Chloroamines, formation

In 2007 Kocovsky and Malkov reported an alternative organocatalytic approach, taking advantage of trichlorosilane in combination with a chiral formamide ligand (now referred to as Sigamide) for chloroamine formation (Scheme 7.6) and subse quent conversion to highly enantioenriched aziridines (not shown) [21]. 

When formation of either the five- or six-membered ring was possible for N-chloroamine 37, only the five-membered ring was conducive under the Hofmann-Ldffler-Freytag reaction conditions, forming exclusively 6-ethyl-6-aza-bicyclo[3.2.1]-octane (38). No 2-ethyl-2-aza-bicyclo[2.2.2]-octane (39) was observed. On the other hand, 2-methyl-2-aza-bicyclo[2,2.2]octan-6-one (41) was installed by UV irradiation of a solution of A -chloroamine 40 in TFA. Ironically, when the ketone functionality on 40 was protected as its ethylene ketal group, the resultant steric interactions completely prohibited the classic Hofmann-Loffler-Freytag reaction. 

Oxidation of enzyme sulphydryl groups by free radicals (Armstrong and Buchanan, 1978) and by the longer lived chloroamines (Weiss et al., 1983), contributes to enzymic dysfunction and to the decrease in serum sulphydryl levels, primarily mercaptoalbumin, found in coalworkers with rheumatoid inflammatory disease (Thomas and Evans, 1975). Formation of the S-nitroso adduct of plasma mercaptalbumin is thought to provide a metastable reservoir for intravascular nitric oxide release (Stamler etal., 1992). 

Gassman pioneered the use of Al-chloroamines for the formation of both alkyl and arylnitrenium Several examples are given in Figs. 13.10 and... 

The synthesis of pyrrolidines by the free radical transformation of (V-chloroamines, the Hofmann-Loeffler-Freytag reaction, is of preparative significance. The key step is the formation of a radical cation which abstracts hydrogen intramolecularly to form a carbon-based radical (Scheme 21(a)). This species then abstracts chlorine from another TV-chloroamine (60JA1657, 50JA2118). The observed positional selectivity for hydrogen abstraction is a consequence of the preferred adoption of a six-membered transition state. A typical conversion achieved is indicated in Scheme 21(b). 

A study of the decomposition of /f-hydroxy-/V-chloroamines in aqueous medium has established that pre-equilibrium formation of the conjugate alcoholate is a prerequisite feature of the competing fragmentation and intramolecular elimination paths (Scheme 13).98 A very high effective molarity (EM = 2 x 105 M) has been estimated for the intramolecular process, which cannot occur in the case of (/V-chloro)butylethanolaminc. For reaction of (A-c h I o ro )ct hy I cth an o I am i nc kmln/k g = 6.1 and the solvent isotope effect ( oh- /koo- )obs = 0.68 is consistent with pre-equilibrium deprotonation followed by a unimolecular reaction in which there is no participation by solvent. 

The electrolysis of 2-amino- 1-cycloalkanol 15 in an MeCN/H20—NaCl—(Pt) system at pH 4 (buffered) yields keto nitrile 16 in 62% yield (Scheme 3-5)52). The formation of 16 can be explained by fragmentation of the intermediate 6e/a-hydroxy-,V-chloroamine and the subsequent further oxidation with [Cl]+. 

Reaction of hypochlorous acid with ammonia leads to rapid formation of chloroamine, step (1) . Reaction of the product with ammonia forms hydrazine (2) and this last may then form nitrogen (3), viz. 

Intermediate formation of hydroxylamine was confirmed by an isotope dilution method. Only low concentrations were present at any time, due to the speed of its reaction with chloroamine. A side product in presence of oxygen is peroxynitrite which probably forms from hydroxylamine. The rates of hydrolysis below 1 M OH obey the expression... 

The reaction of l,2-dithiole-3-thiones with chloramine-T results in formation of analogous nitrogen compounds (e.g., 160), which may lose the exocyclic sulfur atom to form 161.220 Other N-chloroamines have been used.22 1,222 The chemistry of these imines has been studied.223 230... 

Almost all N-aminopyrazoles were obtained by the amination of pyrazole or its derivatives with HOSA or MSH (Table 11). Only on formation of l-amino-3,5-dimethylpyrazole having the - N label was labeled chloroamine used. As a rule, yields of N-aminopyrazoles are rather high, but with an increase in the number and size of substituents on the ring, yields decrease. 3(5)-methyl- and 3(5)-aminopyrazolcs are aminated with the formation of a nearly inseparable mixture of I-NH2-3-R- and I-NH2-5-R-pyrazoles in a 1 1 ratio. However, if the substituent at position 3 is more bulky, the main or even the dominant component in the mixture is l-NH2-3-R-pyrazole (compare for, instance, data for 3-ethyl- and 3-phenylpyrazoles in Table II). No doubt, this is the result of steric interference by the substituent. 

Another synthesis of a quaternary salt (8) was developed by Meyer and Sapianchiay for the purpose of studying the steric course of formation of the pyrrolizidine system.9 Photolysis of the N-chloroamine (9) in a Hofmann-Loeffler-Freytag reaction [Eq. (4)], gave an intermediate that yielded the pyrrolizidine salt (8) in an intramolecular N-alkylation. The product was the cis-isomer, reflecting the greater degree of strain in the trans-fusion of two five-membered rings. 

As we were not only interested in the development of a racemization method but also wanted to evaluate an asymmetric synthesis articulated around the imine intermediate 7 vide infra), we initially investigated its controlled preparation by oxidation of the unwanted (7 )-TH[3C 4 obtained from the mother liquors. Among the various methods initially tested, good results (approximately 75 to 80% in situ yield of imine 7) were obtained with NaOCl in methanol/THF at 0 to 5°C for 3 h. The major by-product is the overoxidized (3-carboline derivative (5 to 10%), although in some experiments, low levels of the unstable N-chloroamine intermediate were also detected. Later on, approximately 68% in situ yield was obtained with tetra-n-propylammonium perruthenate (0.05 equiv) as catalyst with iV-methylmorpholine oxide (1.5 equiv) as cooxidant in acetonitrile at room temperature. However, in this latter method, up to 16% of totally oxidized (3-carboline was also formed. The imine 7 was then directly reduced with sodium borohydride to produce the racemic material in approximately 50% isolated overall yield. Although the aromatic (3-carboline by-product was easily removed upon salt formation, the above approach suffered from several major drawbacks difficulty to control the overoxidation of the desired dihydro-(3-carboline to the (3-carboline on... 

The cationic intermediates also can be captured by solvent. Halogenation with solvent capture is a synthetically important reaction, especially for the preparation of chlorohydrins and bromohydrins. Chlorohydrins can be prepared using various sources of electrophilic chlorine. Chloroamine T is a convenient reagent for chloro-hydrin formation. Bromohydrins are prepared using NBS and an aqueous solvent mixture with acetone or THF. DMSO has also been recommended as a solvent. These reactions are regioselective, with the nucleophile water introduced at the more-substituted position. 

Following upon closely related earlier work, it has been found that photolysis of the iV-chloroamine (3) leads to loss of the piperidine ring as 5-methyl-A -piperideine and formation of the C-20 diastereoisomeric derivatives (4). 

Organoboranes can be used for the synthesis of various organic compounds containing an amino group . The most common procedures involve the reaction of organoboranes with azides, with hydroxylamine derivatives, or with chloroamines. All amination reactions proceed via intermediate formation of a borate complex followed by anionotropic rearrangement to form the new C—N bond (Equation (21)). 

Photolysis (Hg lamp) of aqueous solutions of [M(NH3)5N3] (M = Rh or Ir) in dilute HCl has been shown to yield the chloroamine complexes [M-(NH3)5(NH2C1)] as the primary products. Since one molecule of dinitrogen was also produced, even in the presence of added 1 or acrylamide scavengers, the involvement of azide radicals was eliminated. Instead the mechanism in Scheme 9 (M = Rh) was proposed, and the formation of such a co-ordinated... 

Ferrous ions are similarly employed in the production of radicals from N-chloroamines and hydroperoxides. The transfer of one electron to or from a species containing only paired electrons results in the formation of free radicals. Electron transfer can occur both from charged and neutral molecules (Scheme 4.12). 

Scheme 10.16. The formation of 1,2-dimethylazacyclopentane (1,2-dimethylpyrroUdme) by radical cleavage and loss of HCl from the corresponding iV-chloroamine.

Compounds whose structure possesses a weakly acidic NH group, such as primary amines, amides, imides, and lactam can be detected by performing a redox reaction through the formation of intermediary N-chloro derivatives. Potassium permanganate reacting with hydrochloric acid generates chlorine (probably at oxidation state +1), which transforms the invoked derivatives in N-chloroamines. The latter derivatives oxidize iodide ions into iodine detected with a starch solution ... 

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