Solution and Solid State Thermal Stability of Morpholinedithiocarbamates

Estudos termogravimétricos e calorimétricos diferenciais de morfolinoditiocarbamatos de NH 4 +, Mn2+, Co2+, Ni2+ e Cu2+ foram realizados em atmosferas de ar e nitrogênio, para avaliar a influência da presença do oxigênio como heteroátomo no anel da amina na decomposição térmica. Produtos de decomposicão térmica foram caracterizados através de difratogramas de raios X, sendo predominantemente formados por sulfetos metálicos, sob atmosfera dinâmica de nitrogênio e óxidos metálicos, sob ar. Usando espectrofotometria, também foram determinados o pKa = 3,56 para o ácido morfolinoditiocarbâmico em força iônica 0,50 mol dm -3 (NaClO4) à 25,0 °C e parâmetros cinéticos de decomposição em diferentes valores de pH (k lim = 0,14 ± 0,04 s -1 e t1⁄2 lim = 5,3 ± 1,2 s).


Introduction
Recently, the interest in the stability of dithiocarbamates (DTC) has been renewed by the utilization of such compounds as coadjuvants in the treatment of AIDS 1,2 .They have also been suggested for tuberculosis 3 and cancer 4 treatment in the past.In these applications the compound must have enough chemical stability for an effective action in the biological medium.The DTC are obtained by the reaction between a primary or secondary amine with carbon dissulfide in a basic aqueous solution.The applications of this class of compounds in medicine, agriculture, industry, analytical and organic chemistry, as well as their physicochemical properties are summarized in several review articles [5][6][7][8][9][10][11][12][13][14] .From these works and references cited therein it is known that DTC derived from cyclic amines are more stable than the aliphatic derivatives.Additionally the thermal behavior is another important feature in industry and agriculture applications.
Since the decomposition of the DTC's is very fast in acidic media a spectrophotometric method based on diodearray measurements has recently been proposed 22 , for a more accurate determination of the pKa of dithiocabamic acids.A correlation between the infrared spectroscopy data of the coordination nature of cyclic DTC complexes and its effect in thermal decomposition of such compounds has also been presented 23,24 .
In this work, the pKa value of the morpholinedithiocarbamic acid (HMor) was determined (I = 0,50 mol dm -3 ), by absorption spectrophotometry in the ultra-violet region, and used to estimate the rate of decompostion of morpholinedithiocarbamate (Mor) in different pH values.The thermal behavior of solid state complexes of the type [MMor 2 ]•xH 2 O (M = Mn(II), Co(II), Ni(II) and Cu(II), x = 0 or 1.75) was studied in order to investigate the effect of the presence of an oxygen heteroatom in the amine ring and on *e-mail: cavalheiro@dq.ufscar.brparameters such as atomic radius of the metal center and character of coordination (mono or bidentate) on the thermal behavior.

DTC synthesis and characterization
The Mor ammonium salt was obtained by the reaction between the carbon disulfide and morpholine, in the presence of ammonium hydroxide 22,25 , in an ethanol/water 1:1 (v/v) reaction media.The white solid thus obtained was washed with cold ethanol and then crystallized by dissolving in water, followed by addition of ethanol.The solution was frozen and the white needle crystals formed were dried in a vacuum oven at 50°C for 8 h and characterized by vibrational spectroscopy and elemental analysis.

Buffer solutions
The McIlvaine buffer solutions with ionic strength adjusted to 0.50 mol dm -3 (NaClO 4 ) were prepared according to the procedure described by Elving et al 26 .

Equipment
Characterization of the complexes was performed by IR vibrational spectroscopy (KBr pellets) with a Bomem MB-102 spectrophotometer; flame atomic absorption spectroscopy was carried out in an Hitachi Z-8100 spectrophotometer and C,N,H contents were determined by elemental analysis using a Fisons EA 1108 CNHS-O instrument.
Thermogravimetric (TG) curves were recorded in a DuPont 9900 thermoanalyser coupled with a TGA 951 Thermogravimetric Module under a gas flow of 1.67 cm 3 s -1 (N 2 or air), in a platinum crucible, at 0.167 °C s -1 heating rate and using samples of about 7 mg of compound at atmospheric pressure.The differential scanning calorimetric (DSC) curves were recorded in a DuPont 9900 thermoanalyser coupled with a DSC 910 Calorimetric Module under a gas flow of 1.67 cm 3 s -1 (N 2 or air), in covered aluminum pans, at 0.167 °C s -1 heating rate and using samples of about 5 mg of compound at atmospheric pressure.The cell was previously calibrated for temperature and energy using indium metal (99.9+%) as standard.
Intermediates of thermal decomposition process were obtained in an oven at the same temperature and atmosphere that they appeared in the TG curves.After 15 min they were cooled down and kept in a dissecator under vacuum.The X-ray patterns of the crystalline residues were recorded in a VEB-Karl Zeiss Jena URD6 diffractometer.The results were compared with standard data from the International Centre for Diffraction Data, for characterization.
A diode-array Hewlett-Packard HP 8451A spectrophotometer and quartz cells, 1.00 cm path length, were used in the spectrophotometric measurements.The pH values were measured with a Corning IA 250 coupled to a Metrohm EA 121 combined glass electrode and X-ray diffraction patterns of intermediate and final products of thermal decomposition, with an HZG4-Karl Zeiss Jena diffractometer.

Procedure for pKa determination
The spectrophotometric method used for pKa determination was described earlier 22 .All the spectrophotometric measurements were carried at 25.0 ± 0.1 °C, using buffered solutions as blanks.Stock NH 4 Mor solutions (1.0x10 -2 mol dm -3 ) were used in the preparation of working solutions, with concentration ranging from 1.70 x 10 -5 to 8.40 x 10 -5 mol dm -3 at pH 2.66 and 5.22 NH 4 Mor solution 1.0 x 10 -4 mol dm -3 NH 4 Mor solution was used in the determination of the maximum absorption wavelength, of the acidic and basic forms, in pH ranging from 2.87 to 5.15.In order to minimize the decomposition of the compounds, the solutions were prepared directly in the cells.Thus an appropriate volume of the stock solution of NH 4 Mor was transferred with an automatic pipette and introduced in the buffer solution reaching a final volume of 3.00 cm 3 .

Results and Discussion
The prepared compounds are listed in Table 1 and the formulae given are in agreement with elemental analyses and thermogravimetric data.The ligand structure is presented in Figure 1 which also shows the structure of the 5 membered pyrrolidinedithiocarbamate (Pyr) and 6 membered piperidinedithiocarbamate (Pip) cyclic derivatives whose pKa and thermal decomposition data are compared to those of Mor.The unique hydrated complex was [CoMor 2 ]•1.75H 2 O.The presence of a nonstoichiometric amount of water weakly bonded to the complex is in agreement with previous observations for Co-DTC complexes 24 and is confirmed by a mass loss starting at the begning of the TG curves and by an endothermic process in DSC (Figures 2 and 3).
All the complexes showed a split IR absorption band around 1000 cm -1 , indicating that the ligand presents a monodentate behavior according to Sharma 6 and Nakamoto 28 .
The characteristic C-N stretching vibrational mode is observed at 1493-1415 cm -1 and is less intense than that Table 1.Percentages of carbon, hydrogen and nitrogen found and (calculated) and the main infrared bands (cm -1 ) for the morpholinedithio-carbamates studied in this work.observed for alkyl DTC derivatives due to the low double bond character caused by the rigid ring system 29 .The ν(C-O-C) vibration 30 in the ring appears around 1110 cm -1 .

pKa determination
The use of diode array data for pKa determination is convenient since the decomposition of DTC occurs very fast in acidic media [18][19][20][21] .The decomposition rate depends on the amine substituents.The procedure considers that the total absorbance at a given wavelength is due to the sum of the absorbances of the protonated (HMor) and free (Mor-) forms of the DTC: The maximum wavelength of the protonated HMor form was observed at 286 nm.The free form presented two maxima at 264 and 288 nm.For best resolution, 264 nm (basic, ε = 2.14 x 10 3 cm -1 mol dm -3 ) and 286 nm (acidic, ε = 2.06 x 10 3 cm -1 mol dm -3 ) were used in the pKa determination.The results are summarized in Table 2 and pKa = 3.56 ± 0.57 was obtained.
Values of pKa around 5.20 were previously reported, using polarographic 31 and spectrophotometric 32 methods, under different ionic strengths.An important point in favor of the present results are the changes in spectral shape when the pH is changed from 2.75 to 5.20 (Figure 4).According to Vandebeek et al 20 , the acidic form of a DTC presents only one peak in UV, while the basic form presents two peaks.Figure 4 shows that from pH 3.30 two peaks are clearly observed evidencing the presence of a significant amount of the basic form.If the pKa was 5.20, the ratio [Mor -]/[HMor] = 0.02 at pH 3.52 and only one peak should be observed at UV spectra at such conditions.

Decomposition kinetics
The decomposition of NH 4 Mor was followed by the absorbance decay of the peak at 286 nm at different pH values.The lnA/A 0 vs. time plots showed a linear dependence suggesting a pseudo-first order kinetics with slope equal to k ap .
The decomposition of dithiocarbamates was investigated by Chakrabarty and co-workers [18][19][20][21] .According to these authors the rate of decomposition in basic media is dependent of the pH ([H + ]<<Ka) but in sufficiently acidic solutions ([H + ]>>Ka) it becomes constant (k ap ≈ k lim ), according to: (4)   in which k ap is the apparent rate constant from ln A/A 0 vs. time plots, k lim is the limiting rate constant at low pH and Ka is the acidic dissociation constant.
The results obtained for Mor -, in Table 3, and show that the presence of the oxygen in the morpholine ring makes it less stable than the analogous piperidinedithiocarbamate (t ½lim = 10 s) and the 5 membered ring pyrrolidine derivative (t ½lim = 1620 s) 22 .

Thermal decomposition of solid state complexes
The thermal processes, residues formed, mass losses and temperature ranges observed in each step of the TG/ DTG and DSC curves are given in Table 4.When crystalline intermediates were obtained they have been characterized on the basis of their X-ray diffraction patterns, compared with literature data 33 (see Table 5).The TG/DTG and DSC curves are presented in Figure 2 under N 2 and in Figure 3 under air.600-700 20.9 b 20.5 _ a relative to mass loss; b relative to residue; c characterized by X-ray diffraction pattern -see Table 5; d CR = carbonaceous residue.decomposition are the corresponding sulfides and/or carbon.At higher temperatures the presence of carbon produced metallic Mn, Co and Ni and Cu 2 S for the respective DTC.The DSC peaks were in agreement with TG results.
Heating [MnMor 2 ] in a glycerin bath at 270°C in a 20 cm long glass tube led to the condensation of a white substance, whose IR spectrum suggested the presence of Mor -bands and whose decomposition is probably related with the loss of dithiocarbamate.
Although some DTG and DSC curves presented shoulders suggesting that the decomposition occurs in more than one step, stoichiometric calculations do not lead to the conclusion that decomposition proceeds via a thyocianate intermediate.This is in agreement with previous findings for piperidinedithiocarbamate 23,24 , also a 6-membered amine ring derivative.

b) Thermal decomposition under air
Under air [CoMor 2 ]•1.75H 2 O, [NiMor 2 ] and [CuMor 2 ] decomposed in a single step, according to the TG results presented in Figure 3. Depending on the metallic center in the complex, sulfides (Cu, Ni), oxides (Cu, Co) or sulfate (Mn) are the main products of thermal decomposition.These compounds are converted to the respective oxides at higher temperatures (see Table 4).
The manganese complexes showed a mass gain before decomposition.This is probably related to the addition of an oxygen atom to the complex, according to elemental analysis data, which may be related to the presence of sulfate as decomposition product in this case.
TG/DTG and DSC results confirmed the presence of water in [CoMor 2 ].The endothermic process at 310 °C in DSC of [CuMor 2 ] suggests an initial reduction of the metal at the beginning of the decomposition process.Other DSC peaks were in agreement with TG/DTG data.
In Table 6 starting decomposition temperatures are summarized for some [MMor] complexes (M = Co(II), Ni(II) and Cu(II)) in comparison with Pyr and Pip analogue complexes.These data suggest that the presence of the oxygen atom in the amine ring makes the Mor derivatives thermally more stable than Pip analogues.This should be related with the oxygen tendency to concentrate the electronic density thereby weakening the N-C bond in relation to Pip.The less tense 5-membered Pyr ring results in complexes more stable than the corresponding Mor and Pip complexes.

Conclusions
The presence of the oxygen as heteroatom in the amine ring makes HMor a stronger acid than the equivalent piperidinedithiocarbamic acid (HPip).The limiting half life (t 1/2 lim ) suggests that Mor -is slightly less stable than piperidinedithiocarbamate (Pip) and much less stable than pyrrolidinedithiocarbamate (Pyr) 23 .
In all complexes the ligand presented coordination in a monodentate way and [MnMor 2 ] was the only one that seemed to decompose via a thyocianate intermediate.The starting decomposition temperatures followed the order: Pyr>Mor>Pip for similar metallic complexes 24 under both atmospheres.
)where, A A and A B are the absorbances in the wavelengths A and B, respectively, ε A,HMor and ε A,Mor-are the molar absorptivities of the protonated and free forms in the wavelength A, and [HMor] and [Mor -] are the concentrations of the protonated and free forms, respectively.The absorptivity coefficients can be obtained from the slopes of A vs [Mor -] plots, at the maximum wavelengths in acidic and basic media.On solving equations (1) e (2), it is possible to determine the [Mor-]/[HMor] ratio.Then, measuring the absorbances at different pH values the pKa can be determined by the Henderson-Hasselbach equation:

Figure 3 .
Figure 3. TG (solid)/DTG(dashed) (a) and DSC (b) curves under air flow of 100 cm 3 min -1 , other conditions as in the text.
a) Thermal decomposition under nitrogen The ammonium salt showed complete volatilization between 105-205 °C, without residue on the crucible.IR spectra of the original and condensed salts confirmed the sublimation phenomena.Presence of hydration water in [CoMor 2 ] is confirmed in TG/DTG and DSC experiments.The TG curves of the metal complexes showed decomposition in a single step, except for [MnMor 2 ].The first products of thermal

Figure 4 .
Figure 4. Changes in the spectral shape of a 1.0 x 10 -4 mol dm -3 HMor solution, when the pH is changed from 2.75 to 5.20.
The metal complexes were obtained by direct reaction of the DTC ammonium salt and CuCl 2 .2H 2 O, NiCl 2 .6H 2 O, CoCl 2 .6H 2 O or MnCl 2 .2H 2 O.The resulting precipitates were filtered off, washed with water and then with ethanol.Finally they were dried and characterized as above.

Table 4 .
Thermal degradation data of the compounds in nitrogen and air atmospheres, in thermogravimetry, showing the thermal process, the interval of temperature (∆T), mass losses (∆m) obtained (obt) and calculated (clc), or residue (res) and by differential sacanning calorimetry, indicating the temperature of the peak (T), the nature of the endothermic (endo) or exothermic (exo) process.

Table 5 .
33ray data for the residues at different temperatures compared with literature standards33.

Table 6 .
Starting decomposition temperatures obtained form TG data for Mor complexes compared with Pyr and Pip analalogues.