HYDROLYSIS AND CHLORINATION OF THREE β-CHLOROETHYLAMINES<sup>1</sup>

Price, Charles C.; Pohland, Albert E; Velzen, Bernard H.

doi:10.1021/jo01166a017

Cited by 15 publications

(12 citation statements)

References 4 publications

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“…Various hydrolysis conditions, including unbuffered [41][42][43][44][45][46][47] and buffered 43,45,48,49 water solutions, and mixed solvents such as water-acetone solutions [50][51][52] have been employed to explore the kinetics and mechanisms of the chemistry of nitrogen mustards. A snapshot of general results is provided in the combined representative schematic (Fig.…”

Section: Stability and Aquationmentioning

confidence: 99%

Sulfur, oxygen, and nitrogen mustards: stability and reactivity

et al. 2012

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Mustard gas, bis(β-chloroethyl) sulfide (HD), is highly toxic and harmful to humans and the environment. It comprises one class of chemical warfare agents (CWAs) that was used in both World Wars I and II. The three basic analogues or surrogates are: the monochloro derivative, known as the half mustard, 2-chloroethyl ethyl sulfide (CEES); an oxygen analogue, bis(β-chloroethyl) ether (BCEE); and several nitrogen analogues based on the 2,2'-dichlorodiethylamine framework (e.g., HN1, HN2, and HN3). The origin of their toxicity is considered to be from the formation of three-membered heterocyclic ions, a reaction that is especially accelerated in aqueous solution. The reaction of these cyclic ion intermediates with a number of important biological species such as DNA, RNA and proteins causes cell toxicity and is responsible for the deleterious effects of the mustards. While a number of studies have been performed over the last century to determine the chemistry of these compounds, early studies suffered from a lack of more sophisticated NMR and X-ray techniques. It is now well-established that the sulfur and nitrogen mustards are highly reactive in water, while the oxygen analog is much more stable. In this study, we review and summarize results from previous studies, and add results of our own studies of the reactivity of these mustards toward various nonaqueous solvents and nucleophiles. In this manner a more comprehensive evaluation of the stability and reactivity of these related mustard compounds is achieved.

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Section: Stability and Aquationmentioning

confidence: 99%

Sulfur, oxygen, and nitrogen mustards: stability and reactivity

et al. 2012

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“…(3) The proven lability of the C-N bond in 2-chlorethylamine derivatives under mild oxidizing conditions in vitro. Chloracetaldehyde was identified among the products of treating tris-(2-chlorethyl)amine with aqueous hypochlorite at an acid pH [18]. Our own studies indicate that a lymphocyte-deactivating aldehyde, not identical with acrolein, is formed by treating cyclophosphamide with hydrogen peroxide in the presence of ferric ions and hydroquinone at an acid pH.…”

Section: Discussionmentioning

confidence: 82%

Some (pharmacological) properties of chloracetaldehyde, an oxidation product and potential metabolite of cyclophosphamide

1974

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Circumstantial evidence is presented that chloracetaldehyde is generated from cyclophosphamide by chemical oxidation in vitro with peroxide and might possibly be formed in vivo as a product of cyclophosphamide bioaetivalion. Chloracetaldehyde has several attributes of an agent capable of suppressing cellular immunity. Thus it prevents a graft-versus-host reaction (both in vivo and in vitro), is cytostatic and under certain conditions can abrogate an ongoing immunopathy (EAE).These properties are also exhibited by HN-2 and certain alkylating metabolites of cyclophosphamide.

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“…The hydrolysis studies suggest that the solubility may be as high as 0.8% (8 g/L). 212 A recent review 17 reports two different values; both appear to be erroneous. Table 1 in the reference appears to be a typographical error, reporting the 12 g/L solubility of the methyl analogue (HN2) 210 as applying to HN1.…”

Section: The Density Of Nn-bis(2-chloroethyl)-n-ethylaminementioning

confidence: 99%