Scientific paper Crystal Structure and Thermodynamic Properties of N, N-dimethylnorephedrine Hydrochloride (C11H18NOCl) (s) You-Ying Di,a'* Yu-Xia Kong,a Wei-Wei Yang,a Da-Qi Wanga and Zhi-Cheng Tanb a College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province, P. R. China b Thermochemistry Laboratory, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China * Corresponding author: E-mail: yydi@lcu.edu.cn, diyouying@126.com, Tel: +86j-6j35-8538299, Fax: +86-635-8239121 Received: 04-11-2008 Abstract Crystal structure of N, N-dimethylnorephedrine hydrochloride (CjjHj8NOCl) (s) has been determined by an X-ray crystallography. The compound is orthorhombic P2j2j2j. Unit cell parameters are a = 7.2486(19) À, b = 9.674(3) À, c = 16.952(5) À; a= 90°, ß = 90°, 7= 90°, and Z = 4. Low-temperature heat capacities of the compound were measured by a precision automated adiabatic calorimeter over the temperature range from 80 to 390 K. A polynomial equation of heat capacities as a function of the temperature in the region of 80-390 K was fitted by least square method. Based on the fitted polynomial equation, the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated with 5 K step. In addition, DSC technique was used to determine the melting process of the compound. Keywords: N, N-dimethylnorephedrine hydrochloride; X-ray crystallography; adiabatic calorimetry; low-temperature heat capacity; thermodynamic function 1. Introduction N, N-dimethylnorephedrine hydrochloride (C11H18NOCl)(s) (CAS and EINECS registry numbers are 18760-80-0 and 242-557-4, respectively) is an important intermediate in medicine industry, which is often used to prepare a drug to treat the asthma.1 The asthma is a common disease especially for weaker and older people, which makes it necessary for manufacturing some efficacious medicines treating the illness. Heat capacity and standard molar enthalpy of formation of a substance are the most fundamental thermodynamic properties and closely related to other physical, biological, physiological and chemical properties.2,3 However, crystal structure and thermodynamic properties of the title compound have not been reported in the literature. These results are instructive and urgently needed in order to develop its new appli- cation fields, to improve the techniques of chemical synthesis in which it participates, and carry out relevant theoretical research.4 For these purposes, in the present work, crystal structure of the substance has been determined by an X-ray crystallography, low-temperature heat capacities were measured by a precision automated adiabatic calorimeter over the temperature range from 80 to 390 K, and the melting process was tested by DSC technique. 2. Experimental 2. 1. Sample The sample used in the measurements of X-ray crystallography and calorimetric experiments was commercially purchased from Neimenggu pharmaceutical factory (China). The content of the chloride in the compound was determined by chemical analysis. Elemental analyses (C, H and N) were carried out on a Vario EL III CHNOS instrument made in Germany. These results showed that purity of the sample was higher than 99.6%. A micro melting point device was used for measuring the melting point of the substance, and DSC technique was applied to measure the onset point, peak temperature, and enthalpy of melting process. 2. 2. X-ray Crystallography All diffraction data for the compound were collected on a Bruker Smart-1000 CCD area - detector diffractome-ter with graphite monochromated MoKa radiation (X = 0.71073) at 293(2) K using the program SMART and processed by SAINT-plus.5 Absorption corrections were applied by SADABS. The structure was solved by direct methods and refined with full-matrix least-squares technique using SHELXTL. All non-hydrogen atoms were refined anisotropically. All H-atoms were located theoretically and refined. The structural plots were drawn using the SHELXTL and OLEX programs. 2. 3. Adiabatic Calorimetry A fully automatic adiabatic calorimeter is used to measure heat capacities over the temperature range 78 < (T /K) < 400. The calorimeter is established in the Thermochemistry Laboratory in the College of Chemistry and Chemical Engineering, Liaocheng University, China. The principle and structure of the adiabatic calorimeter are described in detail elsewhere.6-8 Briefly, the calorimeter mainly comprised a sample cell, a platinum resistance thermometer, an electric heater, inner, middle and outer adiabatic shields, three sets of six-junction chromel-con-stantan thermopiles installed between the calorimetric cell and the inner shield, between the inner and middle shields, and between the middle and outer shields, respectively, and a high vacuum can. The miniature platinum resistance thermometer (IPRT No.2, produced by Shanghai Institute of Industrial Automatic Meters, 16 mm in length, 1.6 mm in diameter and a nominal resistance of 100 Q) is applied to measure the temperature of the sample. The thermometer is calibrated on the basis of ITS-90 by the Station of Low-Temperature Metrology and Measurements, Academia Sinica. The electrical energy introduced into the sample cell and the equilibrium temperature of the cell after the energy input are automatically recorded by use of a Data Acquisition / Switch Unit (Model 34970A, Agilent, USA), and processed on line by a computer. To verify the accuracy of the calorimeter, the heat capacities of the reference standard material (a-Al2O3) were measured over the temperature range 78 < (T /K) < 390. The sample mass used was 1.7143 g, which was equivalent to 0.0168 mol based on its molar mass, M(Al2O3) = 101.9613 g mol-1. Deviations of the experimental results from those of the smoothed curve lie within ± 0.2%, while the uncertainty is ± 0.3%, as compared with the values given by the former National Bureau of Standards9 over the whole temperature range. Heat-capacity measurements are continuously and automatically carried out by means of the standard method of intermittently heating the sample and alternately measuring the temperature. The heating rate and temperature increments are generally controlled at (0.1 to 0.4) K min-1 and (1 to 3) K. The heating duration is 10 min, and the temperature drift rates of the sample cell measured in an equilibrium period were always kept within (10-3 to 10-4) Kmin-1 during the acquisition of all heat-capacity data. The data of heat capacities and corresponding equilibrium temperature have been corrected for heat exchange of the sample cell with its surroundings.6 The sample mass used for calorimetric measurements was 3.3156 g, which was equivalent to 0.01537 mol in terms of its molar mass, M = 215.72 g mol-1. 2. 4. Differential Scanning Calorimetry (DSC) DSC analysis was carried out in a Perkin-Elmer diamond DSC. Sample with the mass of 4.67 mg was weighed in a closed pan, placed in the DSC cell, and heated at the rate of 5 K min-1 under the high-purity nitrogen with a flow rate of 30 mL min-1. 3. Results and Discussion 3. 1. Structural Description The molecular structure of N, N-dimethylnorephed-rine hydrochloride (C11H18NOCl) is plotted in Figure 1. The dimensions of the crystal used for X-ray diffraction data collection are given in Table 1. It is found out from Table 1 that the crystal system of the compound is orthor- Figure 1. Structure of N, N-dimethylnorephedrine hydrochloride (C11H18NOa) (s) hombic, the space group is P212121, unit cell parameters are a = 7.2486(19) À, b = 9.6741(^) À, c = 16.952(5) À; a = 90°, ß = 90°, Y = 90°, and Z = 4. Table 2 give non-hydrogen atomic coordinates (x104) and equivalent isotropic displacement parameters (À2 x 103). U (eq) is defined as one third of the trace of the orthogonalized U^tensor, which is equal to thermal parameters relative to the struc- Table 1. Crystallographic data and structure refinement for the title compound Crystallographic data structure refinement Empirical formula Formula weight Temperature Wavelength Crystal system space group Unit cell dimensions Volume Z Calculated density Absorption coefficient F(000) Crystal size 6 range for data collection Limiting indices Reflections collected / unique Completeness to theta = 25.00 Refinement method Data / restraints / parameters Goodness-of-fit on F2 Final R indices [I > 2 sigma (I)] R indices (all data) Absolute structure parameter Largest diff. peak and hole C11H18NOa 215.7^ 298(2)K 0.71073 À Orthorhombic P212121 a = 7.2486(19) À, b = 9.674(3) À, c = 16.952(5) À; a= 90°, ß= 90°, Y= 90° 1188.7(5) À3 4 1.205 mg/m3 0.292 mm-1 464 0.32 x 0.27 x 0.25 mm 2.40 to 25.00° -8 < h < 7, -11 < k < 11, -15 < l < 20 4940/2080 [R (int.) = 0.0220] 99.9 % Full-matrix least-squares on F2 2080/0/131 0.996 ^1=0.0318, wR2 = 0.0797 R1= 0.0389, w/R2 = 0.0848 -0.03(7) 0.115 and -0.196 e À-3 Table 2. Non-hydrogen atomic coordinates (x104) and equivalent isotropic displacement parameters (À2 x 103) Atoms U (eq) Cl(1) N(1) O(1) C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) C(10) C(11) -159(1) 3744(2) 2934(2) 6010(3) 4098(3) 2523(3) 2333(3) 1425(3) 1378(3) 2223(3) 3079(3) 3134(3) 3657(3) 5044(4) 3409(1) 6792(2) 5119(1) 6651(2) 7091(2) 6519(2) 7416(2) 8679(2) 9568(2) 9201(2) 7946(2) 7050(2) 5299(2) 7555(2) 1205(1) 3558(1) 2005(1) 2427(1) 2692(1) 2177(1) 1445(1) 1501(1) 854(1) 159(1) 95(1) 734(1) 3776(1) 4085(1) 51(1) 37(1) 49(1) 45(1) 35(1) 37(1) 35(1) 40(1) 47(1) 52(1) 55(1) 45(1) 51(1) 51(1) ture of the compound. Selected bond lengths and angles are listed in Table 3. The geometries of the hydrogen bonding are listed in Table 4. As shown in Figure 2, the symmetric unit consists of four N, N-dimethylnorephedrine chlorides. Two different kinds of hydrogen bonds N1-H1...a1 and O1-H1A...a1 exist in the packing structure of N, N-dimethylnorephed-rine hydrochloride form a network structure. The bond distances of N1-C2(1.518 À), N1-C10(1.492 À), N1-C11 (1.494 À), O1-C3(1.417 À), N1-H1(0.910 À), and O1-H1 A(0.820 À) are shorter than the normal mean bond distances of N-C(1.52 À), O-C(1.43 À), N-H(1.04 À) and O-H(0.96 À), respectively. This can be ascribed to the formation of the intermolecular hydrogen bonds, which makes these chemical bonds involved in the formation of the hydrogen bonds slightly move towards the centralization of electron clouds, shortening of bond lengths and strengthening of bond energies. Bond angle of O1-C3-C2 is 107.72° and deviates from regular tetrahedron angle 109.28°, which may also result from the forming of intermolecular hydrogen bonds. In addition, the bond length of C-C in the benzene ring of N, N-dimethylnorephedrine hydrochloride is slightly lower than that of normal value 1.396 À in the regular benzene ring , the difference may be assigned to the benzene ring in the title compound placing in a distinctly different surroundings from a regular benzene ring and the influence of tertary ammonium ion, chloride ion and hydroxyl group with polarity on the whole molecule structure. These results reveal that interactions of hydrogen bonds between the molecules play a critical role in formation, stability and crystallization of the cluster. Figure 2. Packing of N, N-dimethylnorephedrine hydrochloride (C11H1„NOa) (s) in unit cell 3. 2. Heat Capacity All experimental results were listed in Table 5 and plotted in Figure 3. It can be seen from Figure 3 that the heat capacity curve was smooth and continuous in the temperature region from 80 to 390 K and no thermal anomaly appeared. Experimental molar heat capacities in the temperature region of 80-390 K were fitted by the least square method and a polynomial equation of heat ca- Table 3. Bond lengths [À] and angles [°] N(1)-C(10) 1.492(2) C(2)-H(2) 0.9800 C(8)-C(9) 1.388(3) N(1)-C(11) 1.494(3) C(3)-C(4) 1.519(3) C(8)-H(8) 0.9300 N(1)-C(2) 1.518(2) C(3)-H(3) 0.9800 C(9)-H(9) 0.9300 N(1)-H(1) 0.9100 C(4)-C(9) 1.385(3) C(10)-H(10A) 0.9600 O(1)-C(3) 1.417(2) C(4)-C(5) 1.390(3) C(10)-H(10B) 0.9600 O(1)-H(1A) 0.8200 C(5)-C(6) 1.395(3) C(10)-H(10C) 0.9600 C(1)-C(2) 1.518(3) C(5)-H(5) 0.9300 C(11)-H(11A) 0.9600 C(1)-H(1B) 0.9600 C(6)-C(7) 1.375(3) C(11)-H(11B) 0.9600 C(1)-H(1C) 0.9600 C(6)-H(6) 0.9300 C(11)-H(11C) 0.9600 C(1)-H(1D) 0.9600 C(7)-C(8) 1.368(3) C(2)-C(3) 1.540(3) C(7)-H(7) 0.9300 C(10)-N(1)-C(11) 110.87(16) C(3)-C(2)-H(2) 106.2 C(7)-C(8)-C(9) 120.3(2) C(10)-N(1)-C(2) 115.57(15) O(1)-C(3)-C(4) 113.41(16) C(7)-C(8)-H(8) 119.9 C(11)-N(1)-C(2) 112.20(15) O(1)-C(3)-C(2) 107.72(15) C(9)-C(8)-H(8) 119.9 C(10)-N(1)-H(1) 105.8 C(4)-C(3)-C(2) 108.93(15) C(4)-C(9)-C(8) 120.6(2) C(11)-N(1)-H(1) 105.8 O(1)-C(3)-H(3) 108.9 C(4)-C(9)-H(9) 119.7 C(2)-N(1)-H(1) 105.8 C(4)-C(3)-H(3) 108.9 C(8)-C(9)-H(9) 119.7 C(3)-O(1)-H(1A) 109.5 C(2)-C(3)-H(3) 108.9 N(1)-C(10)-H(10A) 109.5 C(2)-C(1)-H(1B) 109.5 C(9)-C(4)-C(5) 118.84(19) N(1)-C(10)-H(10B) 109.5 C(2)-C(1)-H(1C) 109.5 C(9)-C(4)-C(3) 121.78(18) H(10A)-C(10)-H(10B) 109.5 H(1B)-C(1)-H(1C) 109.5 C(5)-C(4)-C(3) 119.27(17) N(1)-C(10)-H(10C) 109.5 C(2)-C(1)-H(1D) 109.5 C(4)-C(5)-C(6) 119.99(19) H(10A)-C(10)-H(10C) 109.5 H(1B)-C(1)-H(1D) 109.5 C(4)-C(5)-H(5) 120.0 H(10B)-C(10)-H(10C) 109.5 H(1C)-C(1)-H(1D) 109.5 C(6)-C(5)-H(5) 120.0 N(1)-C(11)-H(11A) 109.5 C(1)-C(2)-N(1) 112.74(16) C(7)-C(6)-C(5) 120.2(2) N(1)-C(11)-H(11B) 109.5 C(1)-C(2)-C(3) 114.09(16) C(7)-C(6)-H(6) 119.9 H(11A)-C(11)-H(11B) 109.5 N(1)-C(2)-C(3) 110.75(16) C(5)-C(6)-H(6) 119.9 N(1)-C(11)-H(11C) 109.5 C(1)-C(2)-H(2) 106.2 C(8)-C(7)-C(6) 120.0(2) H(11A)-C(11)-H(11C) 109.5 N(1)-C(2)-H(2) 106.2 C(8)-C(7)-H(7) 120.0 H(11B)-C(11)-H(11C) 109.5 Table 4. Hydrogen bonding data [À.and deg.] D-H d(D-H)/A d(H •A)/A