Hydroxamoyl chlorides

The reaction of nitroalkenes or nitroalkanes with TiCl4 and Me3SiN3 gives a-azido functionalized hydroxamoyl chlorides, which act as precursors of nitrile oxides (Eq. 6.34).59... 

Glycosyl nitrile oxides 315, generated in situ by reaction of hydroxamoyl chlorides with DBU, participate in 1,3-dipolar cycloaddition with substituted alkenes leading to glycosyl isoxazolines the l,2,5-oxadiazole-2-oxides 316 are isolated as by-products in low yields (Scheme 79) <2004CHC353>. 

Macrocycles containing isoxazoline or isoxazole ring systems, potential receptors in host—guest chemistry, have been prepared by multiple (double, triple or quadruple) 1,3-dipolar cycloadditions of nitrile oxides, (prepared in situ from hydroxamoyl chlorides) to bifunctional calixarenes, ethylene glycols, or silanes containing unsaturated ester or alkene moieties (453). This one-pot synthetic method has been readily extended to the preparation of different types of macrocycles such as cyclophanes, bis-calix[4]arenes and sila-macrocycles. The ring size of macrocycles can be controlled by appropriate choices of the nitrile oxide precursors and the bifunctional dipolarophiles. Multiple cycloadditive macrocy-clization is a potentially useful method for the synthesis of macrocycles. 

Another path to such vicinal nitronitroso derivatives and then to 4-nitroisoxazoles is based on the treatment of a-nitro ketones with hydroxamoyl chlorides [528] (Scheme 87). 

In two examples, type 2 reagents produce 4-nitroisoxazoles. Nitro-keteneaminals undergo cycloaddition with nitrile oxides to produce the 4-nitroisoxazoles 61 (10-25%) [(Eq. 19)].30 Substrates possessing a methylene group activated on one side by a nitro group and on the other by either a nitrile or a carbonyl, react with hydroxamoyl chlorides in presence of base to produce the 4-nitroisoxazoles (62) and (63) [Eqs. (20,21)].57... 

In more detailed accounts, a range of aromatic and aliphatic nitrile A -oxides, prepared in situ by reaction of the corresponding hydroxamoyl chloride with triethylamine, underwent cycloaddition to 1,3,3-trimethylcylopropene to give 2-oxa-3-azabicyclo[3.1.0]hex-3-enes... 

A solution of EtjN (10 12nimol) in anhyd EtjO (10-15 mL) was added over 5 min to a stirred solution of the hydroxamoyl chloride (10-12 mmol) and the cyclopropene (19 24 mmol) in 12 (30-40 mL) at — 10 to — 15 C EtjNHCl precipitated. The mixture was kept at 20"C for 1 2 d and the precipitate was filtered off removal of the solvent gave the adduct which was recrystallized from pentane/Et20 (2 1). 

When the reaction of an aminophenol with A -ethoxycarbonylthioamide or a dithioate ester is applied to an aminothiophenol, a high yield of benzothiazole is obtained [2860, 2899]. The same substrate is converted into a benzothiazole efficiently at ambient temperature with hydroxamoyl chloride (the chloride of a hydroxamic acid) [3468]. Similar compounds in which the 2-phenyl group is varied are of interest as dye intermediates and are synthesized from quinonoid aminothiols [3477] the chemistry of quinonoid heterocyclcs has been reviewed [2947, 3650]. 

A hydroxamoyl chloride reacts with a C—C double bond of a 1,4-quinone in the presence of silver oxide as base and oxidant. The chemistry of heterocyclic quinones has been reviewed [2947, 3650]. Addition of a nitrile oxide (review of reactions [B-43,2115]) across the a,i -double bond of a butenolide leads to a new fused isoxazole ring. Cycloheptatriene undergoes a [6 + 2]n-cycloaddition at the 2,7-positions when it is stirred at room temperature for 4 days with nitrosoben-zene [2875]. 

Dioxoindoxazenes (68 R1 = aryl or heteroaryl, R3 = alkyl), formed by 1,3-dipolar cycloaddition of the appropriate nitrile oxide to a 1,4-benzoquinone, have bactericidal and fungicidal properties.87 Apparently, optimum yields of 68 are obtained by generating the nitrile oxide in situ from the hydroxamoyl chloride. 

The nomenclature of the imidoyl halides is not clearly established I have therefore attempted to select names which identify the compounds as imidoyl halides, and which furthermore, relate to their chemistry. For example. Chemical Abstracts lists the hydroxamoyl chlorides as oximes of the corresponding carboxylic acid chlorides. Although this name is formally correct, it does not reflect the chemistry of this class of compounds, which is closely related to hydroxamic acids, its hydrolysis products. 

The hydrolysis of hydroxamoyl chlorides, observed by Souchay et a/.( ), also occurs via an elimination sequence, with formation of the corresponding nitrile oxide intermediate. Likewise, solvolysis of N,N -disubstituted chloroformamidines may involve the carbodiimide as the reactive intermediate. 

Substituted hydroxamoyl chlorides were synthesized for the first time by Werner and his students in 1894. In the same year, the parent hydroxamoyl chloride was obtained by Nef. 

The nomenclature of this class of compounds is not at all clear. For example, the following names can be found in the literature hydroxamic acid chlorides, hydroxamic chlorides, hydroximic chlorides (Beilstein lists them as Hydroximsaure chloride ), and acyl and aroylchloride oximes. The latter names are used by Chemical Abstracts, Although the name benzoyl chloride oxime for benzhydroxamoyl chloride is formally correct, it does not reflect the close relationship between hydroxamoyl chlorides and hydroxamic acids, their hydrolysis products. In order to be consistent with the nomenclature used in the earlier chapters, I prefer the term hydroxamoyl to hydroxamic chloride. The interrelationship of the halides with the corresponding acids is shown below, and R is representative of the alkyl, aryl, acyl, aroyl, and carbalkoxy group. 

The standard displacement reactions of the chloro group and the elimination to nitrile oxides have been studied by Werner and his co-workers. Weygand and Bauer in 1927 studied the reaction of hydroxamoyl chlorides with alkali salts of ethyl cyanoacetate they obtained isoxazole derivatives. Likewise, Quilico and his students utilized hydroxamoyl chlorides to synthesize numerous isoxazole derivatives. 

One of the most important reactions of hydroxamoyl chlorides involves dehydrochlorination to nitrile oxides, and the renewed interest in the 1,3-cycloaddition reactions has focused attention again on the nitrile oxide precursors. 

In view of the ready availability of hydroxamoyl chlorides, and their numerous possibilities for transformations, they will most certainly become more important in the years to come. 

The chlorination of aldoximes I is the classical method of synthesis of hydroxamoyl chlorides II. Werner and his co-workers in 1894 ( 5-69 this method to synthesize a variety of aromatic hydroxamoyl chlorides. 

Phenylbenzhydroxamoyl Chloride ( ). To 10 g 4-phenylbenzaldoxime suspended in 50 ml of SN hydrochloric acid at 0°C an equivalent amount of chlorine is added. The resulting crude hydroxamoyl chloride (11 g, 94 %) is removed by filtration, and recrystallization from cyclohexane yields pure 4-phenylbenzhydroxamoyl chloride, m.p. 129-130°C. 

If the chlorination of aliphatic oximes is conducted in diethyl ether at — 60 C, aliphatic nitroso compounds III are obtained, which are in equilibrium with their dimeric form IV. The nitroso compounds on standing gradually isomerize to the hydroxamoyl chlorides II ( ). 

However, isonitrosoacetone reacts with chlorine in chloroform with formation of the oxime V rather than the hydroxamoyl chloride ( ). The formation of the hydroxamoyl chloride has previously been postulated ( ). 

The addition of hydrogen chloride to nitrile oxides VII produces hydroxamoyl chlorides in high yield However, this method is only of... 

Hydroxamoyl chlorides from nitrile oxides. General procedure ( ). To a solution of 0.01 mole of the corresponding nitrile oxide in 10 ml of methylene chloride and 5 ml of anhydrous diethyl ether, excess hydrogen chloride is added with ice-cooling. Evaporation of the solvents under vacuum, and recrystallization from benzene/ligroine affords the hydroxamoyl chlorides, usually in high yield. 

The parent hydroxamoyl chloride X was obtained by heating salts of fulminic acid XI with dilute hydrochloric acid ( ). 

The hydroxamoyl chloride X is stable at 0°C for some time, but upon warming rapid decomposition occurs, with formation of hydroxylamine hydrochloride ( ). This hydroxamoyl chloride is a lachrimator and vesicant, and it causes severe headaches therefore, it should be handled with caution ( ). 

The reaction of aromatic nitrile oxides with methanesulfonyl and benzylsulfonyl chloride in the presence of triethylamine yields the sulfonate esters of hydroxamoyl chlorides XII ( ). 

The infrared spectra of several hydroxamoyl chlorides were investigated by Navech and co-workers ( ), and it was demonstrated by ultraviolet spectroscopy that the hydrolysis of hydroxamoyl chlorides to nitrile oxides, as well as the reverse reaction, obeys second-order kinetics... 

The reaction of hydroxamoyl chlorides with water affords hydroxamic acids XVI (3.65,69)... 

Nucleophilic attack of hydroxamoyl chlorides by alkoxide ion similarly affords the corresponding ethers (XVII)... 

If hydroxamoyl chlorides are treated with the silver salt of benzoic acid the N-benzoate XVIII is obtained via rearrangement of the initially formed O-benzoate XIX... 

The reaction of aliphatic hydroxamoyl chlorides with thiophenols in the presence of triethylamine was used by Benn to synthesize the thio-hydroxamic ethers XX ( ). 

Aminocarboxylic acid esters undergo reaction with hydroxamoyl chloride in a similar fashion to yield the substitution products XXIV however, saponification of the ester group occurs, unless carboxyethyl-hydroxamoyl chloride is being used ( ),... 

In the reaction of 2-aminopyridine with carboxyethylhydroxamoyl chloride the bicyclic compound XXVll is obtained ( ), and amidines generally form 1,2,4-oxadiazoles upon treatment with hydroxamoyl chlorides ( ). 

When hydroxylamine is allowed to react with hydroxamoyl chlorides, attack on nitrogen occurs with formation of the hydroxylamino-oximes XXVIII (3 ). 

The reaction of hydroxamoyl chlorides with hydrazine has also been investigated and hydrazide-oximes XXIX (. 69 obtained. However, the hydrazine derivative XXX yields N-substituted 2-amino-5-methyl-mercapto-l,3,4-thiadiazoles XXXI upon reaction with hydroxamoyl chlorides ( ). 

Azide ion attacks hydroxamoyl chloride readily, and the linear reaction product cyclizes instantaneously to yield the isolated tetrazole derivative XXXII ( "). 

The displacement of the chloro group in hydroxamoyl chlorides by sodium ethyl cyanoacetate was first demonstrated by Weygand and Bauer in 1927. ( ). The intermediate linear compound XXXIV cyclizes readily to the corresponding isoxazole derivative (XXXV)... 

The elimination of hydrogen chloride from hydroxamoyl chlorides occurs in refluxing toluene, as evidenced by the fact that the 1,3-cycloadducts of benzonitrile oxide with olefins and acetylenes are obtained For... 

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