DE19936731C1 - Spectrometric or electrochemical determination of isocyanates, e.g. in atmosphere of workplace or chemical store, uses 7-piperazine-2,1,3-benzooxadiazole compound with electronegative group in 4-position as reagent - Google Patents

Abstract

Determination of isocyanates comprises contacting a sample with a reagent and optionally a buffer and evaluating the reaction by an ultraviolet/visible, fluorescence or mass spectrometric or electrochemical method. The reagent is a 4-nitro-, 4-sulfamoyl, 4-(N,N-dimethylsulfamoyl) or 4-sulfo-7-piperazino-2,1,3-benzooxadiazole (I). Determination of isocyanates comprises contacting a sample with a reagent and optionally a buffer and evaluating the reaction by an ultraviolet/visible, fluorescence or mass spectrometric or electrochemical method. The reagent is a 4-nitro-, 4-sulfamoyl, 4-(N,N-dimethylsulfamoyl) or 4-sulfo-7-piperazino-2,1,3-benzooxadiazole of formula (I); R = nitro (-NO2), sulfamoyl (-SO2NH2), N,N-dimethylsulfamoyl (-SO2N(CH3)2) or sulfo (-SO3H).

Description

The invention relates to a method for determining Isocyanates.

Isocyanates are important raw materials in the chemical industry. Most of the isocyanate production is for subsequent Synthesis of polyurethanes used, as a rule Diisocyanates reacted with diols in an addition reaction become. Isocyanates are for a larger number of work-related Asthma cases responsible than any other group of Chemicals. Exposure of workers to the Isocyanate and polyurethane production, when heating polymers or when spraying coating base materials through the Inhalation of vapors or aerosols take place.

For these reasons the control of the isocyanate concentration is on industrial jobs of particular importance and require the use of powerful analytical methods. Also investigations are directly in the production processes and for product control rely on appropriate analytical data.

A large number of analytical approaches have therefore become available in recent decades Methods for the determination of isocyanates developed, the The focus is on the analysis of air samples and aerosols.

The analytical methods are characterized by two general strategies for the determination of isocyanates: On the one hand, the Addition reaction of the isocyanates to alcohols or amines under Formation of the corresponding urethanes or urea derivatives exploited, on the other hand, the isocyanates after acidic hydrolysis determined to amines with the known methods of amine analysis become.

The latter strategy is used particularly with the so-called Marcali Method (K. Marcali, Analytical Chemistry 29 552 (1957)) used,  where isocyanates in an acidic solution in a wash bottle be hydrolyzed. The subsequent detection is carried out by Diazotization and coupling with N-2-aminoethyl-1-naphthylamine an intensely colored azo dye that is UV / vis spectroscopic detection is accessible. The simple one Photometric detection are minor disadvantages Selectivity and the lack of differentiation between different isocyanates.

The strategy of an addition reaction with alcohols or amines leads to the formation of stable urethanes or urea derivatives. To liquid chromatographic separation is quasi simultaneous determination of several isocyanates possible. The However, detection limits are largely dependent on those used Depending on derivatization reagents. So the reaction of the Isocyanates with ethanol or dibutylamine ("DBA", for example in M. Spanne, H. Tinnerberg, M. Dalene, G. Skarping, Analyst 121 1095 (1996)) on products whose UV / vis-spectroscopic properties given the lack of chromophoric groups from those of the derivatized isocyanates are dependent. While the UV / vis Spectroscopic determination of aromatic isocyanates is promising, the detection limits are Derivatization of aliphatic isocyanates is not sufficient. For the Selectivity and the possibility of simultaneous determination of different isocyanates also ensures an upstream liquid chromatographic separation.

Most reagents known in the literature are based on the Reaction between secondary amines with chromophores or fluorophore functional groups and the isocyanates. As Chromogenic derivatization reagents are, for example, N- (4- Nitrobenzyl) -n-propylamine ("Nitro Reagent", K.L. Dunlap, R.L. Sandridge, J. Keller, Analytical Chemistry 48, 497 (1976)), 1- (2- Methoxyphenyl) piperazine ("MP", C.J. Warwick, D.A. Bagon, C.J. Purnell Analyst 106 676 (1981)) or 1- (2-pyridyl) piperazine ("PP", P.A. Goldberg, R.F. Walker, P.A. Ellwood, H.L. Hardy, Journal of  Chromatography 212 93 (1981)), while 9- (N- Methylaminomethyl) anthracene ("MAMA", C. Sangö, E. Zimerson, Journal of Liquid Chromatography 3 971 (1980)), tryptamine (P.M. Eller, M.E. Cassinelli (ed.), NIOSH Manual of Analytical Methods, Method No. 5522: Isocyanates, National Institute for Occupational Safety and Health, Cincinnati, OH, 4th edn. (1996)) or 9- (1- Methylanthracenyl) piperazine ("MAP", R.P. Streicher, J.E. Arnold, M.K. Ernst, C.V. Cooper, American Industrial Hygiene Association Journal 57 905 (1996)) and 9- (1-methylanthracenyl) -4,4'-bipiperidine (R. P. Streicher, United States Patent, Patent Number 5,354,689) as fluorogenic reagents are used.

Some of these reagents are also electrochemical Destination accessible, especially the MP. A Mass spectrometric determination is known from the literature for the DBA (D. Karlsson, M. Spanne, M. Dalene, G. Skarping, Analyst 123 117 (1998)).

Using bis-4- (dimethylamino) phenyl methyleneimine hydrochloride in combination with a non-volatile basic Nitrogen compound as a catalyst on a support material (Paper, plastic film, silica gel) can be applied Breathing air at workplaces through a color reaction on their Isocyanate content to be examined (B. Westrup, J. Marcoll, DE 34 07 687 C1). A distinction between different ones However, isocyanates are not possible with this process.

All of the methods described above are characterized by serious disadvantages, for example too small Stability of the derivatives, toxic reagents, an expensive Sample preparation or insufficient detection limits. Under Taking into account the fact that in high performance Liquid chromatography (HPLC) of the UV / vis detector with decency on is most widespread, the present invention Task based on a new method for determining To develop isocyanates that are characterized by a boring  UV / vis absorption and high extinction coefficients. Additional fluorescence properties or the possibility of Mass spectrometric detection of the derivatives would be desirable.

Benzooxadiazole ("Benzofurazane") with an electron-withdrawing Group in 4-position and a reactive group in 7-position in the past few years as fluorogenic and chromogenic Derivatization reagents for the determination of a large number of Analyte groups have been described (P. B. Ghosh, M. W. Whitehouse, Biochemistry Journal 108 155 (1968); K. Imai, Y. Watanabe, Analytica Chimica Acta 130 377 (1981)). Particularly widespread these reagents are now used for the determination of amines (H.-J. Klimisch, L. Stadler, Journal of Chromatography 90 141 (1974)) and Amino acids (L. Johnson, S. Lagerkvist, P. Lindroth, M. Almhoff, K. Martinsson, Analytical Chemistry 54 939 (1982)), but also from Carbonyl compounds (S. Uzu, S. Kanda, K. Imai, K. Nakashima, S. Akiyama, Analyst 115, 1477 (1990); G. Gübitz, R. Wintersteiger, R. W. Frei, Journal of Liquid Chromatography 7 839 (1984); A. Büldt, U. Karst, Analytical Chemistry 71 1893 (1999); A. Büldt, R. Lindahl, J.-O. Levin, U. Karst, Journal of Environmental Monitoring 1 39 (1999); A. Büldt, U. Karst, DE 198 00 537.7 (1998)). Imai and A few years ago, employees used 4-nitro-7-piperazino-2,1,3- benzooxadiazole ("NBD-PZ") and 4-dimethylaminosulfonyl-7-piperazino- 2,1,3-benzooxadiazole ("DBD-PZ") as fluorescent reagents for Determination of carboxylic acids described (T. Toyo'oka et al., Journal of Chromatography 588 61 (1991). A use of Benzooxadiazoles as derivatization reagents for the determination of However, isocyanates are not yet known from the literature.

Surprisingly, however, it was found that 4-nitro-7-piperazino-2,1,3-benzooxadiazole ("NBD-PZ"), 4-dimethylamino sulfonyl-7-piperazino-2,1,3-benzooxadiazole ("DBD-PZ "), 4-aminosulfonyl-7-piperazino-2,1,3-benzooxadiazole (" ABD-PZ ") and 7-piperazino-2,1,3-benzooxadiazole-4-sulfonate (" SBD-PZ ") with isocyanates react rapidly with the formation of the corresponding urea derivatives, which can be easily separated by liquid chromatography on reverse phases and can be detected by UV / vis spectroscopy, fluorescence spectroscopy and mass spectrometry. An electrochemical (amperometric) detection of the derivatives, preferably the NBD-PZ derivatives, is also possible. The structure of the reagents is as follows:

with R = -NO ₂ , -SO ₂ NH ₂ , SO ₂ N (CH ₃ ) ₂ or -SO ₃ H.

The method according to the invention is initially based on the implementation the derivatization reagent with the analytes. This implementation can take place in the presence of a buffer. The Derivatization reagent is used for the analysis of vapors or aerosols in the form of its solution in wash bottles or Impingern or in the form of solid phases coated with reagent. Both sampling tubes and Passive collection systems, filters or denuders can be used. Means In an air sampling pump, an air flow with the reagent in Brought in contact. After the reaction, the reaction solution from wash bottles or impingers directly or after previous Extraction can be injected into an HPLC system. The coated Solid phases are with a suitable solvent or Solvent mixture, preferably XXX eluted and then in the HPLC injected. Reverse phase HPLC using the Gradient elution is used to separate the derivatives from the reagent particularly well suited. The subsequent detection can both UV / vis spectroscopic, as well as fluorescence spectroscopic, electrochemical (amperometric) or mass spectrometric respectively. The use of chemical is in mass spectrometry  Ionization under atmospheric pressure (APCI) or the electrospray Ionization (ESI) is particularly advantageous. The calibration takes place using external or internal standards.

The method according to the invention is distinguished in comparison to all of them o. g. Process through excellent UV / vis spectroscopic Characteristics from that in the case of the particularly advantageous NBD-PZ by absorption maxima between 478 and 486 nm and Extinction coefficient of 27600 L / mol.cm for mono- and 41200 bis 54100 L / mol for diisocyanate derivatives.

The use of the method according to the invention is intended below are explained using examples:

1) Determination of the concentration of hexamethylene diisocyanate (HDI) in a production plant

The concentration of HDI in the breathing area of a worker in a polyurethane manufacturing company is to be checked. For the investigations, the reagent NBD-PZ is first synthesized as follows:

• - To prepare NBD-PZ 1.79 g (20.8 mmol) of piperazine in 80 mL methanol presented. The piperazine solution presented then 1.0 g of 4-chloro-7-nitro-2,1,3-benzooxadiazole (5 mmol), previously dissolved in 60 mL trichloromethane using a Dropped funnel. The one that fails in the reaction The crude product is filtered off, washed with water and methanol and then recrystallized from acetonitrile.

Elemental analysis:
calculated:
C 48.19%; H 4.45%; N 28.10%;
found:
C 47.80%; H 4.33%; N 28.15%.

EIMS (m / z (rel. Int.), 70 eV):
249 (100), 297 (76), 172 (41), 131 (27), 104 (5), 56 (17); 29 (7).

UV / vis: λ _max = 486 nm
ε (λ _max ) = 21400 L / mol.cm

¹ H NMR (DMSO-d ₆ , TMS): 8.45 (d, 1H, H ₅ ); 6.64 (d, 1H, H _6); 4.08 (m, 4H, H _{2 '} , H _6' ); 2.92 (m, 4H, H _{3 '} , H _5' )

Melting point: 231 ° C.

Air sampling is done using reagent coated sampling tubes. These are made as follows:

• - To prepare coated sampling tubes, 0.138 g NBD-PZ is dissolved in 100 mL acetonitrile. A 5.6.10 ^-3 mol / L solution of the reagent is obtained. An octadecyl-modified silica gel is used to coat the reagent. Each sample tube is first conditioned with 1 mL acetonitrile and then coated with 5 mL of the reagent solution. After the solution has passed the tubes, they are dried in a stream of nitrogen for 30 minutes.

In a production hall of a chemical company that Manufactures polyurethanes at chest height of over 120 workers Minutes of air sampling at a sampling rate of one liter per minute using an air sampling pump sucked over the sampling tube. To break through the Detecting analytes through the sampling tube becomes a second identical sample tube connected in series.

After sampling, each tube is eluted with 10 mL acetonitrile / DMSO (70:30, v: v). An aliquot of 20 µL is injected into the HPLC system. The HPLC separation takes place under the following conditions:

• - A SUPELCO-DISCOVERY-RP-18 with a Particle size of 5 microns and a pore size of 200 Å used. The column dimensions are 150 mm × 4.6 mm. The dimensions of the  Guard column are 20 mm × 4 mm. To record the chromatogram a binary gradient of acetonitrile and water is used. The injection volume is 20 µL. The column is at 40 ° C tempered.

The detection of the reaction products is carried out by UV / vis spectroscopy at a wavelength of 480 nm. The chromatograms obtained are evaluated via the peak areas. The bis (urea derivative) of the HDI is used as the calibration standard, which is synthesized as follows:

• - 0.250 g of NBD-PZ (1 mmol) are placed in a flask and placed in 60 mL dichloromethane dissolved. Then dissolve 41 µL HDI (0.25 mmol) in 3 mL dichloromethane and give this solution for presentation. The The reaction product is obtained by adding 40 mL n-hexane in portions failed. The crude product is suctioned off, with water and methanol washed and recrystallized from acetonitrile.

Using the external calibration, a content of 30 µg / m ³ HDI in the air sample is determined. A breakthrough in the control tube cannot be detected.

2. Screening chemical warehouse with LC / MS and LC / UV

In a chemical warehouse, possible isocyanates in the Indoor air can be identified and quantified.

First, a solution of NBD-PZ (preparation see Example 1) with a concentration of 2.7. 10 ^-3 mol / L in acetonitrile. A sampling and a control wash bottle are transferred to 30 mL each. With an air sampling pump, an air flow from the chemical store of 800 mL / min is conveyed through the wash bottles connected in series. After a sampling time of 60 minutes, an aliquot of 20 μL is injected into the HPLC system and separated under the conditions given in Example 1. The detection is done mass spectrometrically using an APCI interface in positive mode. The selected ion monitoring (SIM) traces of the urea derivatives of the following isocyanates are selected to identify the corresponding substances: phenyl isocyanate (PI), 2,4-tolylene diisocyanate (2,4-TDI), 2,6-tolylene diisocyanate, hexamethylene diisocyanate ( HDI), methylene bis (phenyl isocyanate) (MDI) and isophorone diisocyanate (IPDI). The corresponding urea derivatives of the NBD-PZ were produced for the target analytes in order to ensure unambiguous identification via peak position, mass and UV / vis properties (a UV / vis detector is connected in series in front of the mass spectrometer).

On the basis of the measurement data, PI, 2,4-TDI and 2,6-TDI were clearly in the air sample can be identified. The others above Isocyanates could not be detected in the air sample. The The isocyanates were quantified in parallel by means of external ones Calibration for both types of detectors and additionally by internal Calibration with the MDI derivative after MDI is not in the sample could be demonstrated.

The concentrations of the three derivatives were determined by mass spectrometry to be 40 µg / m ³ for PI, 55 µg / m ³ for 2,4-TDI and 60 µg / m ³ for 2,6-TDI.

Claims (4)

1. A method for determining isocyanates, characterized in that a sample with a reagent of the formula with R = -NO ₂ , -SO ₂ NH ₂ , SO ₂ N (CH ₃ ) ₂ or -SO ₃ H
and optionally contacting a buffer and evaluating the reaction UV / vis-spectroscopic, fluorescence-spectroscopic, electrochemical or mass spectrometric. 2. A method for determining isocyanates according to claim 1, characterized in that after the reaction a chromatographic or electrophoretic separation takes place. 3. A method for determining isocyanates according to claim 1, characterized in that the reagent in the form of a solution in an organic or aqueous / organic solvent or in Form of a solid phase coated with reagent. 4. Method for determining isocyanates according to at least one of claims 1 and 3, characterized in that an air or Aerosol sampling for isocyanates using reagent filled wash bottles or impinger, or using with Reagent for coated sampling tubes, passive collectors or Denuder is carried out.