Synthesis of 3-Alkyl Oxazolidines, Derived from 2-Hydroxymethyl Piperidine, as Analytical Standards for the Analysis of Volatile Aldehydes in the Workplace.

Hexahydro-3-alkyl-3H-oxazolo[3,4-a]pyridines 4-15 for the quantitative analysis of various aldehydes were obtained in good yield via the condensation reaction of 2-hydroxymethylpiperidine (2-HMP) with aldehydes under mild conditions. When acrolein was used, the bicyclic 17 was obtained. This novel compound has suitable physical characteristics for an analytical standard. The hexahydro-3-vinyl-3H-oxazolo[3,4-a]pyridine 16 can be obtained at higher temperatures using an excess of acrolein (3 equiv). Following the same procedure as for 16, but with an excess of 2-HMP (2 equiv), a diastereomeric mixture of 18/19, which are both bisadducts of 2-HMP with acrolein, was obtained. The latter mixture can be easily converted into pure 18. Mechanistically, a thorough 1H-NMR study did not show any evidence that the condensation reaction proceeded via an enamine. The reaction probably proceeded through an elusive hemiaminal and fleeting iminium ion, which underwent subsequent cyclization to give hexahydro-3-alkyl-3H-oxazolo[3,4-a]pyridines 4-16. The reaction pathways for the preparation of 4-18 are described.

Comprehensive methylene diphenyl diisocyanate (MDI) evaluation method comparison using a laboratory generation system.

Isocyanates are reactive semivolatile contaminants that must be assessed in occupational environments, and specific evaluation methods are required to address the challenges related to isocyanate emission characteristics. Several standard methods exist, but significant differences remain regarding the diversity of industrial isocyanate emissions. This study presents a method to establish a baseline comparison of three sampling principles. A fine aerosol (mass median aerodynamic diameter of 250 nm) of pure methylene diphenyl diisocyanate (MDI) was produced (5-60 µg m-3) using a laboratory generation system (n = 31 generation experiments). Airborne MDI was measured with the following four methods, with an emphasis on the spatial distribution of the collected MDI within the sampler: (1) Swinnex cassette 13 mm, glass fibre filter (GFF), 9-(N-methylaminomethyl) anthracene (MAMA-Swin); (2) closed-face cassette (CFC) 37 mm, GFF (end filter and inner walls), MAMA-37; (3) impinger and backup GGF, 1,2-methoxyphenylpiperazine (MP) (ISO 16702/MDHS 25); and (4) denuder and GFF (Asset EZ4-NCO), dibutylamine (DBA) (ISO 17334-1). Bland and Altman analyses determined that there were no significant bias between the methods although Asset was not in agreement with MAMA-Swin (95% confidence interval above the ±20% criteria). Significant correlations (P < 0.05) were observed between airborne MDI concentration levels and their distribution within the Asset (denuder vs. end filter) and impinger (collecting solution vs. backup filter) subsections. The presence of impregnated inner walls in the CFC did not increase collection efficiency for the generated MDI aerosol. Non-uniform MAMA impregnation on GFF was demonstrated, whereas the collected MDI was evenly distributed in the air samples. These results provided the basis of comparison for other studies involving more complex isocyanate emissions.

Development of a new SPE UPLC-MS/MS method for extraction and quantitation of toluene diamine on gloves following toluene diisocyanate exposure.

RATIONALE: Toluene diisocyanate (TDI) is a highly reactive isocyanate commonly used as a mixture of 2,4- and 2,6- isomers in the production of flexible foams. Exposure to TDI occurs primarily through vapour inhalation in workplaces where TDI is produced or used, but dermal exposure is also possible during some tasks. To ensure workplace safety, accurate monitoring of TDI and toluene diamine (TDA) levels is required. Methods of quantifying field effectiveness of gloves in preventing dermal exposure have not been established. Therefore, there is a need to develop a new practical method for assessing glove effectiveness for TDI/TDA. METHOD: A new offline SPE UPLC-MS/MS method for the quantitation of TDA isomers from TDI-exposed gloves was developed. Gloves were dipped in a solution of 1% acetic acid leading to a full conversion to TDA. TDA-free amine compounds were derivatized with acetic anhydride to increase chromatographic retention and signal intensity. RESULTS: 2,4-Diaminotoluene-α, α, α-d3 (2,4-d3 -TDA) was selected as a surrogate standard to minimise the variability in sample preparation and instrumental sensitivity. The choice of UPLC-MS/MS operated in multiple reaction monitoring (MRM) mode allowed to reach much lower limits of detection (LOD). The LOD of the method was 6.86 and 2.83 ng/mL (0.03 and 0.01 µg) for 2,6-TDA and 2,4-TDA, respectively. The limit of quantitation (LOQ) was 22.85 and 9.42 ng/mL (0.11 and 0.05 µg) for 2,6-TDA and 2,4-TDA, respectively. CONCLUSION: A new UPLC-MS/MS analytical method has been developed to determine field effectiveness of gloves for preventing dermal exposure to TDI/TDA. The new technique overcomes some limitations for measuring putative dermal exposure to isocyanates and may be useful in exposure monitoring and future research on isocyanate health risks.

Development and characterization of an adaptable aerosolized methylene diphenyl diisocyanate generation system.

Reactive semivolatile contaminants, such as isocyanates, can be particularly difficult to assess in occupational environments. While standard methods exist for isocyanates, there are still significant differences between the results they provide for various occupational environments or processes. This study presents the validation of a laboratory system for the generation of controlled atmospheres of isocyanates. A system consisting of different modules generated airborne methylene diphenyl diisocyanate (MDI) by nebulizing a solution into mixing and exposure chambers with control of flow rate, temperature, and relative humidity. Sampling was performed through an eight-port flow splitter that allowed only very slight within-test variability. MDI was measured using the Asset EZ4-NCO® and a modified version of the Iso-Chek® sampling system. MDI specific particle-size distribution was measured by a Marple Sierra cascade. Aerosol real-time monitoring was performed using a condensation particle counter, an electrical low-pressure impactor (ELPI+), and an aerosol optical spectrometer, providing additional information on system stability and particle-size distribution of the generated aerosol. The system was able to generate MDI concentration levels ranging from 4 to 233 µg m-3, with a steady-state level reached within 5 minutes, and with well-documented intra-test and inter-test variability (RSD of 4% and 15%, respectively). Accuracy and representativeness of MDI data were confirmed by the agreement between MAMA and Asset EZ4-NCO (used as reference), with a mean bias of 3%. Using the Asset EZ4-NCO capability, the vapor-particle partitioning of MDI was evaluated to be 8% and 92%, respectively, at a concentration ranging from 20 to 25 µg m-3. The system may therefore be used for exhaustive method intercomparison studies and could also be adapted to generate other emission types of semivolatile compounds.

On-site comparison of the OSHA 47, Asset EZ4-NCO, Iso-Chek, DAN, and CIP10 methods for measuring methylene diphenyl diisocyanate (MDI) at an oriented-strand board (OSB) factory.

Diisocyanates are occupational contaminants and known sensitizers causing irritation (skin and respiratory tract) as well as occupational asthma. Because of their physicochemical properties (semi-volatile and high reactivity) and low occupational limits, diisocyanate exposure evaluation is still a challenge nowadays for industrial hygienists and laboratories. The objective of this study was to compare the methylene diphenyl diisocyanate (MDI) concentrations measured by five methods using different collection or derivatization approaches in an oriented-strand board (OSB) factory. The methods used were: OSHA 47 (filter, 1-(2-pyridyl)piperazine) (OSHA), Asset EZ4-NCO (denuder and filter, dibutylamine) (Asset), Iso-Chek (double-filter, 9-(N-methylaminomethyl) anthracene and 1,2-methoxyphenylpiperazine), DAN (filter, 1,8-diaminonaphthalene), and CIP10 (centrifugation, 1,2-methoxyphenylpiperazine). Real-time monitoring of particle concentration and size distribution was performed to explain the potential bias between methods. The comparison study was performed over 3 consecutive days, generating at least 18 replicates for each of the 5 methods. The results of each methods were compared using linear mixed effect modeling. Compared to Asset, which yielded the highest concentrations overall, the OSHA method provided the smallest bias with -18% (95% CI [-61;24]) (not significant) for MDI monomer and the DAN method provided the smallest bias with -30 (95% CI [-70;9]) (not significant) for Total Reactive Isocyanate Group (TRIG). The CIP10 and Iso-Chek methods provided the largest biases for MDI monomer (-83% (95% CI [-115;-51]) and -78% (95% CI [-110;-46]), respectively) as well as for TRIG (-87% (95% CI [-120;-55]) and -75% (95% CI [-107;-44]), respectively). The underestimations of the CIP10 and Iso-Chek were explained by its inefficient sampling principle for fines particles and the use of a non-impregnated filter to collect aerosol MDI, respectively. This study confirms that impregnated filter, including denuding device such as the Asset EZ4-NCO sampler, collects the MDI-coated wood particles and MDI vapor with similar efficiency. It also demonstrates for the first time in this type of MDI emission a significant agreement for TRIG concentration between the DAN method in the impregnated filter configuration and an international standard one such as Asset.

On site comparison of the OSHA 42, Asset EZ4-NCO, Iso-Chek, DAN and CIP10 methods for measuring toluene diisocyanate (TDI) at a polyurethane foam factory.

Because of the semi-volatile nature of diisocyanates (being airborne in both physical vapor and particulate phases), their high reactivity and low occupational exposure limits, diisocyanate exposure evaluation has been challenging for industrial hygienists and laboratories. The objective of this study was to compare the toluene diisocyanate (2,4 and 2,6 isomers, TDI) concentration measured by five methods in a flexible polyurethane foam factory using different collection or derivatization approaches. The methods used were: OSHA 42 modified (filter, 1-(2-pyridyl)piperazine) (OSHA), Asset EZ4-NCO (denuder and filter, dibutylamine) (Asset), Iso-Chek (double-filter, 9-(N-methylaminomethyl) anthracene and 1,2-methoxyphenylpiperazine), DAN (filter, 1,8-diaminonaphthalene), and CIP10 (centrifugation, 1,2-methoxyphenylpiperazine). Particle real-time monitoring for concentration and size distribution was performed in parallel to improve the understanding of the potential bias between methods. The comparison study was performed over 3 days, providing 18 replicates for each of the 5 methods. Isocyanate concentrations collected for each sampling method were compared using linear mixed effect modeling. Compared to OSHA, which yielded the highest concentrations overall, the Asset and DAN methods provided the smallest biases (-29% (95% CI [-52;-6]) and -45% (95% CI [-67;-23]), respectively), while the CIP10 and Iso-Chek methods provided the largest biases (-82% (95% CI [-105;-66]) and -96% (95% CI [-118;-75]), respectively). The substantial bias of Iso-Chek and CIP10 seemed to be explained by the predominance of TDI in the form of sub-micron particles that were inadequately captured by these two methods due to their sampling principle, which are particle filtration without derivatizing agent and centrifugation respectively. Asset and DAN performance seemed to decrease as the sampling time increased. While DAN's bias could be related to a reagent deficiency on the filter, the disparities between OSHA and Asset, both considered as reference methods, highlight the fact that the mechanisms of collection, derivation and extraction do not seem to be completely controlled. Finally, an upward trend has been observed between concentrations of particles below 300 nm in size and concentration levels of TDI. It has also been observed that TDI levels increased with the TDI foam index produced at the facility.

Development of a method for quantification of toluene diisocyanate and methylenediphenyl diisocyanate migration from polyurethane foam sample surface to artificial sweat by HPLC-UV-MS.

The US Environmental protection agency (EPA) has published guidance that includes test procedures for evaluating indoor exposure to chemicals from products. One of the test procedures represents the migration test for evaluating potential dermal exposure from home furniture. Such an evaluation involves the chemical measurement of the sweat which is currently unavailable in the literature. The objective of this project was to develop and validate an analytical method for quantification of migration of 4,4'-methylenediphenyl diisocyanate (MDI), 2,6-toluene diisocyanate (2,6-TDI) and 2,4-toluene diisocyanate (2,4-TDI) from a polyurethane (PU) flexible foam to artificial sweat that meets the recommendations of the EPA test protocol. Following the EPA protocol, six synthetic sweat solutions were prepared and used in evaluation of isocyanate recovery performance. The migration tests were conducted using five foam types that were chosen and supplied by PU foam manufacturers to represent the types most commonly found in commercial products, and with formulations anticipated to have the highest potential residual TDI or MDI. Migration tests were conducted using glass fiber filters (GFF) coated with 1-(2-methoxyphenyl)piperazine (1,2-MP) and analyzed using HPLC equipped with a UV detector for quantification and a MS detector to qualify peaks. The detection limits of the method were 0.002 µg/mL for 2,6-TDI, 0.011 µg/mL for 2,4-TDI, and 0.003 µg/mL for MDI. Quantification limits were 0.006 µg/mL, 0.037 µg/mL, and 0.010 µg/mL, respectively. The recovery tests on a Teflon surface for 5 of the 6 EPA-recommended synthetic sweat solutions indicate the recovery percentage was approximately 80% for diisocyanates. Recovery for the sixth sweat solution was low, approximately 30%. TDI and MDI migration was not observed when testing was conducted on foam samples.

An organic redox electrolyte to rival triiodide/iodide in dye-sensitized solar cells.

Dye-sensitized solar cells (DSCs) have achieved impressive conversion efficiencies for solar energy of over 11% with an electrolyte that contains triiodide/iodide as a redox couple. Although triiodide/iodide redox couples work efficiently in DSCs, they suffer from two major disadvantages: electrolytes that contain triiodide/iodide corrode electrical contacts made of silver (which reduces the options for the scale up of DSCs to module size) and triiodide partially absorbs visible light. Here, we present a new disulfide/thiolate redox couple that has negligible absorption in the visible spectral range, a very attractive feature for flexible DSCs that use transparent conductors as current collectors. Using this novel, iodide-free redox electrolyte in conjunction with a sensitized heterojunction, we achieved an unprecedented efficiency of 6.4% under standard illumination test conditions. This novel redox couple offers a viable pathway to develop efficient DSCs with attractive properties for scale up and practical applications.

Synthesis of 17 alpha-substituted ethynylestradiols: potential ligands for drug vectors.

17alpha-substituted ethynylestradiols, derived from estrone, were converted to their corresponding 17 alpha-(bromo- or iodo-propargyl)estrone intermediates. Nucleophilic substitution onto these moieties with malonate diester followed by hydrolysis and complexation with cis-Pt(Me(2)en)I(2) (Me(2)en=N,N-dimethylethylenediamine) gave cis-Pt(Me(2)en)(2-(3-(17beta-estradiol-17 alpha-yl)-prop-2-ynyl)malonato) 7, thus demonstrating that these estrogen-derived compounds can be used to synthesize stable Pt(II) complexes. The 3-(17beta-estradiol-17 alpha-yl)-prop-2-ynyl-1-sulfanylethylthiol 23 was also prepared.

Characterization of an abeo-taxane: brevifoliol and derivatives.

Brevifoliol is a natural diterpene isolated from Taxus baccata Nutt. A series of brevifoliol 1 derivatives, 2-8 and 10, were prepared for characterization and semisynthesis purposes and included the introduction of acetyl, Troc, and TES groups at C-5 and C-13. Derivatives 16-20 of 5-acetylbrevifoliol 2 were obtained via esterification with cinnamic acid, with both 2S-(-)- and 2R-(+)-3-phenyllactic acid, and with N-benzoyl-(2'R,3'S)-3'-phenylisoserine at C-13. Brevifoliol compounds 12, 13, and 15 with either 2S-(-)-phenyllactate moieties at C-5 and C-13 or an N-benzoyl-(2'R,3'S)-3'-phenylisoserinyl at C-13 were also prepared. An abeo-taxane structure for 1 was clearly defined from the (13)C NMR analysis of the 5-acetyl-13-oxo derivative 8 and from the conversion of 1 into 10, a conformationally restrained compound having a C-13, C-15 oxygen bridge. The biological activity of each of these derivatives is being studied.