid support twice with 200 mL portions of toluene gave La, n = 6 (15.75 g.
55.5%). ” P NMR (X1.01SMHz): 6 =1X.3 (s); DCI/NH, MS: m / s : 826 (MH’).
710 ( M t - HN(CH,),NH,), 594 (M’ - 2(HN(CH2),NH2)): FAB-MS (glycerol!
thioglycerol (XOj20) as matrix): m / i 826, 710, 594, 498 ( M + - 3(HN(CH,),NH,)).
Thus. aminolysis of N,P,CI, by 1,6-diaminohexane on ALPOT(50: 11) yields instantaneously the pure hexadangling (or hexapodane) sexapus 1 a, n = 6 as a hygroscopic microcrystalline white powder (m.p. 39 ” C ) . Moreover, the persubstitution of
the 6 CI atoms of N,P,CI, by tentacles is accompanied by a vanishing of both strong
0570-0833~95jOS0S-OSSO$10.00+ ,2510
Angen,. Chem. Int. Ed. Engl. 1995.34, No. 5
COMMUNICATIONS
vibrational bands v,(PCI) and v,,(PCI) of N,P,Cl, at 600 ;ind 520cm
emergence of v(NH) bands at 3382 and 3319 cm- I .
and the
Synthesis of I b, n = 6: The reaction (a) w a s performed in Et,O with Et,N as HCI
scavenger. The reaction wab considered complete after 4X h when the singlet of 1 a.
n = 6 in the "P N M R spectrum had disappeared. The product was soluble in
CDCI,. 3 1 PN M R (81.015 MHz): A,B system (G(PCll\iH) =18.7 (1). K(PC1,) =
21.3 (d. 'J(P,P) = 46.6 Hz), h(P.core) = 22.0 (s). FAB-MS (meto-nitrohenzyl octyl
ether (MNBE) as matrix): n i k : 2693 ( M * ) .We had to use MNBE instead of the
more common glycerolithioglycerol mixture as the matrix. because thc 30 chlorine
atoms of 1 b, n = 6 are substituted in situ by glyceryl and thioglyceryl groups. which
led to molecules with masses much larger than 2000. beyond the thrcshold of response of the detector. The 1R spectrum reveals an emergence of one v(NH) band
and no PCI band in the 400 -600 c m - ' range.
at 32.34cm
Compounds 2a/2b, 3a/3b, 4a/4b, and Sa/Sb with n = 6 were synthesized
analogously to l a and 1 b, under the respective stoichiometric conditions. Average
yields: l a -1b 90%. I b - 2 a 67%, Z a + 2 b 75%. 2 b + 3 a 77%. 3a - 3 b 805'0,
3 b - 4 a 65%. 4 a - 4 b 92%. 4 b + Sa 69%, and Sa Sb X0%. The overall yield
for the target molecule 5b was thus 9 % . However. in terms of molecular weights.
1 g of l a yields 199g ofSb.
Microanalytical data are not reported here, because the huge variation5 with respect
to the carbon and chlorine content from one step to the next makes identification
of each step unambiguous [6]
Received : October 10. I994 [Z 7387 IE]
German version. Angeri. C'hrm. 1995. 107. 610
Keywords: dendrimers . phosphorus compounds
~~
[l] Reviews: D. A. Tomalia. A. M. Naylor. W. A. Goddiird 111, A n g c w CIiem.
1990./02,119: A n , p r . Chen7. lnl. Ed Engl. 1990, ZY. 138; H. B. Mekelburger.
W. Jaworek. F. Vogtle. ibid. 1992. 104. 1609 and 1992, 3 / . 1571: M F. Ottaviani. S. Bossmann, N . J. Turro. D. A. Tomalia, J A m C/uw/.Sor. 1994.116.661,
and references therein.
[2) H . Uchida, Y. Kabe, K. Yoshino, A. Kawamata. T. Tsumuraya. S. Masamune,
J. Am. Chem. Soc. 1990. 112. 7077; L. J. Mathias, T. W Carothers. &id. 1991.
/ / 3 , 4043, E. A. Rebrov. A. M . Muzafarov, V. S. Pdpkov. A. A. Zhdanov.
Dokl. Ak-cid. Nauk SSSR 1989,309,376; A. W. van der Made, P. W. N. M. van
Leeuwen. J. Ci7t-m. So<. Cliem. Commun. 1993, 1400: D. Seyferth, D. Y Son,
A. L. Rheingold, R. L. Ostrander, Organomc,tallic.! 1994. 13. 2682.
[3] P. Marerolles, V. Huc. unpublished results.
[4] K . Rengan. R. Engel. J. Chem. Soc. Cliem. Commun. 1990. 1084; J C'hem. Sor.
Perkin Trans. 11991,987; R. Engel, K . Rengan. C . S. Chan, PliorphorusSuifur
Silicon Relut. Elem. 1993, 77, 221.
[ 5 ] N. Launay, A ,- M . Caminade, R. Lahana, J.-P. Majoral. A n ~ r w Chrm.
.
1994,
106, 1682; AngeM. Chem. Inl. Ed. Engi. 1994. 33, 1.589.
[6] F. Sournies, L. Labrousse, M. Graffeuil, F. Crasnier, J.-P. Faucher. M.-C.
Labarre, J.-F. Labarre, Phosphorus S u f u r Silicon Relar. Hem. 1994. 89. 47.
[7] F. Sournies, C. Fouga. M Graffeuil. J.-P. Faucher, F. Crdsnier, M.-C. Labarre.
J.-F. Labarre, Phosphorus Sullirr Silicon Relar. Elem. 1994, 90. 159.
[S] N Launay, A.-M. Caminade, JLP. Majoral. J. Am C h m Soc., in press.
[9] F. Sournies, M. Graffeuil, B. Segues, F. Crasnier, D. Semenzin, G. EtemadMoghadam, M. Koenig. J.-F. Labarre, Phosphorus Sulfur Silicon Reiut. Elem.
1994, 86. I ; B. Segues, F Sournies. F. Crasnier, J.-F Labarre. ihrrl. 1994, 88,
[lo] J. M. J. Frechet, Science 1994. 263, 1710.
Ill] Bino represents a unit comprising two NzP, rings and one diamino bridge: G.
Guerch. L F . Labarre. R. Lahana. R. Roques, F. Sournies. J Mol. Struct. 1983,
9Y, 275; P. Castera, J.-P. Faucher. M. Granier, J.-F. Labarre. P/io.sphoru.s Suifirr
Relar. Elem. 1987. 32. 31.
1121 P. G. de Gennes. H. Hervet. J Phj..s. Left. 1983, 44. L 351
[I31 The program M A D is available from Oxford Molecular Ltd., Oxford Science
Park. The Magdalen Centre. GB-Sandford on Thames. OX44GA Oxford
(UK).
[14] M. Lipton, C . Still, J. Compul. Chem. 1988. 9. 343.
[I51 N. L. Allinger, Y H. Yuh, J.-H. Lii, J. Am. Cl7em. Soc. 1989. / / / , 8551.
Fig. 1. From top to bottom: Structures of dendrimers Ib, Za, 2b. and 3 a from
moleculiir inodeling \tudies
Документ
Категория
Без категории
Просмотров
3
Размер файла
1 095 Кб
Теги
cyclophosphazenes, generation, fifty, dendrimer, spherical
1/--страниц
Пожаловаться на содержимое документа