Synthesis, thermal properties and X-ray structural study of weak CHOLC hydrogen bonding in aliphatic polyester dendrimers

Jarmo Ropponen, Kalle Nattinen, Manu Lahtinen and Kari Rissanen*

Nanoscience Center, Department of Chemistry, University of Jyvaskyla, P.O.B. 35 FIN-40014, University of Jyvaskyla, Finland. E-mail: Kari.Rissanen@jyu.; Fax: 1358 14 2602501; Tel: 1358 14 2602672 Received 9th September 2004, Accepted 12th October 2004 First published as an Advance Article on the web 22nd October 2004

Paper

Dendritic polyester compounds based on polyol with three, four and six reactive hydroxy groups as a molecular core, chloroacetyl chloride (or bromoacetyl bromide) and sodium metal enolate were prepared by a simple two-step synthetic procedure. The compounds were characterised by using the NMR and MS techniques, and the thermal properties were measured by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The structures of the crystalline compounds were determined by X-ray single crystal diffraction. Detailed analysis of the structures showed that the self-complementarity of the molecules together with a multitude of weak CHOLC hydrogen bonding results in crystalline dodecamethyl and dodecaethyl esters 9a and 9b, whereas slight modication in the structure of nonaethyl ester 8 renders it viscous oil.

Introduction
The eld of dendrimer chemistry is currently a subject of intense attention because dendrimers are chemically discrete, highly branched polymer-like macromolecules, which have a well-dened 3-D structure.1 These characteristics of dendrimers contain many unique properties, such as viscosity2 and thermal behaviour,3 which differ signicantly from those of linear polymers. Due to the wide variety of their properties, dendrimers can be used in applications like light harvesting systems,4 catalysis,5 molecular encapsulation6 and biomedical applications.7 In general, there are two different synthetic concepts to construct dendrimers. In the divergent8 approach the ABx monomer is added layer by layer around the core molecule. In the convergent9 method the branched parts, so-called dendrons are synthesized from ABx monomer, and in a nal step these parts are joined into the core molecule to form a dendrimer of desired generation. There is a huge variety of potential use of dendritic structures, and the wide range of applications is being explored with dendrimers and dendrons. In fact, it becomes evident that dendrimer chemistry is branching out to two different directions which are biological and materials chemistry.10 Many future applications of dendritic systems will be developed for the eld of biomaterials where the purity and functionality of the material are one of the key issues. Our interest lies in aliphatic polyesters due to their use as new organic biocompatible materials for dental and bre applications. In this paper we describe a two-step synthesis, structural characterization and thermal behaviour of dendritic aliphatic polyesters. The desired dendrimers are based on the use of chloroacetyl chloride (or bromoacetyl bromide) as the connector moiety between the core polyol (three, four and six reactive hydroxy groups) and a sodium enolate. To our surprise, the intermediate polyhalide compounds were crystalline solids with relatively high melting points, and secondly, the single crystals of the dodecamethyl and dodecaethyl ester dendrimers could be obtained. No X-ray structures of dendritic polyesters of this kind have been presented before. The single crystalline compounds enabled us to survey the intermolecular interactions of these compounds.11 According to recent principles in crystal engineering, the crystal formation does DOI: 10.1039/b413799j

not necessarily require strong interactions, but the abundant weak interactions are sufcient enough, provided that the structural self-complementarity supports this.11 Functional self-complementarity requires the presence of both parts of the supramolecular synthon12 within one molecule. The study of these interactions is essential for understanding the physical properties of the compounds (such as melting point and viscosity) and thereby for the development of crystal engineering techniques.13

Results and discussion

The title aliphatic polyester dendrimers were synthesized using a simple two-step procedure. The synthetic route for these compounds is shown in Schemes 1 and 2. The starting polyol, 1,1,1-Tris(hydroxymethyl)ethane 1, pentaerythritol 2 or dipentaerythritol 3 was reuxed with chloroacetyl chloride/bromide 4a/4b until the formation of gaseous HCl ceased. The resulting polychlorides/bromides were puried by column chromatography (silica gel, eluting with 6 : 4 hexaneethyl acetate) and/ or recrystallization from ethanol. The pure white crystalline polychlorides 5, 6a, 6b and 7 were obtained in 72, 83, 86 and 71% yields, respectively. In the second step, the esters 810 (Scheme 2) were prepared by using the reaction of Newkome et al.14 by reacting the polychloride with NaC(CO2R) [R ~ Me or Et] in DMF at 90 uC for 20 h. The mixture was cooled down, DMF was evaporated and CHCl3 (75 ml) was added to the solution. Finally, the solution was washed with water (3 6 30 ml), saturated NaHCO3 (3 6 30 ml), water (3 6 30 ml) and was dried on anhydrous MgSO4. Purication was made by column chromatography (silica gel, eluting 1 : 1 hexaneethyl acetate) obtaining 8 (73% yield) as a viscous liquid. Compounds 9a and 9b were prepared by the same procedure. The polyesters were crystallized as pure white solids without column chromatography, purication gave 9a and 9b in 93 and 79% yields, respectively. Unfortunately, compound 10 could not be obtained in pure form but a mixture of partially reacted products was obtained, even if longer reaction times were used. CrystEngComm, 2004, 6(91), 559566 559

This journal is # The Royal Society of Chemistry 2004

Scheme 1

The reason for the uncompleted substitution may be the steric hindrance of the two adjacent substitution sites. 1 H NMR spectra of the all polyhalides were quite straightforward and almost identical; a- and b-methylene protons gave singlet to ca. 4.2 and 4.1 ppm. For 6b, the peak shifts were 4.3 and 3.9 ppm, respectively. The hexachloride 7 gave three methylene singlets up to 4.4, 4.2 and 3.4 ppm. The b-methylene protons of 8 and 9b shifts upeld to 3.1 ppm and a triplet (d 1.3, J ~ 7.1 Hz) and a quartet (d 4.3, J ~ 7.1 Hz) for the ester methyl and methylene, respectively. Methylester 9a gave methyl singlet to 3.82 ppm. Furthermore, the 13C NMR spectra conrmed the suggested structures as all esters have four characteristic peaks: ca. d 37 for COCH2C; ca. d 63 CqCO; ca. d 166 COOR and ca. d 169 for OCOCH2. Molecular weight data were determined by ESI-TOF MS and their values agreed well with the calculated molecular weights. The thermal analyses of the compounds 57, 9a and 9b were carried out by differential scanning calorimetry (DSC) and by thermogravimetric/differential thermal analysis (TG/DTA), and the results are collected in Table 1. Some DSC curves from the rst and second heating scans are presented in Fig. 1. In case of the DSC measurements, the weights of the sealed sample pans (capillary holes) were controlled at the end of the heatingcooling cycles, showing only negligible weight changes in each case. On the rst heating scan, the polyhalides 57 exhibited only a single endothermic transition peak, which indicated the melting of the crystalline phase. Somewhat more complicated thermal transitions (subsequent melting crystallization events) were observed on polyesters 9a and 9b prior to the nal melting transition. The melting points (T m) of the polyhalides were inuenced by the number of the polyester branches and the type of the terminal groups. Compound 5 showed the lowest melting point (46.2 uC) of the chloride terminated compounds whereas compounds 6a and 7 with either four or six polyester branches exhibited clearly higher melting points at 98 and 95.2 uC, respectively. The higher melting points of 6a and 7 are most likely originating to some extent from the packing modes of the tetrahedral 560 CrystEngComm, 2004, 6(91), 559566

Scheme 2

and planar conformations (improved hydrogen bond ordering) which are tighter than those compared to compound 5 with only three asymmetrically emanating polyester branches, as can be seen in Fig. 2. Compound 6b (bromide terminated) deviated slightly from the rest of the polyhalides, as the observed T m (38.2 uC) on the rst heating scan was lower than would have been expected, since 6a and 6b are isomorphous structures. The low T m may partially be affected by the fact that DSC studies of 6b had to be carried out with slightly moisturized samples, as the compound proved to be hygroscopic. As mentioned earlier, the rst heating scans of the polyesters 9a and 9b showed multiple overlapping transitions before nal melting transition. More detailed DSC measurements (see Experimental section) showed that both polyesters experienced melting of the low temperature phase, which crystallized almost simultaneously to the high temperature phase, and nally this new polymorph melted at slightly higher temperature. For 9b, the sharp subsequent melting crystallizationmelting transitions occurred within a temperature range of 10 uC and were partially separated with heating rate of 2 uC min21 but with a rate of 100 uC min21 only a single melting transition was observed at 104 uC. In the case of 9a, the transitions were more severely overlapped despite the temperature range of the clustered peaks being broader, ranging from 110145 uC. The transitions could not separate even by using the slow heating rate, suggesting an occurrence of several coexisting meltingcrystallization and/or solid/solid phase transition events prior to the nal melting. On the rst cooling scan, only the glass transitions (T g) were observed for all compounds indicating that crystallization of the polyhalides 57 and the polyesters 9a and 9b from a melt is not induced at

Table 1 Thermal transition temperatures, corresponding enthalpies and thermal decomposition ranges for compounds 5, 6a, 6b, 7, 9a and 9ba Thermal transitions and enthalpy changes 1st heating run Comp. 5 6a 6b 7 9a 9b Mw 349.60 442.08 619.88 713.18 1056.85 1225.18 Trans. kAi [k A i] kAi kAi kAi kAi kAi iAk kAi uC (kJ/mol) 46.2 (32.5) [62.1 (0.9)]b 98.0 (33.2) 32.8 (12.2)c 95.2 (59.9) 109.9145.4 (57.2)d 101.3 (31.7) 103.9 (22.9)e 110.5 (42.0) 2nd heating run Trans. gAe gAe eAk kAi gAe gAe eAk kAi gAe gAe uC (kJ/mol) 242.1 222.7 16.2 54.4 233.1 214.6 37.4 89.7 23.4 215.4 Tg Tg (223.8) (29.6) Tg Tg (244.2) (51.9) Tg Tg Decomp. range/uC 274376 320554 309536 347600 316606 320626

a k ~ crystalline solid, i ~ isotropic liquid, T g ~ glass transition temperature taken from the half-step temperature of DCp extrapolated, g ~ glassy solid, e ~ elastic (rubbery). b Weak melting peak of the second polymorph (see text). c Sample moisturized during preparation as compound was hygroscopic. d Peak cluster including multiple peaks between 110160 uC, in which onset of the last almost isolated peak is presented. e The observed enthalpy changes for both polymorphs are partially affected by the almost coexisting crystallisation and melting events.

least with a given cooling rate; and in fact these compounds crystallized in most cases from a solvent or after prolonged storage at room temperature. On the second heating scans, T g values varied from 242.1 uC (5) to 23.4 uC (9a), being similar to those observed on the rst cooling. Furthermore, compounds 6a and 7 exhibited cold crystallization at temperatures about 40 uC above their glass transition temperatures (16.2 and 37.4 uC, respectively) as all the other compounds manifested only T g on the second heating scan. In the case of 7, the structural conformation of the crystallized phase was analogous to the original RT-phase since nearly the same T m was obtained. With compound 6a a new polymorph was formed which melted already at 54.4 uC whereas the original phase melted at 98 uC. With closer examination, the weak melting transition (62.1 uC, 0.9 kJ mol21) of this second polymorph of 6a was already seen on the rst heating scan, suggesting that small amount of the second polymorph was crystallized with the main phase. The thermal decomposition studies showed that the polyhalides 57 and the polyesters 9a and 9b started to decompose

mainly within 270350 uC and decomposed completely within 550630 uC, except for 5 which decomposed already below 400 uC. Slightly narrower decomposition temperature ranges were observed for polyhalides, as can be seen in Table 1. The polyhalides 5, 6a and 6b decomposed in a single stage, whereas compound 7 together with polyesters 9a and 9b decomposed in two stages. In the case of the two-stage decomposition, major weight loss ended around 400430 uC, after which the samples reached the zero weights with slower mass loss rate. It is assumed that on rst stage the polyester backbone started to break down, following with partial carbonization before the nal oxidation of the carbon-based materials at higher temperatures.

Fig. 1 DSC curves of the compounds 5, 6a, 6b, 9a and 9b from the rst (black lines) and second (red lines) heating scans. The peak cluster of compound 9a is seen only partially, as the scans are cut to 120 uC for clarity.

Fig. 2 A plot with thermal ellipsoids shown at 50% probability level for 5 (top left), 6a (top right), and 7 (bottom) with atomic labels. The structures of 6a and 6b are isomorphous, therefore only 6a is presented.

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Table 2 Crystallographic parameters for compounds 57 Compound Empirical formula Formula wt. Crystal color, shape Crystal dimensions/mm Crystal system Space group a/A b/A c/A a/u b/u c/u V/A3 Dc/Mg m23 Temperature of collection/K Z Robs Rall GooF h range for data collection/u Scan type Re. collected/unique/cell renement Rened parameters Res. electron density e A23 5 C11 H15 Cl3 O6 349.58 Colorless, blocks 0.30 6 0.30 6 0.30 Orthorhombic Pbca No. 61 9.8372(2) 17.5742(3) 17.8119(4) 90 90 90 3079.34(11) 1.508 173(2) 8 R1 ~ 0.0314, wR2 ~ 0.0668 R1 ~ 0.0490, wR2 ~ 0.0728 1.025 3.09 to 25.68 2u, w/v 5455/2908/3303 181 0.234/20.246 6a C13 H16 Cl4 O8 442.06 Colorless, blocks 0.80 6 0.40 6 0.20 Orthorhombic Pbca No.61 a ~ 10.5218(2) b ~ 18.4159(5) c ~ 19.3598(7) 90 90 90 3751.3(2) 1.565 173(2) 8 R1 ~ 0.0484, wR2 ~ 0.1154 R1 ~ 0.0705, wR2 ~ 0.1267 1.042 3.05 to 25.00 2u, w/v 6185/3294/3624 226 0.433/20.459 6b C13 H16 Br4 O8 619.90 Colorless, blocks 0.80 6 0.80 6 0.60 Orthorhombic Pbca No.61 10.8238(2) 18.6966(3) 19.5622(3) 90 90 90 3958.77(11) 2.080 173(2) 8 R1 ~ 0.0563, wR2 ~ 0.1332 R1 ~ 0.0735, wR2 ~ 0.1454 1.058 3.55 to 25.02 1u, w/v 22957/3480/3819 226 1.214/21.144 7 C22 H28 Cl6 O13 713.14 Colorless, blocks 0.08 6 0.05 6 0.05 Monoclinic P21/c No.14 14.4132(2) 17.6761(3) 24.2819(3) 90 92.404(8) 90 6180.8(2) 1.533 173(2) 8 R1 ~ 0.0558, wR2 ~ 0.1249 R1 ~ 0.0931, wR2 ~ 0.1463 1.014 3.05 to 25.02 1u, w/v 18575/10824/10826 739 0.894/20.633

The single crystals for 5, 6a, 6b, 7, 9a and 9b were obtained from ethanol. The crystal structures for the compounds 5, 6a, 6b, 7,9a and 9b were determined by X-ray single diffraction and the crystal data are presented in Tables 2 and 3. The molecular structures of the polyhalides 57 are shown in Fig. 2 and they do not show any abnormal bond distances or angles. Besides the CHOLC interactions, there are altogether ve different hydrogenhalide interactions. Their strength and number are, however, negligible compared to those of the abundant CHOLC interactions.{ Compounds 57 have three different modes of packing which originate from the number and conformation of their
{ CCDC reference numbers 249806249811. See http://www.rsc.org/ suppdata/ce/b4/b413799j/ for crystallographic data in CIF or other electronic format. Table 3 Crystallographic parameters for compounds 9a and 9b Compound Empirical formula Formula wt. Crystal color, shape Crystal dimensions/mm Crystal system Space group a/A b/A c/A a/u b/u c/u V/A3 Dc/Mg m23) Temperature of collection/K Z Robs Rall GooF h range for data collection/u Scan type Re collected/unique/cell renement Rened parameters Res. electron density/e A23 9a

branches. With tetrahedral orientation of branches such as that of 6a and 6b (which have isomorphous structures), the molecules form a tight, intertwined network. The lattice structure is held together by weak hydrogen bonds between methylene hydrogens and carbonyl oxygens. Four-branched structures with a exible core tend to adopt either tetrahedral or planar conformation.15 Fig. 3 presents the weak intermolecular hydrogen bonds for compounds 5, 6a and 7. With only three full-size branches, compound 5 is not able to adopt neither planar nor tetrahedral structure. Compound 7 with six arms forms planes of molecules with CHOLC interactions between individual molecules. The packing is similar to that observed earlier with pyridinecarboxylic acid functionalized dendritic molecules.15 The molecular structures of the polyesters 9a and 9b are shown in Fig. 4. The structure 9b contains disorder in the

9b C54 H76 O32 1237.15 Colorless, prisms 0.40 6 0.40 6 0.20 Monoclinic C2/c No. 15 26.0330(5) 13.3140(3) 19.6140(4) 90 114.771(2) 90 6172.8(2) 1.331 173(2) 4 R1 ~ 0.0982, wR2 ~ 0.2744 R1 ~ 0.1380, wR2 ~ 0.3108 1.033 3.0025.03 2u, w/v 10131/5449/5590 488 0.809/20.524

C41 H52 O32 1056.83 Colorless, needles 0.70 6 0.30 6 0.20 Tetragonal I4 No. 82 18.3908(4) 18.3908(4) 7.2728(2) 90 90 90 2459.8(1) 1.427 173(2) 2 R1 ~ 0.0737, wR2 ~ 0.2063 R1 ~ 0.0804, wR2 ~ 0.2141 1.060 3.0125.67 1u, w/v 7583/2306/4076 165 0.418/20.178

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Fig. 4 A plot with thermal ellipsoids shown at 50% probability level for 9a (a) and 9b (b). The non-hydrogen atoms of the asymmetric unit are numbered. The disorder at the periphery is removed.

Fig. 3 The weak hydrogen bonds between molecules of 5 (a), 6a (b) and 7 (c) presented as dashed lines. Click here to access a 3D image of Fig. 3a. Click here to access a 3D image of Fig. 3b.

intermolecular H-bonding in 6a/b and 9a/b, the overall packing is surprisingly similar and can be schematically presented as an interlocked row (Fig. 6). The analysis of the weak intermolecular hydrogen bonds (being predominantly to the carbonyl oxygens) reveals no unusual bond lengths or angles. The minimum, maximum and

periphery of the molecule. The independent arms in the asymmetric unit (excluding one) were split to two separate orientations (per arm) starting from the carbonyl carbon and the populations for these were allowed to rene freely after which they were xed to enable the renement of the temperature factors. All but one of the six (and the single solvent atom) were rened anisotropically. Both esters have their four branches tetrahedrally orientated. Both structures show a very tight, intertwined packing with a number of weak hydrogen bonds between the branches, surprisingly with no EtOH solvent molecules. As in 6a and 6b, the hydrogen bonds are formed between the methylene hydrogens and the carbonyl oxygens. The packing of 9a and 9b is presented in Fig. 5. Although the halides 6a and 6b and the polyesters 9a and 9b all have tetrahedral orientation of their branches, their packing patterns differs signicantly. The relatively small diameter of the branches of 6a and 6b results in close encounters of the branches of several adjacent molecules and thereby forming a tightly packed structure. As the length of the branches grows along with the growth of the dendrimer, the complexity of intertwining is reduced. In 9a and 9b, the branches of one molecule are tightly intertwined with only two adjacent molecules within one row (see Fig. 6). Despite the differences in the

Fig. 5 Top: space-lling presentation of the intertwined packing of three molecules of 9a (left) and 9b (right), and bottom: four neighbouring rows of molecules seen along the crystallographic c-axis (9a, left) and b-axis (9b, right). Click here to access a 3D image of compound 9a. Click here to access a 3D image of compound 9b.

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of the terminal groups, chloride ended compounds having higher T m than the bromide ended; the highest T m being 98 uC for the compound 6a with four chloride-end groups and only slightly lower T m was obtained for compound 7 with six chlorides. The melting points of the polyesters with aliphatic end groups (methyl or ethyl) decreased from 145 to 110 uC as the methyl groups were changed to the ethyl groups. Finally, after the rst heating only the glass transition temperatures were observed for all compounds, except for 6a and 7, on subsequent scans indicating the low crystallizability of the compounds from a melt. The recrystallization of the polyhalides 6a and 7 was more favoured, as cold crystallization and subsequent melting transitions were observed in both compounds above their glass transition temperatures. Compounds 5, 6a, 6b, 7, 9a and 9b were crystalline and their crystal structures were determined. In general, the tetrahedral orientation of the dendritic branches and a multitude of weak CHO intermolecular hydrogen bonds together with steric and functional self-complementarity will result in a tight intertwined packing of the molecules. The result of this packing is the crystallinity of the compounds 9a and 9b. With only three full-size branches, compound 8 failed the requirements of self-complementarity and was rendered a viscous oil.

Experimental
All chemicals were purchased from major chemical suppliers as highest purity grade and used without any further purication. Column chromatography was performed with Merck silica gel 60 F254, particle size 0.0400.063 mm, using hexaneethyl acetate mixtures. All 1H and 13C NMR experiments were performed in 0.020.05 M CDCl3 solutions with a Bruker Avance DRX 500 NMR spectrometer working at 500.13 MHz for 1H, and 125.77 MHz for 13C experiments, unless otherwise mentioned. The 1H and 13C NMR chemical shifts were referenced to the residual signal of partly deuteriated solvent: d(C1HCl3) ~ 7.26 ppm from the internal TMS and to the signal of solvent d(13CDCl3) ~ 77.00 ppm from the internal TMS, respectively. Electrospray mass spectrometric measurements were obtained using an LCT time of ight (TOF) mass spectrometer with electrospray ionisation (ESI, Micromass LCT). For the accurate mass measurements, the calibration of the instrument was made with NaI. Leucine encefal were used as the reference ions for compounds 5 and 6a and substance p for compounds 710, respectively. The single-crystal X-ray diffraction was carried out with a Nonius KappaCCD diffractometer with graphite monochromatized Mo Ka (l ~ 0.71073 A) radiation. COLLECT software was used in the measurement and DENZO-SMN16 for processing the data. The structures were solved and rened by full-matrix leastsquares on F2 with WinGX-software package utilizing SHELXS97 and SHELXL97 modules.1719 Hydrogen atoms were rened by a riding model. Empirical absorption correction was performed for 6b. The graphic presentations of the structures were created with the software Diamond.20 DSC measurements were done with PerkinElmer PYRIS Diamond DSC using 50 ml (sealed) aluminum sample pans with capillary holes. The temperature calibration was made by three standard materials (n-decane, In, Zn) and the energy calibration by indium standard. For the nal results, the samples were heated and cooled twice at a rate of 10 uC min21 in the temperature range of 240 uC to ca. 30 uC over the pre-determined (preliminary DSC measurements) isotropization temperature of each compound. In addition, more detailed DSC measurements were carried out for compounds 9a and 9b to separate the overlapping transitions or to prevent the formation of the mesophases by heating the samples either very slowly or rapidly with rates of 2 uC min21 or 100 uC min21, respectively. The sample weights used in the measurements were about 46 mg.

Fig. 6 The intertwining via intermolecular interactions of molecules of 6a, 6b (a), 9a (b) and 9b (c), and its schematic presentation (d). Click here to access a 3D image of Fig. 6c.

average values for the distances d(HA), D(DA), and angle (DHA) are presented in Table 4. The minimun angle and maximum distances d and D are a de facto result of used cutoff distances and angles. Interestingly, compound 7 had the largest amount of weak, intermolecular hydrogen bonds (20), while, e.g. compounds 9a and 9b have 4 and 8 bonds, respectively.

Conclusions
Dendritic aliphatic polyesters were synthesized by a simple two-step synthetic procedure in high yields. The thermal analyses of the compounds showed that the melting points of the polyhalides were dependent on the branching and the type
Table 4 The minimum, maximum, and average of the distances d(HA), D(DA), and angle (DHA) of the weak hydrogen bonds in compounds 5, 6a, 6b, 7, 9a and 9b Minimum d(HA)/A D(DA)/A Angle (DHA)/u 2.180 2.705 100.4 Maximum 2.950 3.779 167.8 Average 2.478 3.258 132.5

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Transition temperatures are taken from the peak onsets. The thermal decomposition paths for the dendritic polyesters were obtained with Perkin Elmer Diamond TG/DTA. Measurements were done by using platinum pans under synthetic air atmosphere (ow rate of 110 ml min21) at a temperature range of 25700 uC (heating rate of 20 uC min21). The temperature calibration of TG/DTA equipment was carried out by using melting points of ve reference materials (In, Sn, Zn, Al, Au) and the energy calibration was made with indium standard. The weight balance was calibrated by measuring the standard weight as a function of temperature. The sample weights used in the measurements were about 57 mg. Tris-(2-chloro-acetoxymethyl)methane (5) 1,1,1-Tris(hydroxymethyl)ethane 1 (3.44 g, 28.60 mmol) was reuxed with chloroacetyl chloride 4a (26.36 g, 233.4 mmol) until gaseous HCl formation was ended. Excess of acid chloride was removed in vacuo, and the crude product was puried by column chromatography (SiO2) hexaneethyl acetate (1 : 1) to give viscous oil which crystallized after several days. Recrystallization from ethanol gave 5 7.24 g (72.4%) as a white solid. Rf ~ 0.72. 1H (CDCl3, 500 MHz) d 4.13 (s, 6H, CH2), 4.07 (s, 6H, CH2), 1.06 (s, 3H, CH3). 13C (CDCl3, 126 MHz) d 166.9, 66.9, 42.6, 40.5, 16.8. ESI-TOF1: m/z calcd. for C11H15Cl3O6Na; [M 1 Na]1 ~ 370.9832; found 370.9900 [M 1 Na]1. Anal. Calcd. for C11H15Cl3O6 6 H2O: C, 36.84; H, 4.50. Found: C, 37.04; H, 4.35. Tetrakis-(2-chloro-acetoxymethyl)methane (6a) Pentaerythritol 2 (3.08 g, 22.6 mmol) was reuxed with chloroacetyl chloride 4a (15.3 g, 136 mmol) for 45 min. The excess of 4a was removed in vacuo. The residue solidied on cooling and was recrystallized from ethanol to give white akes with a yield of 8.3 g (83%). 1H (CDCl3, 500 MHz) d 4.28 (s, 8H, CH2), 4.08 (s, 8H, CH2). 13C (CDCl3, 126 MHz) d 166.7, 63.3, 42.6, 40.5. ESI-TOF: m/z calcd. for C13H16Cl5O8 [M 1 Cl]2: 474.9288; found 474.9301 [M 1 Cl]2. Anal. Calcd. for C13H16Cl5O6?H2O: C, 34.62; H, 3.80. Found: C, 34.63; H, 3.63. Tetrakis-(2-bromo-acetoxymethyl)methane (6b) Pentaerythritol 2 (1.69 g, 12.4 mmol) was reuxed with bromoacetyl bromide 4b (12.50 g, 61.9 mmol) for 45 min. The excess of 4b was removed in vacuo. The residue solidied on cooling and was recrystallized from ethanol to give white akes with a yield of 6.6 g (86%). 1H (CDCl3, 250 MHz) d 4.29 (s, 8H, CH2), 3.86 (s, 8H, CH2). 13C (CDCl3, 63 MHz) d 166.7, 63.6, 43.0, 25.3. 2,2,2-tris-(2-chloro-acetoxymethyl)-ethoxymethyl-tris-(2chloro-acetoxymethyl)methane (7) Dipentaerythritol 3 (7.13 g, 28.0 mmol) was reuxed with chloroacetyl chloride 4a (25.5 g, 252 mmol) for 2 h. The excess of 4a was removed in vacuo. The residue solidied on cooling and it was recrystallized twice from ethanol to give white akes with a yield of 14.2 g (71%). 1H (CDCl3, 250 MHz) d 4.42 (s, 12H, CH2), 4.23 (s, 12H, CH2), 3.41 (s, 4H, CH2). 13C (CDCl3, 63 MHz) d 167.0, 70.9, 61.1, 45.7, 42.8. ESI-TOF2: m/z calcd. for C22H28Cl17O13 [M 1 Cl]2: 744.9350; found 744.9366 [M 1 Cl]2. Trikis-(2,2,2-tris-(methoxycarbonyl)-acetoxymethyl)methane (8) Trikis-(2-chloro-acetoxymethyl)methane 5 (0.60 g, 1.72 mmol) was added to a stirred solution 1.58 g (6.18 mmol) of NaC(CO2Et)3 in DMF (30 ml) at 90 uC. After 20 h, the solution was cooled down to RT, DMF was evaporated and CHCl3 (75 ml) was added. The solution was washed with water

(3 6 30 ml), saturated NaHCO3 (3 6 30 ml), water (3 6 30 ml), and dried over anhydrous MgSO4. The crude liquid product was puried by column chromatography (SiO2, hexaneethyl acetate, 1 : 1) to give 8 as a clear liquid with a yield of 1.18 g (73.3%). Rf ~ 0.54. 1H (CDCl3, 500 MHz) d 4.26 (q, J ~ 7.1 Hz, 18H, CH2), 4.03 (s, 6H, CH2), 3.13 (s, 6H, CH2), 1.27 (t, J ~ 7.1 Hz, 27H, CH3), 1.00 (s, 3H, CH3). 13C (CDCl3, 127 MHz) d 169.3, 165.9, 66.4, 63.4, 62.6, 38.2, 37.2, 16.8, 13.8. ESI-TOF1: m/z calcd. for C41H60O24Na; [M 1 Na]1 ~ 959.3372; found 959.3333 [M 1 Na]1. Tetrakis-(2,2,2-tris-(methoxycarbonyl)-acetoxymethyl)methane (9a) Tetrakis-(2-chloro-acetoxymethyl)methane 6 (1.27 g, 2.88 mmol) was added to a stirred solution 2.70 g (12.7 mmol) of NaC(CO2Me)3 in DMF (40 ml) at 90 uC. After 20 h, the solution was cooled down to RT and CHCl3 (75 ml) was added. The solution was washed with water (3 6 30 ml), saturated NaHCO3 (3 6 30 ml), water (3 6 30 ml), and dried over anhydrous MgSO4. The solution was concentrated in vacuo, and then ethanol was added. The product was crystallized as white akes. The yield of 9 was 2.8 g (93%). 1H (CDCl3, 250 MHz) d 4.08 (s, 8H), 3.73 (s, 36H), 3.09 (s, 8H). 13C (CDCl3, 63 MHz) d 168.9, 166.0, 62.9, 62.6, 53.5, 41.5, 37.06. ESI-TOF1: m/z calcd. for C41H52O32Na [M 1 Na]1: 1079.2339; found 1079.2330 [M 1 Na]1. Anal. Calcd. for C41H60O24 6 H2O: C, 45.82; H, 5.06. Found: C, 46.03; H, 5.02. Tetrakis-(2,2,2-tris-(ethoxycarbonyl)-acetoxymethyl)methane (9b) Tetrakis-(2-chloro-acetoxymethyl)methane 6 (1.44 g, 3.26 mmol) was added to a stirred solution 3.33 g (13.1 mmol) of NaC(CO2Et)3 in DMF (40 ml) at 90 uC. After 20 h, the solution was cooled down to RT and CHCl3 (75 ml) was added. The solution was washed with water (3 6 30 ml), saturated NaHCO3 (3 6 30 ml), water (3 6 30 ml), and dried over anhydrous MgSO4. The solution was concentrated in vacuo, and ethanol was added. The product crystallized as white akes with a yield of 3.13 g (79%). 1H (CDCl3, 500 MHz) d 4.27 (q, J ~ 7.1 Hz, 24H, CH2), 4.18 (s, 8H, CH2), 3.14 (s, 8H, CH2), 1.28 (t, J ~ 7.1 Hz, 36H, CH3). 13C (CDCl3, 126 MHz) d 169.0, 165.7, 63.3, 63.0, 62.4, 41.4, 36.9, 13.6. ESI-TOF1: m/z calcd. for C53H76O32Na [M 1 Na]1: 1247.4217; found 1247.4183 [M 1 Na]1. Anal. Calcd. for C53H76O32 6 H2O: C, 51.21; H, 6.32. Found: C, 51.43; H, 6.27.

Acknowledgements
We thank Spec. Lab. Tech Reijo Kauppinen for help in running the NMR spectra, Spec. Lab. Tech Mirja Lahtipera for running the ESI-TOF MS spectra, and docent Ilkka Pitkanen for helpful discussions concerning the interpretation of the DSC data. The National Technology Agency (TEKES, Project No. 40004/01) has supported this work nancially.

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