Chloramines sources

The metal catalyst is not absolutely required for the aziridination reaction, and other positive nitrogen sources may also be used. After some years of optimization of the reactions of alkenes with positive nitrogen sources in the presence of bromine equivalents, Sharpless et al. reported the utility of chloramine-T in alkene aziridinations [24]. Electron-rich or electron-neutral alkenes react with the anhydrous chloramines and phenyltrimethylammonium tribromide in acetonitrile at ambient temperature, with allylic alcohols being particularly good substrates for the reaction (Schemes 4.18 and 4.19). 

Chloramine-T also functions as a nitrene source in the presence of heteropoly acids (HPAs) such as phosphomolybdic and phosphotungstic acids. The aziridination of alkenes by treatment with the combination of HPA and chloramine-T is... 

Bromamine-T can also be utilized as a nitrene source, as reported by Zhang et al. [27]. Fe(in) porphyrins such as Fe(TPPC)Cl (Figure 4.2) thus catalyze the aziridination of alkenes when bromamine-T is used, whereas chloramine-T was inactive and iodinanes were inefficient reagents. 

Two methods that are particularly convenient for large-scale synthesis of aziridines are discussed below. Both utilize readily available chloramine salts, such as chloramine-T, as sources of nitrogen. The first method involves direct olefin azir-idination catalyzed by phenyltrimethylammonium tribromide (PhNMe3+Br3 PTAB) [42]. In the second method, 1,2-hydroxysulfonamides, conveniently obtained by osmium-catalyzed aminohydroxylation of olefins, are converted into aziridines by one-pot cyclodehydration. 

Despite the effectiveness of chloramine-T in this new method, removal of the toluenesulfonyl group from the newly introduced nitrogen substituent requires harsh conditions. The finding that the N-chloramine salt of tert-butylsulfonamide is also an efficient nitrogen source and the terminal oxidant for aziridination of... 

A more practical, atom-economic and environmentally benign aziridination protocol is the use of chloramine-T or bromamine-T as nitrene source, which leads to NaCl or NaBr as the sole reaction by-product. In 2001, Gross reported an iron corrole catalyzed aziridination of styrenes with chloramine-T [83]. With iron corrole as catalyst, the aziridination can be performed rmder air atmosphere conditions, affording aziridines in moderate product yields (48-60%). In 2004, Zhang described an aziridination with bromamine-T as nitrene source and [Fe(TTP)Cl] as catalyst [84]. This catalytic system is effective for a variety of alkenes, including aromatic, aliphatic, cyclic, and acyclic alkenes, as well as cx,p-unsaturated esters (Scheme 28). Moderate to low stereoselectivities for 1,2-disubstituted alkenes were observed indicating the involvement of radical intermediate. 

While nitrogen sources such as chloramine-T and PhI=NTs have been used for aziridination reactions, TsNC12 has not been explored until now. The reaction of TsNCL, with Pd(OAc)2 and K2C03 provides the expected N-tosyl aziridines in good yields <06TL7225>. This reaction presumably proceeds through an initial amidohalogenation reaction catalyzed by palladium. The chloroamide is then converted to the aziridine via an intramolecular substitution reaction. 

When the addition is completed, the heat source is removed and the dark-colored contents are allowed to cool until another 0.25 mole of ethereal chloramine has been prepared and is ready for use a wait of 1.5-2 hours between chloramine additions is convenient but not essential to the success of the experiment. The cooled reaction mixture is then reheated to 150°, and the process is repeated. This sequence is repeated until a total of four 0.25-mole portions of chloramine are added. 

Iodine was found to be an efficient catalyst for the aziridination of alkenes (Scheme 6) utilizing chloramine-T (A-chloro-A-sodio-p-toluenesulfonamide) as the nitrogen source. For example, when 2 equiv. of styrene (45a) were added to chloramine-T in the presence of a catalytic amount of iodine (10mol%) in a 1 1 solvent mixture of acetonitrile and neutral buffer, the corresponding aziridine (46) was obtained in 91% yield. The reaction proved to work with other acyclic and cyclic alkenes, such as oct-l-ene and cyclohexene. The aziridination of para-substituted styrene derivatives (45b-e) demonstrated that, as expected for an electrophilic addition, electron-rich alkenes reacted faster than electron-poor alkenes. However, with 1 equiv. of I2, mainly iodohydrin (47) was formed. A catalytic cycle has been proposed to account for the fact that only a catalytic amount of iodine is required (Scheme 1) ... 

Recently, Duirk et al. [34] showed evidence that iodinated X-ray contrast media (ICM), such as iopamidol, constitute an iodine source to form iodo-THM DBFs, e.g., dichloroiodomethane, and iodo-acid DBFs, e.g., iodoacetic acid, in chlorinated and chloraminated drinking waters. However, the complete reaction pathway is not fully understood yet, and it is under further investigation. Chloraminated and chlorinated source waters with iopamidol were genotoxic and cytotoxic in mammalian cells. This is in agreement with the previously reported high genotoxicity and cytotoxicity of the iodo-acids and iodo-THMs [20, 21]. 

If nitration under acidic conditions could only be used for the nitration of the weakest of amine bases its use for the synthesis of secondary nitramines would be severely limited. An important discovery by Wright and co-workers " found that the nitrations of the more basic amines are strongly catalyzed by chloride ion. This is explained by the fact that chloride ion, in the form of anhydrous zinc chloride, the hydrochloride salt of the amine, or dissolved gaseous hydrogen chloride, is a source of electropositive chlorine under the oxidizing conditions of nitration and this can react with the free amine to form an intermediate chloramine. The corresponding chloramines are readily nitrated with the loss of electropositive chlorine and the formation of the secondary nitramine in a catalytic cycle (Equations 5.2, 5.3 and 5.4). The mechanism of this reaction is proposed to involve chlorine acetate as the source of electropositive chlorine but other species may play a role. The success of the reaction appears to be due to the chloramines being weaker bases than the parent amines. 

Acetic anhydride-nitric acid mixtures are extensively used for chloride-catalyzed nitrations. Other nitrating agents have been used and involve similar sources of electropositive chlorine for intermediate chloramine formation. 4,10-Dinitro-4,10-diaza-2,6,8,12-tetraoxaisowurtzitane (TEX) (40), an insensitive high performance explosive (VOD 8665 m/s, d = 1.99 g/cm ), is synthesized by treating the dihydrochloride salt of the corresponding amine (39) with strong mixed acid. ... 

Alkenes can be aziridinated using a variety of nitrogen sources. Among the recently reported systems are Chloramine T (iV-chloro-A -sodio-p-toluenesulfonamide) with pyridinium hydrobromide perbromide catalyst (c.g., 119 120) <99OL705>, the A -chloramine salt of t-... 

Generally, sulfonamides, carbamates, or amides are employed as nitrogen source giving access to different reaction courses. The first example of the sulfonamide variant was reported in 1996, and it relied on the use of Chloramine-T (32) [73]. To achieve reasonable catalytic... 

Studies on the structural effects of the nitrogen source revealed that the enantiopurities could be increased from 81 to 95% ee by changing from Chloramine-T (32) to Chloramine-M (33) [74]. Furthermore, reactions with the latter were ligand-accelerated, whereas transformations with the former were not. 

The first reports on iron-catalyzed aziridinations date back to 1984, when Mansuy et al. reported that iron and manganese porphyrin catalysts were able to transfer a nitrene moiety on to alkenes [90]. They used iminoiodinanes PhIN=R (R = tosyl) as the nitrene source. However, yields remained low (up to 55% for styrene aziridination). It was suggested that the active intermediate formed during the reaction was an Fev=NTs complex and that this complex would transfer the NTs moiety to the alkene [91-93]. However, the catalytic performance was hampered by the rapid iron-catalyzed decomposition of PhI=NTs into iodobenzene and sulfonamide. Other reports on aziridination reactions with iron porphyrins or corroles and nitrene sources such as bromamine-T or chloramine-T have been published [94], An asymmetric variant was presented by Marchon and coworkers [95]. Biomimetic systems such as those mentioned above will be dealt with elsewhere. 

The use of /V-chloramines, in principle, allows the facile generation of aminyl radicals upon UV photolysis in neutral media. A radical chain can be envisioned for the formation of 2-chIoromethylpyrrolidines (Scheme 7). In practice, however, there is a slow step in this sequence, step A and/or B, such that other reaction pathways, disproportionation or H-abstraction from the solvent, compete. Surzur has studied the reaction in Scheme 7 in the alcoholic solvents MeOH and /-PrOH, which serve as hydrogen atom sources, and achieved acceptable ratios of cyclic products 25 and 26 to acyclic amine 27 (70TL3107). Other /V-chloroalkenylamines gave similar results (71TL903 80TL287). /8-chloro-substituted amine products such as 25 were the sole products when the reactions were carried out in acetic acid-water mixtures these reactions involve aminium cation radicals and are discussed further in Section III,B. 

This test is performed to determine the amount of cyanide in the sample that would react with chlorine. Not all cyanides in a sample are amenable to chlorination. While HCN, alkali metal cyanides, and CN- of some complex cyanides react with chlorine, cyanide in certain complexes that are tightly bound to the metal ions are not decomposed by chlorine. Calcium hypochlorite, sodium hypochlorite, and chloramine are some of the common chlorinating agents that may be used as a source of chlorine. The chlorination reaction is performed at a pH between 11 and 12. Under such an alkaline condition, cyanide reacts with chlorine to form cyanogen chloride, a gas at room temperature, which escapes out. Cyanide amenable to chlorination is therefore calculated as the total cyanide content initially in the sample minus the total cyanide left in the sample after chlorine treatment. 

As stated in the introduction, chloramine-T (where T denotes three crystalline water molecules) is a commonly used nitrene precursor, which is commercially available and costs less than do most other nitrene sources. The benefit of a silver salt in nitrene transfer reactions with chloramine-T is surprisingly simple. Because silver chloride is insoluble in most solvents, substoichiometric amounts of silver salts (like silver nitrate) can be used to remove the chloride from chloramine to facilitate the release of a free nitrene radical, which can aziridinate olefins. Since the amount of silver is near stoichiometric, it should not be called silver-based catalysis, although turnover numbers (TONs) higher than 1 have been observed in some cases. 

Scheme 6.2. Olefin aziridination using chloramine-T as a nitrene source.

More recently, chloramine-T (CT) was found to be an efficient nitrogen source for the aziridination of olefins by our group [7a], Among the transition metals, copper(I) chloride was the most suitable catalyst for the aziridination of olefins with CT. For example, frans-P-methylstyrene was successfully aziridinated with CT at 25 °C in acetonitrile in the presence of a catalytic amount of CuCl (Scheme 6). Other olefins have also been aziridinated by the reaction, whose products are shown in Scheme 7. 

An alternative procedure to afford the chiral nitridomanganese complex 15 was developed by our group. This procedure consists of a reaction of the chiral Mnra complex 14 [21] with gaseous NH3 and chloramine-T as the oxidant in MeOH [22] (Scheme 15). Other derivatives 16-21 which have (1 / ,2/ )-diaminocyclohex-ane as a backbone were synthesized by the usual method using aqueous NH3 and NaOCl. Complex 22 was also synthesized from diphenylethylenediamine as a chiral source (Scheme 16). 

Some of the nitrogen sources mentioned above (e.g., Chloramine-T and N-bromoacetamide) are commercially available. In other cases, the chloramine salts have to be prepared in situ by treating the amide with ferf-butyl hypochlorite [32] and sodium hydroxide [15]. It has been found that the unstable tert-... 

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