Transformation of Acetaminophen by Chlorination Produces the Toxicants 1,4-Benzoquinone and N-Acetyl-p-benzoquinone Imine

Mary Bedner and William A. MacCrehan

Environ. Sci. Technol., 2006, 40 (2), pp 516–522
DOI: 10.1021/es0509073

Abstract

The reaction of the common pain reliever acetaminophen (paracetamol, 4-acetamidophenol) with hypochlorite was investigated over time under conditions that simulate wastewater disinfection. Initially, the reaction was studied in pure water at neutral pH (7.0), a range of reaction times (2?90 min), and a molar excess of hypochlorite (2?57 times) relative to the acetaminophen concentration. The reaction was monitored using reversed-phase liquid chromatography (LC) with ultraviolet absorbance, electrochemical, and mass spectrometric detection. At 1 ?mol/L (150 ppb) and 10 ?mol/L (1.5 ppm) levels, acetaminophen readily reacted to form at least 11 discernible products, all of which exhibited greater LC retention than the parent. Two of the products were unequivocally identified as the toxic compounds 1,4-benzoquinone and N-acetyl-p-benzoquinone imine (NAPQI), which is the toxicant associated with lethality in acetaminophen overdoses. With a hypochlorite dose of 57 ?mol/L (4 ppm as Cl2), 88% of the acetaminophen (10 ?mol/L initial) was transformed in 1 h. The two quinoidal oxidation products 1,4-benzoquinone and NAPQI accounted for 25% and 1.5% of the initial acetaminophen concentration, respectively, at a 1 h reaction time. Other products that were identified included two ring chlorination products, chloro-4-acetamidophenol and dichloro-4-acetamidophenol, which combined were approximately 7% of the initial acetaminophen concentration at 1 h. The reaction was also studied in wastewater, where similar reactivity was noted. These results demonstrate that acetaminophen is likely to be transformed significantly during wastewater chlorination. The reactivity of the chlorine-transformation products was also studied with sulfite to simulate dechlorination, and 1,4-benzoquinone and NAPQI were completely reduced.

A VERSATILE METHOD FOR THE CONVERSION OF OXIMES TO NITROALKANES

Synthetic communications
SUBHAS BOSE D. ; VANAJATHA G.
1998, vol. 28, no24, pp. 4531-4535

Abstract
A convenient oxidation of oximes to nitroalkanes has been developed using oxone® in acetonitrile

Synthesis of Aluminum Isopropoxide from Aluminum Dross

Korean Journal Chemical Engineering
Seung-Joon Yoo, Ho-Sung Yoon1,Hee Dong Jang, Jung-Woon Lee, Seung-Tae Hong, Min-Jae Lee, Se-Il Lee1 and Ki-Won Jun
Vol.23(4) 2006 pp.683-687
DOI: 10.1007/BF02706815

Abstract

Synthetic reaction of aluminum isopropoxide, which is used as a starting material for catalytic-grade alumina, has been studied in the presence of a small amount of HgI2, HgCl2, I2 or FeCl3 from aluminum dross. It was synthesized by solid-liquid reaction between the aluminum metal and isopropyl alcohol, using vacuum distillation process. The purity of the synthesized aluminum isopropoxide was obtained over 97.6% experimentally, which had been analyzed quantitatively by complexometric method. The initial amount of sodium, which directly affects the catalytic activation in the alumina catalyst, was in the range of 0.926 to 1.563 wt% in the aluminum dross. Finally, it was decreased to 0.007 wt% in the aluminum isopropoxide product. Yield was changed according to the amount of aluminium existing in the aluminum dross. Aluminum could mostly be recovered regardless of the amount of aluminium existing in the aluminum dross.

---

2BFRANK

Sorry for the misunderstanding.  I thought I was helping by not growing this thread out any further.

"Optimizing methylation conditions for gas liquid chromatography assay of lactic and succinic acid in biological samples"
K. S. Bricknell, I. Brook, and S. M. Finegold
Chromatographia
Volume 12, Number 1 / January, 1979
DOI: 10.1007/BF02271594

Thanks again to all of you for spending your valuable time chasing down papers for all of us.

Ok, it appears rules and designated format for making a request need to be reiterated...

Here goes - Java (and it is Java who does most of the work) needs people to ensure that they put their request in Blue, for those who don't know how to do that, it is simple - go to the drop down menu (above), the one that says 'Change Color', then choose blue. You will then see two pieces of code in square brackets, which say - excuse the lack of the square brackets, I'll use vertical straight lines instead (so where you see such a line, use a square bracket instead)

|color=blue|

|b||u|Title of the Article|/u||/b|

|i|Author(s)|/i|

Journal Name
Volume(edition) Year pp.220-330
DOI: xyfwihoqfehf987435

|u|Abstract|/u|

This is the way you WILL request journal articles, or they will not only be ignored, they will be deleted. If you want people to go to the time, effort and expense of accessing the article(s) you want, the VERY least you can do is to conform to this format. The reason why people should ALWAYS include the abstract or if that is unavailable, the first paragraph of the preview, is to allow people to determine whether or not they wish to read the article, and more importantly, it helps people find articles that interest them.

|/color|

The sheer volume of material on this site already is testament to the amount of work done by a few people who have invested their own time, effort and expense to find your articles, if you want their help, show them the respect to which they are entitled.

Catalytic Dehydrogenation of Hydroaromatic Compounds in Benzene. V. Application to Pyrrolidines and Piperidines
Homer. Adkins, Lester G. Lundsted
J. Am. Chem. Soc.
1949, 71 (9), pp 2964–2965
DOI: 10.1021/ja01177a004


Abstract
A catalytic method of dehydrogenating hydroaromatic compounds in benzene in the liquid phase has been evaluated against representative pyrrolidines, indolines, hydrocarbazoles and piperidines...

Influence of degree of sulfonation of BDPP upon enantioselectivity in rhodium-BDPP catalyzed hydrogenation reactions in a two phase system
Cornelis Lensink, Evelien Rijnberg and Johannes G. de Vries
Journal of Molecular Catalysis A: Chemical
1997, Volume 116, Issues 1-2,  Pages 199-207
doi:10.1016/S1381-1169(96)00144-6



Abstract
Asymmetric hydrogenation experiments were carried out with catalysts prepared in situ from [Rh(COD)Cl]2 and 2 eq. of a sulfonated (2S,4S)-bis-2,4-(diphenylphosphino)pentane carrying 0–4 sulfonate groups, in a two phase aqueous organic system. The effect of degree of sulfonation on enantioselectivity was determined in the hydrogenation of one imine and three olefin substrates. In the hydrogenation of the substrates N-benzylacetophenoneimine (2) and dimethyl itaconate (8 ) the monosulfonated ligand 1b was by far superior; hydrogenation using this ligand proceeded with 94% and 28% ee, respectively, whereas use of bis- or trissulfonated ligand gave practically racemic product. In the hydrogenation of N-acetamidocinnamic acid (4) or methyl ester (6) enantioselectivity decreased with degree of sulfonation. The mono sulfonation effect is not due to steric or electronic reasons, nor is an anion effect involved.



----------------------------




Studies on Catalytic Asymmetric Imine Hydrogenation in the Presence of Reverse Micelles:  Enhanced Enantioselectivity due to Surfactant Head Group Coordination
Jillian M. Buriak and John A. Osborn
Organometallics
1996, 15 (14), pp 3161–3169
DOI: 10.1021/om960082t




Abstract
Asymmetric hydrogenation of the imines ArC(Me)NCH2Ph (Ar = C6H5 (2), 4-MeOC6H4 (3)) with Rh[(?)-bdpp](NBD)ClO4 (1) as the catalyst precursor in the presence of reverse AOT micelles results in enhanced enantioselectivity. For 2, the ee in neat methanol is 59% (R), in neat benzene the value is 68% (R), and in benzene in the presence of 0.05 M AOT with w = 5 (5 equiv of water/AOT), the ee increases to 82% (R). For 3, the ee increases from 68% (R) in neat methanol and 80% (R) in neat benzene to 87% (R) in the presence of 0.1 M AOT in benzene. The ee can be further increased to 92% (R) in 96% chemical yield if the reaction is carried out at 4 °C. Substitution of the water with a variety of coadditives such as anisole, 1,2-dimethoxyethane, methanol, and 15-crown-5 to the reverse AOT micelles in benzene also induces large increases in enantioselectivity and chemical yields in the presence of AOT; the highest ee achieved for hydrogenation of 2 with 1 is 87% (R) in quantitative yield in benzene with 0.1 M AOT and 15-crown-5. Since other nonsurfactant sulfonate salts also induce similar enhancements in enantioselectivity, the sulfonate anion, and not the reverse micellar structure, appears to be responsible for the observed increases in ee. 31P NMR and MS studies revealed that the sulfonate anion is bound to the RhI center in a bidentate fashion but is rapidly exchanging on and off the catalyst. The presence of halides, on the other hand, brings about an almost complete inversion of the enantioselectivity for the hydrogenation of 2 using 1. We propose that a change of mechanism of takes place, a dihydride pathway being operative when halide is present and a monohydride pathway in the presence of sulfonates in nonpolar solvents. The coordination of the sulfonate functionality during the enantioselective step(s) also appears to be necessary for the observed increases in enantioselectivity. The fact that sulfonate binding has been shown to play a role in the enantioselectivity of the catalytic hydrogenation has important implications for reactions involving sulfonated phosphine ligands.




-------------------------



Characterization of Route Specific Impurities Found in Methamphetamine Synthesized by the Leuckart and Reductive Amination Methods
Vanitha Kunalan, Niamh Nic Daid, William J. Kerr, Hilary A. S. Buchanan and Allan R. McPherson
Analytical Chemistry
2009, 81 (17), pp 7342–7348
DOI: 10.1021/ac9005588



Abstract
Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of “route specific” impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the “target impurities” recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes.

A Potent and Selective Endogenous Agonist for the µ-Opiate Receptor
Zadina, James E.; Hackler, Laszlo; Ge, Lin-Jun; Kastin, Abba J.
Nature
1997, Volume 386, Issue 6624, pp. 499-502
DOI: 10.1038/386499a0




Abstract
Peptides have been identified in mammalian brain that are considered to be endogenous agonists for the ? (enkephalins) and ? (dynorphins) opiate receptors, but none has been found to have any preference for the µ receptor1-3. Because morphine and other compounds that are clinically useful and open to abuse act primarily at the µ receptor4, it could be important to identify endogenous peptides specific for this site. Here we report the discovery and isolation from brain of such a peptide, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), which has a high affinity (Ki = 360 pM) and selectivity (4,000- and 15,000-fold preference over the ? and ? receptors) for the µ, receptor. This peptide is more effective than the µ-selective analogue DAMGO in vitroand it produces potent and prolonged analgesia in mice. A second peptide, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), which differs by one amino acid, was also isolated. The new peptides have the highest specificity and affinity for the µ receptor  of any endogenous substance so far described and they maybe natural ligands for this receptor.




--------------------------------------




Endomorphin-1 Analogues Containing ?-Proline Are ?-Opioid Receptor Agonists and Display Enhanced Enzymatic Hydrolysis Resistance
Giuliana Cardillo, Luca Gentilucci, Ahmed R. Qasem, Fabio Sgarzi and Santi Spampinato
J. Med. Chem.
2002, 45  (12), pp 2571–2578
DOI: 10.1021/jm011059z



Abstract
In this paper we describe the synthesis and affinity toward the ?-opioid receptor of some tetrapeptides obtained from endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2 (1), by substituting each amino acid in turn with its homologue. The ability to bind ?-opioid receptors depends on the ?-amino acid, and in particular 4, which contains ?-l-Pro, has a KI in the nanomolar range. The peptides 4 and 5 are significantly more resistant to enzymatic hydrolysis than 1. The same compounds, as well as the ?-opioid receptor agonist DAMGO, produced a concentration-dependent inhibition of forskolin-stimulated cyclic AMP formation, thus behaving as ?-opioid agonists. These features suggest that this novel class of endomorphin-1 analogues may represent suitable candidates for the in vivo investigation as potential ?-opioid receptor agonists.

------------------------

Synthesis of no-carrier-added C-11 labeled D- and L-enantiomers of phenylalanine and tyrosine for comparative PET Studies
Andrei R. Studenova, Dava E. Szaldaa and Yu-Shin Ding
Nuclear Medicine and Biology
2003, Volume 30, Issue 1, Pages 39-44
DOI: 10.1016/S0969-8051(02)00349-9



Abstract
The natural amino acids tyrosine (Tyr) and phenylalanine (Phe) were labeled with carbon-11 via a modified Bucherer-Strecker synthesis. A rapid reaction of the sodium bisulfite adduct of the aldehyde precursor with ammonia provided the precursor for radiosynthesis. [11C]Cyanide displacement followed by base hydrolysis afforded the corresponding 11C-labeled amino acids. The purification and chiral separation were simply achieved by using a combination of solid-phase extraction and chiral HPLC to afford individual enantiomers of each amino acid. The decay corrected radiochemical yields for each of the enantiomers were 12–16% with respect to the [11C]cyanide after 40–45 min of radiosynthesis. Radiochemical purity of the products was >97% (typically >99%), enantiomeric excess was >98% with the specific radioactivity 2–3 Ci/?mol at the end of bombardment. Because of its simplicity and wide applicability, the described procedure could be the method of choice to produce [11C]amino acids for PET studies.



--------------------------



New Syntheses of Aromatic Acid Chlorides from Trichloromethylarenes. 1. Reaction with Sulfur Dioxide
Christian S. Rondestvedt
J. Org. Chem.,
1976, 41 (22), pp 3569–3574
DOI: 10.1021/jo00884a017



Abstract
Trichloromethylarenes (benzotrichlorides) react with sulfur dioxide above ~150C to yield aroyl chlorides and thionyl chloride in high yields. 1,3-Bis(trichloromethyl)benzene reacts especially well to yield isophthaloyl chloride. The reaction proceeds at a much lower temperature in the presence of antimony pentachloride or other Lewis acids, although Friedel-Crafts side reactions reduce the yield of aroyl chloride unless the ring bears strongly electron-attracting substituents. Both thermal and catalyzed reactions are interpreted in terms of dichlorobenzyl cation intermediate, although an alternative radical mechanism was also demonstrated by adding di-tert-butyl peroxide.

Oxazolines. Their preparation, reactions, and applications
John A. Frump
Chem. Rev.
1971, 71 (5), pp 483–505
DOI: 10.1021/cr60273a003[/color]


----------------------------------


The Chemistry of the Oxazolines.
Richard H. Wiley, Leonard L. Bennett
Chem. Rev.
1949, 44 (3), pp 447–476
DOI: 10.1021/cr60139a002

Preparation of p-[(S)( - )-2-phthalimidopropionyl] polystyrene
Z. Janovi, D. Fle
Journal of Polymer Science Part A-1: Polymer Chemistry
2003, Volume 6(7),  pp.1871-1876
DOI: 10.1002/pol.1968.150060709


Abstract
Samples of atactic and isotactic polystyrene were acylated with N-phthaloyl-L-alanyl chloride under the conditions of Friedel-Crafts reaction. The degree of acylation was strongly dependent on molecular weight, but not on the tacticity of polystyrene. Similarly the specific rotation of acylated polymers was not influenced by the structure of the polymer chain.