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Synthesis of new microsensor coatings and their response to test vapors 2,4,6-trisubstituted-1,3,5-triazine derivatives
Talanta, Vol. 38, No. 5, pp. 535-540, 1991 F’rintcdin Great Britain. All rights reserved
0039.9140/91 $3.00 + 0.00
Copyright 0 1991Perganton Press plc
SYNTHESIS OF NEW MICROSENSOR COATINGS AND THEIR RESPONSE TO TEST VAPORS 2,4,6-TRISUBSTITUTED-1,3,5-TRIAZINE
DERIVATIVES
ALAN R. KATRITZKY,* JAMSHED N. LAMand HASSAN M. FAID-ALLAH Department of Chemistry, University of Plorida, Gainesville, FL 32611-2046, U.S.A. (Received
6 June 1990. Revised 30 October
1990. Accepted
3 November
1990)
Summary-Novel 1,3,5-triaxine derivatives were spray-coated onto surface acoustic wave (SAW) devices and exposed to vapors of dimethyl methylphosphonate (DMMP), chloroethyl ethyl sulfide (CEES) and ‘-water. Changes in chemiresistor and SAW responses were monitored and recorded by computer-controlled data-acquisition techniques. All the derivatives tested showed little or no chemiresistor or SAW responses to water vapor. The largest reversible chemiresistor response to DMMP vapor was observed with the dicarboxylic acid derivative. The largest SAW response to DMMP was with the dithione, and the dichloro-octylthio derivative showed the largest response. to CEES.
preliminary screening of heterocyclic derivatives and the behavior of various classes of compounds in an attempt to utilize these microsensors to their full potential. Heterocyclic systems tested so far include benzimidazole,” pyridine and pyrylium,” thiadiazole,13 nicotinamide,14 acridinium betaine,” and phosphor& derivatives. It is hoped that acquisition of such data will provide valuable insight into the vapor/coating interactions and afford a better understanding of the effects of various functional groups on the device responses. In this paper, we report the responses of a variety of trisubstituted-1,3,5triazines to DMMP (a nerve-agent simulant), CEES (a sulfur mustardgas simulant) and water (an interferent).
The need to design instruments to detect airborne contaminants has increased rapidly in recent years. The need to detect contaminants in parts per million (ppm) concentrations for gas leaks, chemical warfare (CW) agents and illicit drug manufacture makes the use of CC/MS (which has been used for the detection of atmospheric pollutants) and other large monitoring devices impractical. Microelectronics and computer design have been used in the fabrication of selective and sensitive vapor detectors which are small in size and are applicable to military, industrial and environmental use. These devices include chemiresistor,‘** surface acoustic wave (SAW)‘5 and bulk-wave piezoelectric quartz crystal sensors.6 The chemiresistor and SAW devices are both manufactured from piezoelectric quartz with an interdigitated electrode array (usually gold) lithographically deposited on the surface of the quartz crystal.’ It is this similarity between the two devices that allows resistance (chemiresistor) and frequency (SAW) measurements to be made simultaneously.’ The principles of operation of SAW devices3**as well as those of chemiresistors’ have already been described in detail. Details of the system used in our laboratory and its modes of operation have been published in two reviews by our group9*i0 and will not be discussed here. The work described in this report is part of a project involving rapid
EXPERIMENTAL
Simultaneous chemiresistor and SAW measurements were performed while exposing the device to water, CEES and DMMP vapors in turn. The results were usually reproducible to within 5%. The dual 52-MHz surface acoustic wave apparatus used (Microsensor Systems, Inc.), has been described in detail previously.9,“.‘5 The resonant frequency was monitored with a digital frequency counter, Phillips Model PM 6674 universal frequency counter (550 MHz). The conductivity measurements were made by the application of a I-V bias to either of the two remaining electrodes, and measurement of the current with a precision current-to-voltage
*Author for correspondence. 535
536
ALAN R. KATRITZKY et al.
converter consisting of an operational amplifier and a switch-selectable feedback resistor. SAW and chemiresistor data-acquisition was controlled by an Apple II computer with an IEEE-488 interface, connected to the frequency counter and an electrometer (Keithley 617 Programmable Electrometer). The coatings were dissolved in a volatile organic solvent, typically spectroscopic grade chloroform, and the device was spray-coated with an air brush, with dry nitrogen as the propellent. The coating thickness was monitored with the frequency counter until a frequency shift of cu. 50 kHz was obtained. The frequency shifts caused by the coating were recorded as an indication of coating thickness. Test vapors were generated by passing a regulated flow of nitrogen through the neat liquid at O”, in a vapor bubbler equipped with a gas dispersion tube. The flow-rate over the device was controlled with a flowmeter and was found to be 7.5 ml/min by use of a bubble meter. The absolute concentrations of the test vapors were calculated by methods described previously.‘5 Thus at O”, the vapor pressures of DMMP, CEES and water afforded concentrations of 5.2, 30.7 and 4.8 g/m3 respectively. Initially the system was purged with nitrogen for 5 min to establish a baseline curve. The device was then exposed to the vapor for 40 min, followed by a nitrogen purge for 50-60 min. If a response was irreversible, the SAW device was cleaned and recoated before exposure to the next test vapor. The SAW devices used were rinsed with acetone between runs, followed by ultrasonic cleaning for 15 min in spectroscopic grade 2-propanol. Melting points were determined on a Thomas-Hoover capillary melting point apparatus, and were uncorrected. ‘H NMR spectra were recorded on a Varian Model EM 360L spectrometer with tetramethylsilane (TMS) as the internal standard. 13C NMR spectra were recorded at 25 MHz on a JEOL Model JNMFX 100, with solvent peaks (CDCl,, 677.0 or (CD&SO 6 39.5) as internal references. Synthesis of coating materials
2,4-Dichloro-6-octylthio- 1,3,5-triazine (5), b.p. 140-145”/5 mmHg, literature value” 146-148”/0.4 mmHg, and 2,4-dichloro-6-dodecylthio-1,3,5-triazine (8), literature value” m.p. 23-26” (see Tables 1 and 2) were prepared by known literature procedures.
Preparation of 2,4-dioctylamino-boctylthio1,3,5triazine (2). A solution of 2,4-dichloro-6-
octylthio-1,3,5-triazine (15.0 g, 50 mmole) in acetone (50 ml) and water (20 ml) was cooled to O-5”. Octylamine (13.1 g, 110 mmole) was added dropwise while the temperature was maintained at O-5”. Cooling was continued as aqueous sodium hydroxide solution (2M, 50 ml) was slowly added. The mixture was then stirred for 24 hr at ambient temperature and the precipitate was filtered off, washed with water and dried. Crystallization from dilute methanol resulted in colorless plates (22.5 g, 93%), m.p. 56” (see Tables 1 and 2). Preparation of 4(3H),6(5H)-dithione
2-octylthio-1,3,5triazine(3). A solution of 2,4-
dichloro-6-octylthio-1,3,5-triazine (8.0 g, 27 mmole) and thiourea (4.0 g, 54 mmole) in acetone (100 ml) was heated under reflux for 1 hr. The reaction mixture was then cooled to 0” and aqueous sodium carbonate solution (0.5M, 200 ml) was added slowly, with the temperature kept below 5”. The mixture was then stirred at room temperature overnight, the precipitate filtered off and the filtrate neutralized with 5% v/v hydrochloric acid. The product was filtered off, washed with water and dried (see Tables 1 and 2). Preparation of 2,4-di(carboxymethylthio)-6octylthio- (6) and 2,4-di(carboxymethylthio)-6 dodecylthio- (9) 2,3,5triazines. A solution of (5)
or (8) (50 mmole) in acetone (100 ml) was cooled to O-5”. Mercaptoacetic acid (9.3 g, 100 mmole) and then collidine (13.5 g, 110 mmole) were added dropwise while the temperature was maintained at O-5”. The mixture was stirred for 24 hr at ambient temperature, poured into water (100 ml) and extracted with diethyl ether (3 x 75 ml). The ethereal solution was dried over anhydrous sodium sulfate and evaporated under reduced pressure to yield the products, as white solids (see Tables 1 and 2). General procedure for the synthesis of tris(dialkylaminoethylthioethoxy)- 1,3,5triazines (7a-c)
The appropriate dialkylaminoethanethiol hydrochloride (140 mmole) was added to a solution of cyanuric chloride (4) (8.7 g, 47 mmole) in acetone (100 ml). The mixture was cooled to O-5” and aqueous sodium hydroxide solution (2M, 140 ml) was added slowly so that the temperature remained at O-5”. After the addition was complete, the reaction mixture was stirred for 24 hr at ambient temperature, poured into water (75 ml), and extracted with diethyl
53-l
Synthesis of new microsensor coatings
ether (3 x 50 ml). The combined ether extracts were washed with water (25 ml) and dried over anhydrous sodium sulfate. Removal of the ether under reduced pressure gave the triazine derivatives (7a-c) as sticky oils which were then converted into the picrates and characterized. Each picrate was then dissolved in dichloromethane and washed with aqueous sodium hydroxide solution to afford the pure product (see Tables 1 and 2).
RESULTS AND DISCUSSION
Derivatives of the 1,3,5triazines, such as cyanuric acid (l), were discovered as early as 1776,18 although the parent compound 1,3,5-triazine was identified only much more recently by Grundmann and Kreutzberger.19 The most important precursor for the synthesis of 1,3,5-triazine derivatives is cyanuric chloride (4) the substituents in which can be displaced readily by nucleophiles to afford trisubstituted- 1,3,5_triazines. Thus symmetrical tri(alkylthio)- and tri(arylthio)-triazines have
0
been prepared by the reaction of sodium mercaptides with (4).20 We have now found that treatment of (4) with various dialkylaminoethanthiols at 0” in the presence of sodium hydroxide gives the trithioethers (7) in yields of 83-90%. The compounds were characterized by elemental analysis and their characteristic NMR spectra. In all three cases, the single aromatic carbon signal appeared between 178.7 and 179.4ppm. The aliphatic N-C, carbon atom in NCH&H$ showed an upfield shift of about 6.7 ppm as the dialkylamino substituent was changed from methyl to ethyl to isopropyl. The N-C, carbon atom of the isopropyl substituent (7~) gave a shift 3 ppm downfield from the signal for the dimethyl (7a) and diethyl (7b) derivatives. Previous workers found that the use of a weaker base such as collidine” or pyridine2’ and equimolar amounts of cyanuric chloride and a thiol or an alcohol, led to the displacement of a single chlorine atom to give monosubstituted adducts, which with other nucleophiles, formed unsymmetrical trisubstituted triazines.
N’+%-b7
A Ii 1,,HN’N’SC.,,, H
2
1
3
I Cl
Cl
SCH$OOH A c
Cl
SW-47
H00C(CH2)SA:j\SC8H17
6
SWzMJR2
A
R
2N(CH2)2S’:j\S,,H2,2NR2
7
’ C,”
Cl
SCH2COOH
A N
A SC12H25
8
a) R=Me b) Fi= Et c) R = i-Pr seheme 1
HOOC;CH2)S’ikC,2Hz
9
ALANR.
538
KATRITZKY
et al.
Table 1. Preparation of 2,4,6-trisubstituted-1,3,5-triazines Found (Theory), % Compound No.
Yield, %
M.P., “C
Crystal form
Recryst. solvent
Molecular formula
2
93
56
Plates
dil. MeOH
3
63
155
Microcrystals
Hz0
5 6
93 89
Oil 163
Needles
dil. MeOH
7a
83
Oil*
-
-
7b
87
Oilt
-
-
C,,H,N,S,
Pit
7c
90
Oils
-
-
C,,H,N&
. Pit
8 9
92 79
Oil 152-153
Needles
C,H, /MeOH
C
H
N
65.5 (65.21) 45.7 (45.67)
11.0 (10.80)
14.1 (14.11) 14.5 (14.53) -
42; (42.55) 38.0 (38.20) (Z3) 49.0 (49.19)
(64& (Zl) (44;:) (El) $0)
(El) 19.6 (19.80) 17.8 (17.47) 15.9 (15.70)
49.2 (49.43)
*M.P. of picrate 205”. tM.P. of picrate 76”. 3M.P. of picrate 162”.
As expected, reaction of cyanuric chloride with equimolar amounts of octanethiol or dodecylthiol in the presence of collidine afforded the monosubstituted thioethers (5) and (8) respectively. The remaining two chlorine atoms in (5) were readily displaced by octylamine in the presence of sodium hydroxide to give 4,6-di(octylamino)-2-octylthiotriazine (2). Reaction of (5) and (8) with mercaptoacetic acid, with collidine as the base, formed (6) and (9) in yields of 89 and 79% respectively. With two equivalents of thiourea, (5) gave the dithione derivative (3). Compounds 2,3 and 5-9 were then tested as microsensor coatings by exposure to DMMP, CEES and water vapors (Table 3). The frequency shifts were calculated by subtracting the lowest frequency recorded during vapor exposure from the initial (baseline) frequency. Resistance changes were the ratios of the initial
resistance to the lowest resistance recorded over the same period (thus, a value close to unity denotes no change). The low signal to noise ratio in the SAW device enables small frequency changes to be detected quite readily. Typically, for an SAW delay line operating in the frequency range of 30-300 MHz, mass changes of the order of 10m9g can be detected. However, for chemiresistor devices, a lOO-fold change is required for a compound to be considered a good coating. A large reversible resistance change (351fold) on exposure to DMMP was observed with 2,4-dicarboxymethylthio-6-octylthio-1,3,5-triazine (6) as the coating. The dodecylthio analog (9) showed a comparable change (283-fold). This large resistance change is not surprising since the presence of two carboxylic acid groups would be expected to result in some interaction with an ester group. What is surprising though
Table 2. ‘H and “C NMR data for 2,4,6-trisubstituted-s-triazines Compound No. 2 3 5 6 7a 7b
7c 8 9
‘H 5.26(2H, bs), 3.3(68, m), 1.33(36H, bs), 0.9(9H, t, J = 7Hz) 9.50(28, bs), 3.25(28, t, J = 7Hz), l.l5(12H, m), 0.75(38, t, J = 7Hz) 3.20(2H, t, J=lHz), 1.3(12H, bs), 0.90(3H, t, J = 7Hz) 6.7(2H, bs), 3.90(48, s), 3.15(2H, t, J = 7Hz), 1.30(12H, bs), 0.92(38, t, J = Hz) 3.29(6H, t, J = 7Hz), 2.60(68, t, J = 7Hz), 2.30(188, s) 3.3-2.3(248, m), l.O5(18H, t, J = 7Hz) 2.95(188, m), l.O5(36H, t, J = 7Hz) 3.2(2H, m), 1.75(28, m), 1.25(188, bs), 0.85(3H, t, J = 7Hz) 8.3(28. bsj. 3.95(48. s). 3.15(2H. t. J = Hz). 1.2{20fi, kj, 0.8$3ti, ;; J = ?Hzj ”
‘3C 164.5, 164.1, 41.2, 40.6, 31.8, 30.5, 29.7, 29.2, 26.9, 22.6 and 14.0. 177.3, 164.6, 31.3, 30.0, 28.5, 28.3, 28.0, 27.1 and 14.0. 186.3, 169.7, 31.5, 30.9, 28.8, 28.7, 28.4, 28.2, 22.4 and 13.8. 179.0, 178.6, 169.8, 33.5, 31.2, 29.6, 28.6, 28.0, 22.1 and 13.9 179.2, 58.0, 45.1 and 27.9. 178.8, 51.2, 46.4, 27.5 and 11.5. 179.4, 48.6, 44.5, 31.3 and 20.7. 186.5, 169.9, 31.8, 31.1, 29.5, 29.3, 29.0, 28.9, 28.7, 28.6, 28.3, 22.6 and 14.0. 179.2. 178.4, 169.4. 33.1. 31.3, 29.7 29.1,28.9, i8.6, 2s.1, 2i.l and 13.8
539
Synthesis of new microsensor coatings Table 3. Response of 2.4,~trisubstituted-1,3,5-triazines to test vapors Compound No.
Coating mass,*
Frequency shift, kHz
Resistance change factor
kHz
DMMP
CEES
H,O
DMMP
CEES
H,O
: 5
56 55 52
126.9 1.0 31.0
3.9 1.0 34.0
1.1 :.:
52.6 2.5 2;::
:.: 18:l
;: 0:3
6 7a
4-I 48
1.0 351.0
11.9 z
8:5 k!l
2.6
9.6 2.1
::;
7h 7c 8 9
53 54 50 55
20.8 15.0 5.2 283.0
22:3 37.4 2.4
1:s 1.0 8.0
z 4:1 17.4
1:: 4:9 1.3
z 0:3 0.7
*Frequency change equivalent to the mass.
is the fact that both these coatings showed a comparatively low response to water vapor (Fig. 1). Furthermore, both displayed good frequency responses to DMMP (27.2 and 17.4 kHz, respectively) indicating that there was a mass loading (absorption) effect. A large resistance change with a low frequency change would have implied a surface effect. The largest resistance change (37.4-fold) for CEES vapor was observed with 2,4-dichloro6-dodecylthio-1,3,5-triazine (8). The octylthio compound (5) also gave a high response (34.0-fold) to CEES and a similar response (37-fold) to DMMP vapor. Compound 8, however, did not show a comparable response to the DMMP vapor. The highest responses to water vapor were from the dicarboxylic acids (6) and (9), but these were still low, so these derivatives would make good chemiresistor coatings for the detection of DMMP vapors. The greatest SAW frequency response was with the dithione (3), which displayed a frequency shift of 52.6 kHz for DMMP and
_-
r
40-
fSOe - 20.E I: c 'Oif
O-
CEES
-104 . . . , . 0
20
40
60
80
100
Time (mid
Fig. 1. Chemiresistor response of: a, compound 6 and; b, compound 9 us. time, for exposure to DMMP and water vapor.
60
SO
I
100
Time (mid
had good discrimination, shown by its small response to CEES and water vapors (Fig. 2). Furthermore, it was 90% reversible. Consequently, this makes it a very good coating for an SAW device in the detection of DMMP in the presence of CEES and water vapors. A sharp change in frequency when the vapor is turned on and off is shown in Fig. 3. After purging of the
. . 0
0
40
Fig. 2. Frequency response of 2-octylthio-1,3,5-triaxine4(3H),6(5H)-dithione (3) us. time, for exposure to vapor.
-5 102
. , . . . , . . . , . . . ,
20
.
. . 20
.
. . 40
.
. .
. 60
. .
.
. . 80
.
..I 100
Time (mid
Fig. 3. Frequency response of 2-octylthio-1,3,5-triazine.4(3H),6(5H)dithione (3) OS. time for periodic vapor exposure to DMMP (on/off time interval 5/2 min until t = 48 min, then IO/4 mitt until I = 90 mitt).
540
ALAN
R.
KMRITZKY
system with nitrogen for 5 min the vapor was repeatedly turned on for 5 min and then off for 2 min over a period of 40 min. The on/off times were then changed to 10 and 4 min respectively for a further 60 min. Analysis of the results shows that for both absorption and desorption the change in frequency is a quadratic function of time (with correlation factors of 0.992 and 0.997 respectively). The dicarboxylic acids (6) and (9) also showed good selectivity, displaying a large response only to DMMP vapor. For CEES vapor, the largest response was with the dichloro-octylthio compound (5) with low responses towards DMMP and water, thus displaying potential as a coating for the detection of CEES vapors. However, the dodecyl derivative (8) showed poor responses to all three vapors. Previous work in our group13 has shown that within series of dimethyl-, diethyl- and di-isopropyl-amino derivatives, the frequency response to CEES decreases, indicating that steric hindrance around the amino group is an important factor for interaction with CEES vapor. Interestingly, in the present case, the tris(N,N-di-isopropylamino) analog (7~) showed the greatest response of the three. This further highlights the fact that there is still a lack of understanding of the precise interactions between coatings and vapors. In all cases when a high response to DMMP or CEES vapor occurred, there was a low response to water vapor, indicating a low interference by humidity. The moderate to good solubility of these triazine derivatives in chloroform caused no difficulties in the spraying of these coatings. The relatively low volatility (as indicated by a baseline drift of ca. 1 kHz/hr, which is normal in a laboratory environment without temperature control), indicated a negligible tendency of the coating to vaporize when exposed to air, and hence the possibility of a reasonable lifetime, since the responses were reversible. The coating thicknesses were much the same for all the triazines tested. Although a thicker coating would display a larger response, owing to the greater number of sorption sites, there are other factors such as shear modulus and film mass-density that come into play. The
et a/.
vapor diffusion rate and device response times are closely related,’ and very close packing (high mass-density) of the coating would hinder easy diffusion of the analyte and the corresponding response time would be greater. It is for this reason that we have chosen not to study the relation between coating thickness and response times. Acknowledgement-We thank G. Paul Savage for his help ful advice in this work and his suggestions in the preparation of this manuscript. REFERENCES
1. H. Wohltjen, W. R. Barger, A. W. Snow and N. L. Jarvis, IEEE Tranx Electron Devices, 1985, ED-320, 1170. T. E. Edmonds and T. S. West, Anal. Chim. Acta, 1980, 117, 147. H. Wohltjen, Sens. Actuators, 1984, 5, 307. C. T. Chuang, R. M. White and J. J. Bernstein, IEEE Electron Device L&t., 1982, EDL-3(6), 145. A. Venema, E. Nieuwkoop, M. J. Vellekoop, M. S. Nieuwenhuizen and A. W. Barendsz, Seas. Actuators, 1986, 10, 47. 6. W. H. King, Jr., Anal. Chem., 1964, 36, 1735. I. A. W. Snow, W. R. Barger, M. Klusty, H. Wohltjen and N. L. Jarvis, Langmuir, 1986, 2, 513. 8. M. S. Nieuwenhuizen and A. W. Barendsz, Sens. Actuators, 1987, 11, 45. 9. A. R. Katritzky and R. J. Offerman, Crit. Rev. Anal. Chem., 1989, 2, 83. 10. A. R. Katritzky and G. P. Savage, Rev. Heteroatom Chem., 1990, 3, 160. 11. A. R. Katritzky, G. P. Savage, J. N. Lam and M. Pilarska, Chem. Ser., 1989, 29, 197. 12. A. R. Katritzky, G. P. Savage, M. Pilarska and 2. Dega-Szafran, ibid., 1989, 29, 235. 13. A. R. Katritzky, G. P. Savage and M. Pilarska, ibid., 1989, 29, 317. 14. A. R. Katritzky, G. P. Savage, M. Pilarska, N. S. Bodor and M. E. Brewster, ibid., 1989, 29, 319. 15. A. R. Katritzky, R. J. Offerman, J. M. Aurrecoechea and G. P. Savage, Talanta, 1990, 37, 911. 16. A. R. Katritzky, G. P. Savage, R. J. Offerman and B. Pilarski, ibid., 1990, 37, 921. 17. H. Koopman, J. H. Uhlenbroek, H. H. Haeck, J. Daams and M. J. Koopmans, Rec. Trav. Chim. Pays-Bas, 1959, 78, 967. 18. E. M. Smolin and L. Rapoport, in s-Triazines and Derivatives, A. Weissberger (ed.), Interscience, New York, 1959. 19. C. Grundmann and A. Kreutzberger, J. Am. Chem. Sot., 1954, 76, 632. 20. P. Klason, J. Prakt. Chem., 1886, 33, I 16. 21. J. R. Geigy A.-G., Brit. Patent, 977, 589, Dec. 9, 1964, U.S. Appl. April 12, Aug. 3, 1960, and Feb. 21, 1961; Chem. Abstr., 1965, 62, 11834d.
0039.9140/91 $3.00 + 0.00
Copyright 0 1991Perganton Press plc
SYNTHESIS OF NEW MICROSENSOR COATINGS AND THEIR RESPONSE TO TEST VAPORS 2,4,6-TRISUBSTITUTED-1,3,5-TRIAZINE
DERIVATIVES
ALAN R. KATRITZKY,* JAMSHED N. LAMand HASSAN M. FAID-ALLAH Department of Chemistry, University of Plorida, Gainesville, FL 32611-2046, U.S.A. (Received
6 June 1990. Revised 30 October
1990. Accepted
3 November
1990)
Summary-Novel 1,3,5-triaxine derivatives were spray-coated onto surface acoustic wave (SAW) devices and exposed to vapors of dimethyl methylphosphonate (DMMP), chloroethyl ethyl sulfide (CEES) and ‘-water. Changes in chemiresistor and SAW responses were monitored and recorded by computer-controlled data-acquisition techniques. All the derivatives tested showed little or no chemiresistor or SAW responses to water vapor. The largest reversible chemiresistor response to DMMP vapor was observed with the dicarboxylic acid derivative. The largest SAW response to DMMP was with the dithione, and the dichloro-octylthio derivative showed the largest response. to CEES.
preliminary screening of heterocyclic derivatives and the behavior of various classes of compounds in an attempt to utilize these microsensors to their full potential. Heterocyclic systems tested so far include benzimidazole,” pyridine and pyrylium,” thiadiazole,13 nicotinamide,14 acridinium betaine,” and phosphor& derivatives. It is hoped that acquisition of such data will provide valuable insight into the vapor/coating interactions and afford a better understanding of the effects of various functional groups on the device responses. In this paper, we report the responses of a variety of trisubstituted-1,3,5triazines to DMMP (a nerve-agent simulant), CEES (a sulfur mustardgas simulant) and water (an interferent).
The need to design instruments to detect airborne contaminants has increased rapidly in recent years. The need to detect contaminants in parts per million (ppm) concentrations for gas leaks, chemical warfare (CW) agents and illicit drug manufacture makes the use of CC/MS (which has been used for the detection of atmospheric pollutants) and other large monitoring devices impractical. Microelectronics and computer design have been used in the fabrication of selective and sensitive vapor detectors which are small in size and are applicable to military, industrial and environmental use. These devices include chemiresistor,‘** surface acoustic wave (SAW)‘5 and bulk-wave piezoelectric quartz crystal sensors.6 The chemiresistor and SAW devices are both manufactured from piezoelectric quartz with an interdigitated electrode array (usually gold) lithographically deposited on the surface of the quartz crystal.’ It is this similarity between the two devices that allows resistance (chemiresistor) and frequency (SAW) measurements to be made simultaneously.’ The principles of operation of SAW devices3**as well as those of chemiresistors’ have already been described in detail. Details of the system used in our laboratory and its modes of operation have been published in two reviews by our group9*i0 and will not be discussed here. The work described in this report is part of a project involving rapid
EXPERIMENTAL
Simultaneous chemiresistor and SAW measurements were performed while exposing the device to water, CEES and DMMP vapors in turn. The results were usually reproducible to within 5%. The dual 52-MHz surface acoustic wave apparatus used (Microsensor Systems, Inc.), has been described in detail previously.9,“.‘5 The resonant frequency was monitored with a digital frequency counter, Phillips Model PM 6674 universal frequency counter (550 MHz). The conductivity measurements were made by the application of a I-V bias to either of the two remaining electrodes, and measurement of the current with a precision current-to-voltage
*Author for correspondence. 535
536
ALAN R. KATRITZKY et al.
converter consisting of an operational amplifier and a switch-selectable feedback resistor. SAW and chemiresistor data-acquisition was controlled by an Apple II computer with an IEEE-488 interface, connected to the frequency counter and an electrometer (Keithley 617 Programmable Electrometer). The coatings were dissolved in a volatile organic solvent, typically spectroscopic grade chloroform, and the device was spray-coated with an air brush, with dry nitrogen as the propellent. The coating thickness was monitored with the frequency counter until a frequency shift of cu. 50 kHz was obtained. The frequency shifts caused by the coating were recorded as an indication of coating thickness. Test vapors were generated by passing a regulated flow of nitrogen through the neat liquid at O”, in a vapor bubbler equipped with a gas dispersion tube. The flow-rate over the device was controlled with a flowmeter and was found to be 7.5 ml/min by use of a bubble meter. The absolute concentrations of the test vapors were calculated by methods described previously.‘5 Thus at O”, the vapor pressures of DMMP, CEES and water afforded concentrations of 5.2, 30.7 and 4.8 g/m3 respectively. Initially the system was purged with nitrogen for 5 min to establish a baseline curve. The device was then exposed to the vapor for 40 min, followed by a nitrogen purge for 50-60 min. If a response was irreversible, the SAW device was cleaned and recoated before exposure to the next test vapor. The SAW devices used were rinsed with acetone between runs, followed by ultrasonic cleaning for 15 min in spectroscopic grade 2-propanol. Melting points were determined on a Thomas-Hoover capillary melting point apparatus, and were uncorrected. ‘H NMR spectra were recorded on a Varian Model EM 360L spectrometer with tetramethylsilane (TMS) as the internal standard. 13C NMR spectra were recorded at 25 MHz on a JEOL Model JNMFX 100, with solvent peaks (CDCl,, 677.0 or (CD&SO 6 39.5) as internal references. Synthesis of coating materials
2,4-Dichloro-6-octylthio- 1,3,5-triazine (5), b.p. 140-145”/5 mmHg, literature value” 146-148”/0.4 mmHg, and 2,4-dichloro-6-dodecylthio-1,3,5-triazine (8), literature value” m.p. 23-26” (see Tables 1 and 2) were prepared by known literature procedures.
Preparation of 2,4-dioctylamino-boctylthio1,3,5triazine (2). A solution of 2,4-dichloro-6-
octylthio-1,3,5-triazine (15.0 g, 50 mmole) in acetone (50 ml) and water (20 ml) was cooled to O-5”. Octylamine (13.1 g, 110 mmole) was added dropwise while the temperature was maintained at O-5”. Cooling was continued as aqueous sodium hydroxide solution (2M, 50 ml) was slowly added. The mixture was then stirred for 24 hr at ambient temperature and the precipitate was filtered off, washed with water and dried. Crystallization from dilute methanol resulted in colorless plates (22.5 g, 93%), m.p. 56” (see Tables 1 and 2). Preparation of 4(3H),6(5H)-dithione
2-octylthio-1,3,5triazine(3). A solution of 2,4-
dichloro-6-octylthio-1,3,5-triazine (8.0 g, 27 mmole) and thiourea (4.0 g, 54 mmole) in acetone (100 ml) was heated under reflux for 1 hr. The reaction mixture was then cooled to 0” and aqueous sodium carbonate solution (0.5M, 200 ml) was added slowly, with the temperature kept below 5”. The mixture was then stirred at room temperature overnight, the precipitate filtered off and the filtrate neutralized with 5% v/v hydrochloric acid. The product was filtered off, washed with water and dried (see Tables 1 and 2). Preparation of 2,4-di(carboxymethylthio)-6octylthio- (6) and 2,4-di(carboxymethylthio)-6 dodecylthio- (9) 2,3,5triazines. A solution of (5)
or (8) (50 mmole) in acetone (100 ml) was cooled to O-5”. Mercaptoacetic acid (9.3 g, 100 mmole) and then collidine (13.5 g, 110 mmole) were added dropwise while the temperature was maintained at O-5”. The mixture was stirred for 24 hr at ambient temperature, poured into water (100 ml) and extracted with diethyl ether (3 x 75 ml). The ethereal solution was dried over anhydrous sodium sulfate and evaporated under reduced pressure to yield the products, as white solids (see Tables 1 and 2). General procedure for the synthesis of tris(dialkylaminoethylthioethoxy)- 1,3,5triazines (7a-c)
The appropriate dialkylaminoethanethiol hydrochloride (140 mmole) was added to a solution of cyanuric chloride (4) (8.7 g, 47 mmole) in acetone (100 ml). The mixture was cooled to O-5” and aqueous sodium hydroxide solution (2M, 140 ml) was added slowly so that the temperature remained at O-5”. After the addition was complete, the reaction mixture was stirred for 24 hr at ambient temperature, poured into water (75 ml), and extracted with diethyl
53-l
Synthesis of new microsensor coatings
ether (3 x 50 ml). The combined ether extracts were washed with water (25 ml) and dried over anhydrous sodium sulfate. Removal of the ether under reduced pressure gave the triazine derivatives (7a-c) as sticky oils which were then converted into the picrates and characterized. Each picrate was then dissolved in dichloromethane and washed with aqueous sodium hydroxide solution to afford the pure product (see Tables 1 and 2).
RESULTS AND DISCUSSION
Derivatives of the 1,3,5triazines, such as cyanuric acid (l), were discovered as early as 1776,18 although the parent compound 1,3,5-triazine was identified only much more recently by Grundmann and Kreutzberger.19 The most important precursor for the synthesis of 1,3,5-triazine derivatives is cyanuric chloride (4) the substituents in which can be displaced readily by nucleophiles to afford trisubstituted- 1,3,5_triazines. Thus symmetrical tri(alkylthio)- and tri(arylthio)-triazines have
0
been prepared by the reaction of sodium mercaptides with (4).20 We have now found that treatment of (4) with various dialkylaminoethanthiols at 0” in the presence of sodium hydroxide gives the trithioethers (7) in yields of 83-90%. The compounds were characterized by elemental analysis and their characteristic NMR spectra. In all three cases, the single aromatic carbon signal appeared between 178.7 and 179.4ppm. The aliphatic N-C, carbon atom in NCH&H$ showed an upfield shift of about 6.7 ppm as the dialkylamino substituent was changed from methyl to ethyl to isopropyl. The N-C, carbon atom of the isopropyl substituent (7~) gave a shift 3 ppm downfield from the signal for the dimethyl (7a) and diethyl (7b) derivatives. Previous workers found that the use of a weaker base such as collidine” or pyridine2’ and equimolar amounts of cyanuric chloride and a thiol or an alcohol, led to the displacement of a single chlorine atom to give monosubstituted adducts, which with other nucleophiles, formed unsymmetrical trisubstituted triazines.
N’+%-b7
A Ii 1,,HN’N’SC.,,, H
2
1
3
I Cl
Cl
SCH$OOH A c
Cl
SW-47
H00C(CH2)SA:j\SC8H17
6
SWzMJR2
A
R
2N(CH2)2S’:j\S,,H2,2NR2
7
’ C,”
Cl
SCH2COOH
A N
A SC12H25
8
a) R=Me b) Fi= Et c) R = i-Pr seheme 1
HOOC;CH2)S’ikC,2Hz
9
ALANR.
538
KATRITZKY
et al.
Table 1. Preparation of 2,4,6-trisubstituted-1,3,5-triazines Found (Theory), % Compound No.
Yield, %
M.P., “C
Crystal form
Recryst. solvent
Molecular formula
2
93
56
Plates
dil. MeOH
3
63
155
Microcrystals
Hz0
5 6
93 89
Oil 163
Needles
dil. MeOH
7a
83
Oil*
-
-
7b
87
Oilt
-
-
C,,H,N,S,
Pit
7c
90
Oils
-
-
C,,H,N&
. Pit
8 9
92 79
Oil 152-153
Needles
C,H, /MeOH
C
H
N
65.5 (65.21) 45.7 (45.67)
11.0 (10.80)
14.1 (14.11) 14.5 (14.53) -
42; (42.55) 38.0 (38.20) (Z3) 49.0 (49.19)
(64& (Zl) (44;:) (El) $0)
(El) 19.6 (19.80) 17.8 (17.47) 15.9 (15.70)
49.2 (49.43)
*M.P. of picrate 205”. tM.P. of picrate 76”. 3M.P. of picrate 162”.
As expected, reaction of cyanuric chloride with equimolar amounts of octanethiol or dodecylthiol in the presence of collidine afforded the monosubstituted thioethers (5) and (8) respectively. The remaining two chlorine atoms in (5) were readily displaced by octylamine in the presence of sodium hydroxide to give 4,6-di(octylamino)-2-octylthiotriazine (2). Reaction of (5) and (8) with mercaptoacetic acid, with collidine as the base, formed (6) and (9) in yields of 89 and 79% respectively. With two equivalents of thiourea, (5) gave the dithione derivative (3). Compounds 2,3 and 5-9 were then tested as microsensor coatings by exposure to DMMP, CEES and water vapors (Table 3). The frequency shifts were calculated by subtracting the lowest frequency recorded during vapor exposure from the initial (baseline) frequency. Resistance changes were the ratios of the initial
resistance to the lowest resistance recorded over the same period (thus, a value close to unity denotes no change). The low signal to noise ratio in the SAW device enables small frequency changes to be detected quite readily. Typically, for an SAW delay line operating in the frequency range of 30-300 MHz, mass changes of the order of 10m9g can be detected. However, for chemiresistor devices, a lOO-fold change is required for a compound to be considered a good coating. A large reversible resistance change (351fold) on exposure to DMMP was observed with 2,4-dicarboxymethylthio-6-octylthio-1,3,5-triazine (6) as the coating. The dodecylthio analog (9) showed a comparable change (283-fold). This large resistance change is not surprising since the presence of two carboxylic acid groups would be expected to result in some interaction with an ester group. What is surprising though
Table 2. ‘H and “C NMR data for 2,4,6-trisubstituted-s-triazines Compound No. 2 3 5 6 7a 7b
7c 8 9
‘H 5.26(2H, bs), 3.3(68, m), 1.33(36H, bs), 0.9(9H, t, J = 7Hz) 9.50(28, bs), 3.25(28, t, J = 7Hz), l.l5(12H, m), 0.75(38, t, J = 7Hz) 3.20(2H, t, J=lHz), 1.3(12H, bs), 0.90(3H, t, J = 7Hz) 6.7(2H, bs), 3.90(48, s), 3.15(2H, t, J = 7Hz), 1.30(12H, bs), 0.92(38, t, J = Hz) 3.29(6H, t, J = 7Hz), 2.60(68, t, J = 7Hz), 2.30(188, s) 3.3-2.3(248, m), l.O5(18H, t, J = 7Hz) 2.95(188, m), l.O5(36H, t, J = 7Hz) 3.2(2H, m), 1.75(28, m), 1.25(188, bs), 0.85(3H, t, J = 7Hz) 8.3(28. bsj. 3.95(48. s). 3.15(2H. t. J = Hz). 1.2{20fi, kj, 0.8$3ti, ;; J = ?Hzj ”
‘3C 164.5, 164.1, 41.2, 40.6, 31.8, 30.5, 29.7, 29.2, 26.9, 22.6 and 14.0. 177.3, 164.6, 31.3, 30.0, 28.5, 28.3, 28.0, 27.1 and 14.0. 186.3, 169.7, 31.5, 30.9, 28.8, 28.7, 28.4, 28.2, 22.4 and 13.8. 179.0, 178.6, 169.8, 33.5, 31.2, 29.6, 28.6, 28.0, 22.1 and 13.9 179.2, 58.0, 45.1 and 27.9. 178.8, 51.2, 46.4, 27.5 and 11.5. 179.4, 48.6, 44.5, 31.3 and 20.7. 186.5, 169.9, 31.8, 31.1, 29.5, 29.3, 29.0, 28.9, 28.7, 28.6, 28.3, 22.6 and 14.0. 179.2. 178.4, 169.4. 33.1. 31.3, 29.7 29.1,28.9, i8.6, 2s.1, 2i.l and 13.8
539
Synthesis of new microsensor coatings Table 3. Response of 2.4,~trisubstituted-1,3,5-triazines to test vapors Compound No.
Coating mass,*
Frequency shift, kHz
Resistance change factor
kHz
DMMP
CEES
H,O
DMMP
CEES
H,O
: 5
56 55 52
126.9 1.0 31.0
3.9 1.0 34.0
1.1 :.:
52.6 2.5 2;::
:.: 18:l
;: 0:3
6 7a
4-I 48
1.0 351.0
11.9 z
8:5 k!l
2.6
9.6 2.1
::;
7h 7c 8 9
53 54 50 55
20.8 15.0 5.2 283.0
22:3 37.4 2.4
1:s 1.0 8.0
z 4:1 17.4
1:: 4:9 1.3
z 0:3 0.7
*Frequency change equivalent to the mass.
is the fact that both these coatings showed a comparatively low response to water vapor (Fig. 1). Furthermore, both displayed good frequency responses to DMMP (27.2 and 17.4 kHz, respectively) indicating that there was a mass loading (absorption) effect. A large resistance change with a low frequency change would have implied a surface effect. The largest resistance change (37.4-fold) for CEES vapor was observed with 2,4-dichloro6-dodecylthio-1,3,5-triazine (8). The octylthio compound (5) also gave a high response (34.0-fold) to CEES and a similar response (37-fold) to DMMP vapor. Compound 8, however, did not show a comparable response to the DMMP vapor. The highest responses to water vapor were from the dicarboxylic acids (6) and (9), but these were still low, so these derivatives would make good chemiresistor coatings for the detection of DMMP vapors. The greatest SAW frequency response was with the dithione (3), which displayed a frequency shift of 52.6 kHz for DMMP and
_-
r
40-
fSOe - 20.E I: c 'Oif
O-
CEES
-104 . . . , . 0
20
40
60
80
100
Time (mid
Fig. 1. Chemiresistor response of: a, compound 6 and; b, compound 9 us. time, for exposure to DMMP and water vapor.
60
SO
I
100
Time (mid
had good discrimination, shown by its small response to CEES and water vapors (Fig. 2). Furthermore, it was 90% reversible. Consequently, this makes it a very good coating for an SAW device in the detection of DMMP in the presence of CEES and water vapors. A sharp change in frequency when the vapor is turned on and off is shown in Fig. 3. After purging of the
. . 0
0
40
Fig. 2. Frequency response of 2-octylthio-1,3,5-triaxine4(3H),6(5H)-dithione (3) us. time, for exposure to vapor.
-5 102
. , . . . , . . . , . . . ,
20
.
. . 20
.
. . 40
.
. .
. 60
. .
.
. . 80
.
..I 100
Time (mid
Fig. 3. Frequency response of 2-octylthio-1,3,5-triazine.4(3H),6(5H)dithione (3) OS. time for periodic vapor exposure to DMMP (on/off time interval 5/2 min until t = 48 min, then IO/4 mitt until I = 90 mitt).
540
ALAN
R.
KMRITZKY
system with nitrogen for 5 min the vapor was repeatedly turned on for 5 min and then off for 2 min over a period of 40 min. The on/off times were then changed to 10 and 4 min respectively for a further 60 min. Analysis of the results shows that for both absorption and desorption the change in frequency is a quadratic function of time (with correlation factors of 0.992 and 0.997 respectively). The dicarboxylic acids (6) and (9) also showed good selectivity, displaying a large response only to DMMP vapor. For CEES vapor, the largest response was with the dichloro-octylthio compound (5) with low responses towards DMMP and water, thus displaying potential as a coating for the detection of CEES vapors. However, the dodecyl derivative (8) showed poor responses to all three vapors. Previous work in our group13 has shown that within series of dimethyl-, diethyl- and di-isopropyl-amino derivatives, the frequency response to CEES decreases, indicating that steric hindrance around the amino group is an important factor for interaction with CEES vapor. Interestingly, in the present case, the tris(N,N-di-isopropylamino) analog (7~) showed the greatest response of the three. This further highlights the fact that there is still a lack of understanding of the precise interactions between coatings and vapors. In all cases when a high response to DMMP or CEES vapor occurred, there was a low response to water vapor, indicating a low interference by humidity. The moderate to good solubility of these triazine derivatives in chloroform caused no difficulties in the spraying of these coatings. The relatively low volatility (as indicated by a baseline drift of ca. 1 kHz/hr, which is normal in a laboratory environment without temperature control), indicated a negligible tendency of the coating to vaporize when exposed to air, and hence the possibility of a reasonable lifetime, since the responses were reversible. The coating thicknesses were much the same for all the triazines tested. Although a thicker coating would display a larger response, owing to the greater number of sorption sites, there are other factors such as shear modulus and film mass-density that come into play. The
et a/.
vapor diffusion rate and device response times are closely related,’ and very close packing (high mass-density) of the coating would hinder easy diffusion of the analyte and the corresponding response time would be greater. It is for this reason that we have chosen not to study the relation between coating thickness and response times. Acknowledgement-We thank G. Paul Savage for his help ful advice in this work and his suggestions in the preparation of this manuscript. REFERENCES
1. H. Wohltjen, W. R. Barger, A. W. Snow and N. L. Jarvis, IEEE Tranx Electron Devices, 1985, ED-320, 1170. T. E. Edmonds and T. S. West, Anal. Chim. Acta, 1980, 117, 147. H. Wohltjen, Sens. Actuators, 1984, 5, 307. C. T. Chuang, R. M. White and J. J. Bernstein, IEEE Electron Device L&t., 1982, EDL-3(6), 145. A. Venema, E. Nieuwkoop, M. J. Vellekoop, M. S. Nieuwenhuizen and A. W. Barendsz, Seas. Actuators, 1986, 10, 47. 6. W. H. King, Jr., Anal. Chem., 1964, 36, 1735. I. A. W. Snow, W. R. Barger, M. Klusty, H. Wohltjen and N. L. Jarvis, Langmuir, 1986, 2, 513. 8. M. S. Nieuwenhuizen and A. W. Barendsz, Sens. Actuators, 1987, 11, 45. 9. A. R. Katritzky and R. J. Offerman, Crit. Rev. Anal. Chem., 1989, 2, 83. 10. A. R. Katritzky and G. P. Savage, Rev. Heteroatom Chem., 1990, 3, 160. 11. A. R. Katritzky, G. P. Savage, J. N. Lam and M. Pilarska, Chem. Ser., 1989, 29, 197. 12. A. R. Katritzky, G. P. Savage, M. Pilarska and 2. Dega-Szafran, ibid., 1989, 29, 235. 13. A. R. Katritzky, G. P. Savage and M. Pilarska, ibid., 1989, 29, 317. 14. A. R. Katritzky, G. P. Savage, M. Pilarska, N. S. Bodor and M. E. Brewster, ibid., 1989, 29, 319. 15. A. R. Katritzky, R. J. Offerman, J. M. Aurrecoechea and G. P. Savage, Talanta, 1990, 37, 911. 16. A. R. Katritzky, G. P. Savage, R. J. Offerman and B. Pilarski, ibid., 1990, 37, 921. 17. H. Koopman, J. H. Uhlenbroek, H. H. Haeck, J. Daams and M. J. Koopmans, Rec. Trav. Chim. Pays-Bas, 1959, 78, 967. 18. E. M. Smolin and L. Rapoport, in s-Triazines and Derivatives, A. Weissberger (ed.), Interscience, New York, 1959. 19. C. Grundmann and A. Kreutzberger, J. Am. Chem. Sot., 1954, 76, 632. 20. P. Klason, J. Prakt. Chem., 1886, 33, I 16. 21. J. R. Geigy A.-G., Brit. Patent, 977, 589, Dec. 9, 1964, U.S. Appl. April 12, Aug. 3, 1960, and Feb. 21, 1961; Chem. Abstr., 1965, 62, 11834d.