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Acute pulmonary embolism may cause right heart failure due to increased pulmonary vascular resistance and arterial hypoxemia. Effective vasodilator therapy of the pulmonary hypertension is highly needed. Therefore, we investigated the effects of a newly developed effective pulmonary vasodilator, the organic mononitrites of 1,2‐propanediol (PDNO), in a rabbit model of acute pulmonary embolism. In anesthetized and ventilated rabbits, systemic and pulmonary hemodynamics, exhaled nitric oxide (NO), plasma nitrite concentration, and blood gases were monitored. First, dose–response experiments with intravenous and left heart ventricle infusions of PDNO and inorganic nitrite were done in naive animals and in pulmonary hypertension induced by a thromboxane A2 analogue. Second, acute pulmonary embolism was induced and either PDNO or placebo were administered intravenously within 20 minutes and evaluated within 1 hour after pulmonary embolization. PDNO intravenously, in contrast to inorganic nitrite intravenously, increased exhaled NO and counteracted pulmonary hypertension and vasodilated the systemic circulation, dose‐dependently, thereby showing efficient NO donation. Pulmonary embolization induced pulmonary hypertension and gas exchange disturbances. PDNO significantly decreased and normalized pulmonary vascular resistance and the right ventricle rate‐pressure product, without causing tolerance, with no significant side effects on the systemic circulation, nor on blood‐gas values or on methemoglobin formation. In conclusion, PDNO is a NO donor and an efficient vasodilator in the pulmonary circulation. Treatment with this or similar organic nitrites intravenously may be a future option to avoid right heart failure in life‐threatening acute pulmonary embolism.

We reported the case of 69-year-old man who was discovered dead at a friend's home. 3-Methylmethcathinone (3-MMC) and poppers (alkyl nitrites) were found at the scene by the police. Autopsy specimens including peripheral and cardiac blood, urine, gastric content, bile and hair were sent to our laboratory to document a possible death involving abuse of drugs. Routine toxicological analysis was performed with gas chromatography with flame ionization detection (GC-FID), high performance liquid chromatography-diode array detection (HPLC-DAD), headspace gas chromatography-mass spectrometry (HS-GC-MS), gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)-MS. After liquid-liquid extraction at alkaline pH, 3-MMC was identified with GC-MS (to allow the discrimination with 4-MMC) and quantified with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-MS with the two following transitions: m/z 178.1 > 160 and 178.1 > 144.9. Gamma-hydroxybutyric acid (GHB) was analyzed by GC-MS for fluids and GC-MS-MS for hair. Toxicological analysis in peripheral blood revealed the presence of 3-MMC (0.33 mg/L), pseudoephedrine (0.03 mg/L) and GHB (576 mg/L). These molecules have also been found in other post-mortem fluids. Furthermore, testing for "poppers" by HS-GC-MS was negative. Hair analysis, without segmentation, demonstrated the presence of 3-MMC (206.7 ng/mg), pseudoephedrine (0.16 ng/mg) and GHB (96.3 ng/mg) and suggested a repeated consumption of these substances. However, one cannot exclude contamination by sweat during the agony period. Toxicological post-mortem results suggest a fatal combination of 3-MMC and GHB. Despite his age, the decedent was known to abuse drugs.

An efficient, one-pot approach has been described for the synthesis of 3,5-disubstituted isoxazoles from substituted aldoximes (mixture of E and Z) and alkynes, using alkyl nitrites under conventional heating conditions. The key nitrile oxide intermediates that are required for the synthesis of isoxazoles are formed by treatment of substituted aldoxime with either tert-butyl nitrite or isoamyl nitrite. The generated nitrile oxides underwent in situ [3+2] dipolar cycloaddition to the substituted alkynes to give 3,5-disubstituted isoxazoles regioselectively in high to excellent yields. The developed synthetic methodology was applied for the synthesis of a previously reported potent hDGAT1 inhibitor.

We first characterize the dissociation pathways of BrCH2CH2ONO, a substituted alkyl nitrite, upon photoexcitation at 193 nm under collision-free conditions, in a crossed laser-molecular beam scattering apparatus using vacuum ultraviolet photoionization detection. Three primary photodissociation pathways occur: photoelimination of HNO, leading to the products HNO + BrCH2CHO; C-Br bond photofission, leading to Br + CH2CH2ONO; and O-NO bond photofission, leading to NO + BrCH2CH2O. The data show that alkyl nitrites can eliminate HNO via a unimolecular mechanism in addition to the commonly accepted bulk disproportionation mechanism. Some of the products from the primary photodissociation pathways are highly vibrationally excited, so we then probe the product branching from the unimolecular dissociation of these unstable intermediates. Notably, the vibrationally excited CH2CH2ONO radicals undergo two channels predicted by statistical transition-state theory, and an additional non-intrinsic reaction coordinate channel, HNO elimination. CH2CH2ONO is formed with high rotational energy; by employing rotational models based on conservation of angular momentum, we predict, and verify experimentally, the kinetic energies of stable CH2CH2ONO radicals and the angular distribution of dissociation products. The major dissociation pathway of CH2CH2ONO is NO2 + ethene, and some of the NO2 is formed with sufficient internal energy to undergo further photodissociation. Nascent BrCH2CHO and CH2Br are also photodissociated upon absorption of a second 193 nm photon; we derive the kinetic energy release of these dissociations based on our data, noting similarities to the analogous photodissociation of ClCH2CHO and CH2Cl.

Although alkyl nitrites are used as recreational drugs, there is only little research data regarding their effects on the central nervous system including their neurotoxicity. This study investigated the neurotoxicity of three representative alkyl nitrites (isobutyl nitrite, isoamyl nitrite, and butyl nitrite), and whether it affected learning/memory function and motor coordination in rodents. Morris water maze test was performed in mice after administrating the mice with varying doses of the substances in two different injection schedules of memory acquisition and memory retention. A rota-rod test was then performed in rats. All tested alkyl nitrites lowered the rodents' capacity for learning and memory, as assessed by both the acquisition and retention tests. The results of the rota-rod test showed that isobutyl nitrite in particular impaired motor coordination in chronically treated rats. The mice chronically injected with isoamyl nitrite also showed impaired function, while butyl nitrite had no significant effect. The results of the water maze test suggest that alkyl nitrites may impair learning and memory. Additionally, isoamyl nitrite affected the rodents' motor coordination ability. Collectively, our findings suggest that alkyl nitrites may induce neurotoxicity, especially on the aspect of learning and memory function.

We present a DC slice imaging study of the decomposition of C2, C3 and C4 nitroalkanes and alkyl nitrites, focusing on the NO elimination channel, possibly a minor pathway. Infrared multiphoton dissociation (IRMPD) is used to induce dissociation on the ground electronic state under collisionless conditions. The channels that produced NO as a product were studied and compared among the target molecules to gain a better understanding of the isomerization of the nitroalkanes prior to dissociation. Trends in the total translational energy and NO rotational temperatures obtained from the images are discussed.

Therapies - In Press.Proof corrected by the author Available online since lundi 5 decembre 2016

The thermal dissociations of three alkyl nitrites (C 3 H 7 ONO, n -C 4 H 9 ONO, and i -C 4 H 9 ONO) have been studied in a diaphragmless shock tube by laser schlieren densitometry over 700 T P k 1 , were obtained with an uncertainty of 30%. Rice–Ramsperger–Kassel–Marcus/Master Equation (RRKM/ME) calculations for dissociation of the nitrites were performed and provide excellent simulations of the experimental results. The high-pressure limit rate coefficients from the RRKM/ME calculations are: k 1 , C 3 H 7 ONO = ( 5.69 ± 1.71 ) × 10 21 T − 1.60 e x p ( − 21458 / T ) s − 1 ; k 1 , n − C 4 H 9 ONO = ( 9.91 ± 2.97 ) × 10 21 T − 1.59 e x p ( − 21588 / T ) s − 1 ; k 1 , i − C 4 H 9 ONO = ( 3.92 ± 1.18 ) × 10 21 T − 1.58 e x p ( − 21162 / T ) s − 1 . At the low temperatures of this work, the alkyl radicals are thermally stable and thus their recombination reactions were also studied. The recombination rate coefficients for ethyl, n- propyl and i- propyl radicals (uncertainties of 50%) are in excellent agreement with literature values, particularly recent theoretical results, and extend the range of experiments to higher temperatures.

Chitosan has received substantial attention as a biomaterial due to its unique properties. It has become increasingly common to derivatize chitosan to produce nitric oxide (NO)-releasing materials that exert various therapeutic effects through the action of NO. It is generally the case that these NO-releasing polymers are prepared by exposure to high-pressure NO or nitrosating agents like nitrous acid (HNO2) or alkyl nitrites (RONO). In our study, mass spectrometry and spectroscopic methods demonstrate that both monomeric and oligomeric glucosamine experience chemical alteration after exposure to HNO2-based nitrosating conditions from the literature. In polymeric chitosan, HNO2-based nitrosating conditions were found to induce degradation through the formation of 2,5-anhydro- d -mannose and oligosaccharides. In contrast, the RONO tert-butyl nitrite and high-pressure NO were not found to significantly degrade or otherwise alter the structure of glucosamine or its oligomers, supporting the suitability of these approaches.

History, chemical profile There is a virtually infinite number of volatile substances of abuse that can be inhaled: glue, gasoline, spray paint, household products. These substances all have different effects. Nitrous oxide, known as whippets, act on NO receptors. They induce smooth muscle relaxation and hypotension. Alkyl Nitrites, known as poppers, are NO receptor agonists and have similar effect to whippets. They were first synthetized by Ballard in 1844 and used in angina. How does the drug present, how is it consumed? There are all kind of methods to use inhalants: sniffing, bagging, or huffing Poppers and whippets are liquid substances usually packaged in small bottles. They are inhaled by approaching the opened bottle to a nostril. Context of using and desired effect Poppers and whippets became popular in the gay community in the 1970s and more generally during the sexual liberation movement. They induce a brief moment of euphoria, intense excitement, and decupled interest for the sexual partner. Poppers’ smooth muscle relaxation effect facilitate anal sex.

In this contribution we use computational tools to investigate the reaction of alcohol substrates with reactive nitrogen oxide species such as N2O3 and N2O4, leading to the formation of alkyl nitrites. These nitrites are interesting intermediates which can be processed to various valuable chemicals such as ketones/aldehydes and dimethyl oxalate while regenerating NO x . As such, NO x is used as an oxidation mediator, converting alcohol substrates to more reactive nitrites which can be selectively converted to more desired compounds, closing a catalytic cycle in NO x species.

Hydroxy fatty acids (HFAs) are high-added-value compounds, which are incorporated in polymers, lubricants, emulsifiers and stabilizers and have potential medicinal use. In nature, HFAs are regio-specifically synthesized by several enzymes, including P450 monooxygenases, lipoxygenases, hydratases, 12-hydroxylases, and diol synthases. The growing demand for HFAs warrants the development of simple and efficient analytical methods that enable high-throughput detection of the hydroxylated product in the presence of its unsaturated precursor. Herein a novel high-throughput assay for the detection of alcohols is described using oleate hydratase (OHase, EC 4.2.1.53) from Elizabethkingia meningoseptica as the model enzyme. The developed assay is based on the selective spectrophotometric detection of alkyl nitrites formed upon the reaction between the hydroxyl group and nitrous acid. The assay proved to discriminate between unsaturated fatty acids as well as small cyclic and acyclic unsaturated alkenes and their corresponding alcohols. Lower detection limits were 1.5-3 mM with excellent Z'-factors. Enzymatic reactions using OHase with oleic acid resulted in somewhat lower Z-factors for various enzyme preparations. This small scale assay can enable fast discovery of new microorganisms or improved enzymes from mutant libraries and will be useful for biocatalytic strategies involving fatty acid (de)hydrating enzymes.

In recent years, many analogs of narcotics have been widely distributed as easily available psychotropic substances and have become a serious problem in Japan. To counter the spread of these non-controlled substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category; Designated Substances in order to more strictly control these substances. In April 2007, 31 compounds and 1 plant were first controlled as Designated Substances. Before 2007, the major compounds distributed in the Japanese illegal drug market were tryptamines, phenethylamines and piperazines. Alkyl nitrites, such as isobutyl nitrite and isopentyl nitrite, were also widely distributed. After they were listed as Narcotics or Designated Substances in 2007, these compounds, especially the tryptamines, quickly disappeared from the market. In their place, cathinone derivatives have been widely distributed, as well as different phenethylamines and piperazines. Additionally, in recent years, new herbal products containing synthetic cannabinoids have appeared globally. As at July 2012, 78 substances (including 1 plant; Salvia divinorum) were listed in the category of Designated Substances. They were 13 tryptamines, 17 phenethylamines, 11 cathinones, 4 piperazines, 23 synthetic cannabinoids, 6 alkyl nitrites, 3 other compounds and 1 plant. In this review, we show our survey of the spread of new designer drugs in Japan, focusing especially on synthetic cannabinoids and cathinone derivatives. Also, the prevalence and legal status of these substances in other countries will be presented.

An efficient metal-free phosphorylation process based on a Sandmeyer-type transformation with arylamines as the starting materials is developed. The transformation proceeds smoothly at room temperature without the exclusion of moisture or air. This phosphorylation reaction tolerates a wide range of functional groups and affords the phosphorylation products in moderate to good yields, thus providing a valuable method for the formation of aromatic carbon-phosphorus bonds.

The abuse of alkyl nitrites is common among adolescents and young adults worldwide. However, the information regarding the effects of alkyl nitrites on the central nervous system and the associated psychological abuse potential is scarce. The abuse potential of 3 representative alkyl nitrites - isobutyl nitrite, isoamyl nitrite, and butyl nitrite - was evaluated in mice using conditioned place preference tests with an unbiased method. The dopamine levels released by synaptosomes extracted from the striatal region were measured using high performance liquid chromatography. Mice treated with the test substances (50mg/kg, i.p.) exhibited a significantly increased drug-paired place preference. Moreover, greater levels of dopamine were released by striatal region synaptosomes in response to isobutyl nitrite treatment in mice. Thus, our findings suggest that alkyl nitrites could lead to psychological dependence and dopaminergic effects. Furthermore, these results provide scientific evidence to support the regulation of alkyl nitrites as psychoactive substances in the future.

Alkyl nitrites have been used previously to produce alkoxy radicals, which are important intermediates in the oxidation of alkanes in atmospheric and combustion processes. Substituted alkoxy radicals, particulary hydroxyalkoxy radicals, are also important intermediates in the atmospheric oxidation of alkenes and combustion of alcohols. In order to produce substituted alkoxy radicals we have photolyzed at 351 nm substituted alkyl nitrites, XCH(2)CH(2)ONO (X = F, Cl, Br, OH). Using laser-induced fluorescence only in the case of X = F do we observe the spectrum of substituted alkoxy radical, XCH(2)CH(2)O; but we always observe the electronic transitions of formaldehyde, HCHO, and vinoxy radical, CH(2)CHO. HCHO can be formed by the dissociation of XCH(2)CH(2)O in its ground state as the barrier to C-C bond dissociation is less than the photon energy remaining after O-NO bond breakage. However, the barrier along the reaction path directly leading from XCH(2)CH(2)O to CH(2)CHO + HX is much higher than the available energy remaining after O-NO bond breakage. A roaming mechanism, involving a frustrated dissociation of X followed by HX extraction, might explain the apparent paradox. Under the conditions of our observations vinoxy retains considerable vibrational excitation but the observed rotational temperatures of both HCHO and CH(2)CHO are ≲7 K.

The oxidation of primary and secondary benzylic alcohols was achieved by using tert-butyl nitrite (t-BuONO) as a stoichiometric oxidant. Various substrates were effectively converted into the corresponding ketones or aldehydes in good to excellent yields. The reaction presumably proceeded by a nitrosyl exchange and a subsequent thermal decomposition of benzylic nitrites. This process would realize an oxidation of alcohols with oxygen in theory by combining with a reproduction of alkyl nitrites from NO and alcohols under an O2 atmosphere. In addition, almost pure oxidized products were readily obtained by simple evaporation of the reaction mixtures since t-BuONO produced only volatile side products.

Alkyl nitrites photolyze in air to yield alkoxy radicals and NO which, through secondary reactions, generate OH radicals. This photochemistry is important in the atmosphere and in laboratory studies where nitrites are often used as a source of OH. The overall quantum yield for hydroxyl radical formation from irradiation of isopropyl nitrite (i-C(3)H(7)ONO) between 300 and 425 nm in 1 atm air at 296 ± 2 K is reported for the first time. The OH radical was scavenged by reaction with CF(3)CF═CF(2) and the formation of CF(3)CFO and CF(2)O monitored as a function of time using Fourier transform infrared spectrometry. The quantum yield was found to be 0.54 ± 0.07 (2σ) and is independent of whether or not NO was added (up to 3 × 10(14) molecules cm(-3)) prior to photolysis to increase NO concentrations above those due to the photolysis of the nitrite. Ultraviolet-visible and infrared cross sections of i-C(3)H(7)ONO are also reported. These data on the OH quantum yields as well as the UV-visible and infrared cross sections for isopropyl nitrite are critical for quantitatively interpreting the results of laboratory studies where i-C(3)H(7)ONO is employed as an OH source as well as for assessing the role of alkyl nitrites in the chemistry of the troposphere.

The kinetic characteristics of the oxidation of normal butane were investigated in the temperature region of 220-270° C. The reaction is autocatalytic, it is accelerated by increase of pressure, temperature and the concentration of butane, while oxygen retards the velocity of reaction. The Semenoff relation Δp = Aeφtis found to hold in the above-mentioned temperature region. The state of the walls exerts great influence on the reaction velocity: a covering of KCl on the walls leads to a retardation of the reaction, mainly by a lowering of the value of φ. Indications were found that it is also possible to poison the walls in such a way that the value of A is also decreased. It is possible to increase A by the addition of small amounts of foreign substances. Very active among such substances are alkyl nitrites and nitrates, as well as diethyl ether and n-butyl aldehyde. From the analysis of the reaction products it was found that at high concentrations of the combustible substance considerable reaction already occurs during the induction period. It was found that a sudden acceleration of the increase in pressure occurring at these concentrations could be correlated with the maximum of the peroxide concentration.

Monomeric primary and secondary nitrosoalkanes have been generated from the trans-dimers by heating in solution. The monomers are photochemically and thermally far more reactive than the dimers. They are isomerized to oximes in 90% yield thermally. Photolysis of nitrosocyclohexane with red light leads to the oxime in 60% yield. Photolysis in the presence of oxygen gives nitrocyclohexane as the main product (85%), together with a small amount of cyclohexyl nitrate. Considerable amounts of cyclohexanol are formed by oxidation of the solvent cyclohexane, presumably via a nitroxide-type intermediate. When t-butyl nitrite is photolyzed with light in the region of 400 nm and in the presence of oxygen in CFCl3, t-butyl nitrate is produced in 90% yield, by the action of intermediary NO and NO2 radicals.

Density functional theory (DFT) based calculations are performed on a series of alkyl nitrites and nitroalkanes representing large-scale primary, secondary, and tertiary nitro compounds and their radicals resulting from the loss of their skeletal hydrogen atoms. Geometries, vibration frequencies, and thermochemical properties [S°(T) and C°p(T) (10 K ⩽ T ⩽ 5000 K)] are calculated at the B3LYP/6-31G(d,p) DFT level. ΔfH°298 values are from B3LYP/6-31G(d,p), B3LYP/6-31+G(2d,2p), and the composite CBS-QB3 levels. Potential energy barriers for the internal rotations have been computed at the B3LYP/6-31G(d,p) level of theory, and the lower barrier contributions are incorporated into entropy and heat capacity data. The standard enthalpies of formation at 298 K are evaluated using isodesmic reaction schemes with several work reactions for each species. Recommended values derived from the most stable conformers of respective nitro- and nitrite isomers include −30.57 and −28.44 kcal mol−1 for n-propane-, −33.89 and −32.32 kcal mol−1 for iso-propane-, −42.78 and −41.36 kcal mol−1 for tert-butane-nitro compounds and nitrites, respectively. Entropy and heat capacity values are also reported for the lower homologues: nitromethane, nitroethane, and corresponding nitrites. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 181–199, 2010

The mechanistic aspects of the photo induced reactions of gaseous amyl nitrite have been investigated using ab initio calculations. We show that the C 5 H 11 O–NO bond dissociation mechanism is different on the S 1 and S 2 surfaces, respectively. The subsequent conformational changes in the ground state 1-pentoxy radical involves several barriers. Interestingly, we show that the intramolecular 1,5-H transfer in the 1-pentoxy radical proceeds in the opposite direction on the S 1 state compared to the S 0 reaction. Moreover, the results show that the excited state reaction of the alkoxy radical may be a proton transfer that proceeds on a repulsive surface.

A method for the safe and reliable iododeamination of aromatic and heteroaromatic amines under copper-free conditions is described and its scope is evaluated.

We review studies of the effects of low ambient ozone concentrations on morbidity that found a negative coefficient for ozone concentration. We call this a Paradoxical Ozone Association (POA). All studies were in regions with methyl ether in gasoline. All but one study carefully controlled for the effects of other criterion pollutants, so the phenomenon cannot be attributed to them. One was in southern California in mid-summer when ozone levels are highest.Because ozone is created by sunlight, the most plausible explanation for a POA would be an ambient pollutant that is rapidly destroyed by sunlight, such as methyl nitrite (MN). A previously published model of engine exhaust chemistry suggested methyl ether in the fuel will create MN in the exhaust. MN is known to be highly toxic, and closely related alkyl nitrites are known to induce respiratory sensitivity in humans. Support for the interpretation comes from many studies, including three linking asthma symptoms to methyl tertiary butyl ether (MTBE) and the observation that a POA has not been seen in regions without ether in gasoline. We also note that studies in southern California show a historical trend from more significant to less significant ozone-health associations. The timing of those changes is consistent with the known timing of the introduction of gasoline oxygenated with MTBE in that region. Keywords: Asthma, Biodiesel, California, DME, MTBE, Nocturnal, Nitrogenous compounds, Japan, Ozone, TAME, Cough

Raman and infrared spectra of n-butyl, isobutyl, sec-butyl and tert-butyl nitrite are reported. Density functional theory and Møeller-Plesset calculations with 6-31G* and 6-311G* basis sets were used to determine ground state molecular geometries and vibrational frequencies of these compounds. Calculations and spectral data of these molecules were used to perform partial vibrational mode assignments for the observed transitions. In agreement with previous investigations of alkyl nitrites, cis and trans rotational conformers of n-butyl, isobutyl and sec-butyl nitrite were observed in the gas phase infrared spectra and the condensed phase Raman and infrared spectra. Among the several predicted geometries of these compounds, the cis-trans geometry (cis with respect to the C-O-N=O dihedral angle and trans with respect to the C-C-O-N dihedral) was calculated to be the most stable conformer of n-butyl and isobutyl nitrite, while the cis-gauche conformer was found to be the most stable geometry of sec-butyl nitrite. The cis-type structures of these three molecules are favored due to formation of a pseudo hydrogen bond between the nitrite group and the alpha-carbon hydrogen atoms. Hindrance with the alkyl moiety, however, causes the trans conformer (trans with respect to the C-O-N=O dihedral) of tert-butyl nitrite to lie lower than its cis conformer, a result that was supported by our spectroscopic measurements. The characteristic N=O stretch frequency for the trans conformers of all the compounds examined was observed to decrease with increasing branching at the alpha-carbon, while the same mode for the cis conformers shows no change among the primary and secondary nitrites. Evidence is also provided that suggests that the relative number of cis conformers to trans conformers decreases as the alpha-carbon branching increases.

The photodissociation of alkyl nitrites series (RONO) in gaseous state were studied using density functional theory with Amsterdam Density Functional program (ADF2000) and quantum chemical molecular dynamical method by “Colors-Excite” code. The different dissociative phenomena have been explained by this investigation. Alkyl nitrites were shifted to their excited states by capturing the light energy and the bonds of O–N (RO–NO) were broken. A two-step reaction occurred for methyl nitrite (THN) to yield the diverse products, such as RO radical, NO and HNO, whereas only one-step reaction occurred for tert -butyl nitrite (TBN). The consistent results in theoretical calculation and experiment, including geometrical structures and excitation energies, demonstrated the good performances of “Colors-Excite”.

Condensed-phase alkoxy (RO) radicals can undergo unimolecular (e.g., intramolecular H-atom abstraction) reactions as well as bimolecular (intermolecular H-atom abstraction) reactions, though the competition between these two channels is not well constrained. Here we examine this branching, by generating RO radicals from the photolysis of a large alkyl nitrite (C20H41ONO) in hexanes, and nebulizing the mixture into an aerosol mass spectrometer for analysis. Product ions associated with unimolecular (isomerization) reactions were observed to increase upon photolysis. However, no formation of the C20 alcohol (C20H41OH, the expected product from RO + RH reactions) was observed, suggesting that bimolecular reactions are at most a minor channel for this condensed-phase system (involving saturated hydrocarbons). This result, combined with previous studies of condensed-phase RO radicals carried out at higher concentrations, suggests that when 1,5-H-atom abstraction reactions are facile (i.e., in which a 1,5-H-atom shift from a secondary or tertiary carbon can occur), this channel will dominate over bimolecular reactions.

Although aliphatic nitro compounds, aliphatic nitrates, and aliphatic nitrites have several features in common (nitrogen-oxygen grouping, explosiveness, methemoglobin formation), there are significant differences in their toxic effects. Some of their attributes are summarized. The esters of nitric and nitrous acid, whose nitrogen is linked to carbon through oxygen, are very similar in their pharmacological effects. Both produce methemoglobinemia and vascular dilatation with hypotension and headache. These effects are transient. None of the series has appreciable irritant properties. Pathological changes occur in animals only after high levels of exposure and are generally nonspecific and reversible. The nitric acid esters of the monofunctional and lower polyfunctional alcohols are absorbed through the skin. Information is not available on the skin absorption of alkyl nitrites. Members of both groups are well absorbed from the mucous membranes and lungs. Heinz body formation has been observed with the nitrates but not with the nitrites. Nitro compounds, like nitrates and nitrites, cause methemoglobinemia in animals. Heinz body formation parallels this activity within the series. Although some members are metabolized to nitrate and nitrite, there is no significant effect on blood pressure or respiration. As with the lower nitrates and nitrites, anesthetic symptoms are observed in animals during acute exposures, but these occur late. The prominent effect is irritation of the skin, mucous membranes, and respiratory tract. This is most marked with chlorinated nitroparaffins and nitroolefins. In addition to respiratory tract injury, cellular damage may be observed in the liver and kidneys. Skin absorption is negligible except for the nitroolefins. The nitramines have entirely different activity. RDX is a convulsant for humans and animals. Skin absorption, irritation, vasodilatation, methemoglobin formation, and permanent pathological damage are either insignificant or absent after repeated doses. Transient illness has been associated with the industrial use or manufacture of these materials, but fatalities and chronic intoxication have been uncommon. Some members of each group present extremely high fire and explosion hazards. Keywords: Aliphatic nitro compounds; Aliphatic nitrates; Aliphatic nitrites; Nitroolefins; Alkyl nitrites

A method for the synthesis of peroxynitrite is described. It involves nitrosation of H2O2 at pH> or = 12.5 by isoamyl or butyl nitrite in mixed solvents of isopropyl alcohol (IPA) and water at 25+/-1 degrees C. Maximum yields of peroxynitrite are obtained after 15 min of incubation at IPA concentrations of 30-70% (v/v). The solutions of peroxynitrite are processed for removal of IPA and isoamyl alcohol by solvent extraction. Unreacted H2O2 is removed by catalytic decomposition on granular MnO(2). The post processed solutions of peroxynitrite are useful in several chemical and biochemical investigations where bolus additions are required. The method as reported is amenable for large scale synthesis as it involves sequential mixing of solvents (water and IPA) to alkali followed by the addition of H2O2 and alkyl nitrite.

Halohydrin dehalogenase obtained from Agrobacterium radiobacter AD1, has been tested for the nitrite-mediated ring opening of epoxides. This reaction mainly leads to the formation of unstable hydroxynitrite ester intermediates, which can be further hydrolyzed to the corresponding diols. This conversion proceeds with high enantioselectivity and high regioselectivity towards styrene oxide derivatives. It has been concluded that halohydrin dehalogenase can serve as an attractive alternative to epoxide hydrolases in the preparation of enantiopure epoxides by kinetic resolution.

Alcohols in acetonitrile are converted into alkyl nitrates, nitrites, or thiocyanates by the action of triphenylphosphine and trichloroisocyanuric acid along with silver nitrate, silver nitrite, or sodium thiocyanate, respectively.

Volatile alkyl nitrites have been used during the past decades for "recreational purposes," and for intensifying sexual experience. Their use has been associated with methemoglobinemia and hemolysis. We report three patients who presented over the past year with acute hemolysis after inhalation of butyl nitrite, two of them had glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Some conditions of storage have been tested for stability of n- butyl alcohol, isobutyl alcohol and isoamyl alcohol as decomposition products of alkyl nitrites in human whole blood samples. The above three alkyl alcohols (1μg/ml each) were spiked to whole blood, and kept at room temperature or at 4℃ for various intervals without any addition of preservatives. The alkyl alcohols were measured by the cryogenic oven trapping gas chromatography. At room temperature, the alkyl alcohols gradually decreased for 7 days; but the decreased rates were only 10 - 25%. At 4℃, the compounds were almost stable for at least 14 days. There were no postmortem production for each alkyl alcohol. Our results support the idea that the decomposition product alkyl alcohols can be used for detection of alkyl nitrite abuse.

Allyl nitrite, ONOCH2CHCH2, can exist in conformations which include syn (S) and anti (A) configurations of ONOC, anti or gauche (G) configurations of NOCC, and syn or skew (Sk) configurations of OCCC. Four of them have been observed and characterized by their microwave spectra and quantum chemical calculations to have AGSk′ (0.0 kcal/mol), AGSk (0.2(2) kcal/mol), SASk (0.2(2) kcal/mol), and SAS (0.9(2) kcal/mol) configurations about the three successive dihedral angles. All four are observed in microwave studies of the vapor at 300 and 200 K and the first three are seen in pulsed-jet beams. The SAS form apparently relaxes to the SASk conformer during expansion in the pulsed-jet. Quantum chemical calculations reveal that the two possible conformers with anti–anti configurations of the ONOCC fragment, AAS and AASk, are transition states, unstable configurations, or of marginal stability, consistent with structures observed in this and other previously studied alkyl nitrites. The remaining four possible conformers are predicted to have relative energies within 1 kcal/mol of the observed conformers but were not observed experimentally. Chirality 14:232–240, 2002. © 2002 Wiley-Liss, Inc.

We review some of the work that we have been doing in the field of chemical kinetics on the reactivity of alkyl nitrites in microorganized media. For comparative purposes, the reactivity of alkyl nitrites in water, organic solvents, aqueous g -cyclodextrin solutions and aqueous micellar solutions is reviewed. After a brief description of common properties of alkyl nitrites and of microorganized media, we report kinetic studies on the reactivity of alkyl nitrites. The emphasis is on three important reactions undergone by these reagents in solution, namely acid-catalysed hydrolysis, base-catalysed hydrolysis and NO-transfer reactions, mainly to amines to produce nitroso compounds. The principal features observed through the experimental study of these reactions allow reaction mechanisms in each reaction medium to be prepared; these give information on the constitution of the transition state and its energy characteristics, the presence of possible intermediates, the effects of structural variation on rate a...

A simple and sensitive method for the determination of liquid methanol and ethanol at trace levels by an alkyl nitrite formation reaction has been established. Alcohol was allowed to react with nitrous acid, which was yielded from sulfuric acid and sodium nitrite in the solution, to form the corresponding alkyl nitrite in the hexane organic phase. Alkyl nitrites in hexane were analyzed by a gas chromatograph with an electron capture detector (GC-ECD). The detection limits, which were determined at a signal-to-noise ratio of 3, were 1.1 and 0.7 micrograms/L for methanol and ethanol, respectively, by 1 microL injection. The relative standard deviations for n = 8 were 4.0 and 3.3% for methanol and ethanol, respectively. The method was applied to determine the alcohol concentration in a rice paddy, pond water, tap water, and well water. Those aqueous samples were also spiked with standard alcohols; the average recoveries of spiked methanol and ethanol were 98 and 91% with relative standard deviations of 6.1 and 4.0%, respectively.

The “donor-induced” generation of nitrosonium cation in acidified solutions of alkyl nitrites in dichloromethane is demonstrated spectroscopically. Electron-rich organic molecules, including polymethylbenzenes and thioethers, affect the donor-induced release of nitrosonium as the corresponding electron donor–acceptor complex [donor, NO+]. These complexes are spectrally identified using a combination of UV–vis and IR spectroscopy. The almost quantitative formation of the [donor, NO+] EDA complex with hexamethylbenzene and butyl sulfide as donors is verified with UV–vis spectroscopy.

A one-step synthesis of adsorbed alkoxides from alkyl nitrites dosed on Cu(100) is illustrated using methyl nitrite (CH3ONO) to form methoxide (CH3O) and tert-butyl nitrite (t-C4H9ONO) to form tert-butoxide (t-C4H9O). Compared with an alternative, dosing CH3OH on an O-covered Cu surface, only minor differences in the concentration and local chemical environment of CH3O are evident. The potential energy profiles associated with the two synthesis methods are contrasted, and the key role played by the weak RO−NO bond is emphasized.

This paper presents a flow determination method for low molecular weight alcohols (methanol, ethanol) in the gas phase using the nitrite formation reaction, which was developed from an earlier method using a glass bottle. In this method, the ambient air and nitrogen dioxide (1,000 ppmv) were allowed to continuously flow in a glass tube, which had been filled with 10 g of Pyrex glass beads. The flow rates of the ambient air and nitrogen dioxide were 30 and 20 cm3/min, respectively. The gas-phase alkyl nitrites produced by the dark reaction of atmospheric alcohols and nitrogen dioxide on the Pyrex glass beads were then analyzed by gas chromatography with an electron capture detector. The alcohol concentrations of the samples were calculated using a calibrated conversion factor for each alcohol to its nitrite. The detection limits for the methanol and ethanol are 0.7 and 0.5 ppbv, respectively. This flow method was used to determine the atmospheric alcohol concentrations and was found to have the advantages of a short sampling time and simple quantitative procedure compared with the previously reported method (glass bottle method). The feasibility of this method was also established.

Ascorbate reacts with S-nitrosothiols generally, in the pH range 3–13 by way of two distinct pathways, (a) at low [ascorbate], typically below ≈1 × 10−4 mol dm−3 which leads to the formation of NO and the disulfide, and (b) at higher [ascorbate] when the products are the thiol and NO. Reaction (a) is Cu2+-dependent, and is completely cut out in the presence of EDTA, whereas reaction (b) is totally independent of [Cu2+] and takes place readily whether EDTA is present or not. For S-nitrosoglutathione (GSNO) the two reactions can be made quite separate, although for some reactants the two reactions overlap. In reaction (a), ascorbate acts as a reducing agent, generating Cu+ from Cu2+, which in turn reacts with RSNO forming initially NO, Cu2+ and RS−. The latter can then play the role of reducing agent for Cu2+, leading to disulfide formation. Ascorbate will initiate reaction when the free thiolate has initially been reduced to a very low level by the synthesis of RSNO from a large excess of nitrous acid over the thiol. Reaction (b) is interpreted in terms of nucleophilic attack by ascorbate at the nitroso-nitrogen atom, leading to thiol and O-nitrosoascorbate which breaks up, by a free-radical pathway, to give dehydroascorbic acid and NO. A similar pathway is the accepted mechanism in the literature for the nitrosation of ascorbate by nitrous acid and alkyl nitrites. The rate constant for the Cu2+ -independent pathway increases sharply with pH and analysis of the variation of the rate constant with pH identifies a reaction pathway via both the mono- and di-anion forms of ascorbate, with the latter being the more reactive. As expected the entropy of activation is large and negative. Some aspects of structure–reactivity trends are discussed.

The influence of β-cyclodextrin (β-CD) on the base-catalyzed hydrolysis reaction of 1-phenyl-1-propyl, 2-phenyl-1-propyl and 3-phenyl-1-propyl nitrites and on the nitrosation of pyrrolidine, piperidine and N-methylcyclohexylamine by the aforementioned alkyl nitrites (RONO) is studied in aqueous buffers of the amines and in an alkaline medium with [OH−] = 0.20 M. The hydrolysis reaction is catalyzed by the presence of β-CD owing to the formation of reactive 1:1 inclusion complexes between the alkyl nitrite and the ionized β-CD; the addition of potential inhibitors, such as dodecyltrimethylammonium bromide monomers, accelerates the reaction even more. The effect is quite significant in the case of 1-phenyl-1-propyl nitrite and is viewed as a case of allostery. In the presence of neutral β-CD, the nitrosation by 1-phenyl-1-propyl nitrite, either of pyrrolidine or piperidine, is inhibited by β-CD addition; however, the nitrosation reaction of piperidine by 2-phenyl-1-propyl nitrite is catalyzed (passing through a maximum) by β-CD, whereas the nitrosation of pyrrolidine promoted by 3-phenyl-1-propyl nitrite exhibits practically no change upon β-CD addition. In alkaline media (containing ionized β-CD) the nitrosation of pyrrolidine by 1-phenyl-1-propyl nitrite is inhibited by the presence of β-CD; in contrast, the nitrosation of both piperidine and N-methylcyclohexylamine is catalyzed in all cases, but the degree of catalysis depends not only on the alkyl nitrite structure, but also on the type and concentration of the amine. Kinetic results are quantitatively interpreted on the basis of the proposed reaction mechanism in each case, and the kinetic rate constants of the different steps are determined. Comparison of the results obtained in aqueous alkaline media and in aqueous buffers of the amines themselves allows us to establish important characteristics of the transition state of the reaction.

A new method for measuring the concentration of atmospheric alcohols was developed and applied to ambient air samples. In the method, air samples were collected in 200 ml Pyrex glass bottles whose surface had been cleaned and treated with a chromic acid mixture. Alcohols in the sample were allowed to react in the dark with intentionally added nitrogen dioxide (200 ppm by volume (ppmv) concentration level) on the glass surface to yield corresponding alkyl nitrites. The concentration of the nitrite thus yielded is determined separately by gas chromatography (GC) with an electron capture detector (ECD). Alcohol concentration in the sample is calculated using a calibrated conversion factor of each alcohol to its nitrite. Detection limits for methanol, ethanol, and isopropanol are 0.9, 0.7, and 1.8 ppbv (parts per billion by volume), respectively, using 500 μl injection of the reaction mixture by this method. In order to examine the feasibility of this method for an ambient air sample, several measurements were done. Air samples were taken on a road with heavy traffic near the campus of Osaka Prefecture University. Concentration levels of methanol, ethanol, and isopropanol were 4–10, 3–25, and 1.5–20 ppbv, respectively. Diurnal variation of these alcohols’ concentration was also measured. Generally, alcohol concentrations were higher in the evening than those in the daytime, increasing up to the levels of 10–20, 10–25, and 10–20 ppbv for methanol, ethanol, and isopropanol, respectively.