Hydroxylamine-O-sulfonic Acid

H2NOSO2OH

[2950-43-8]  · H3NO4S  · Hydroxylamine-O-sulfonic Acid  · (MW 113.11)

(amination; hydroxymethylation; reduction; conversion of alkenes to primary amines1-3)

Alternate Name: HOSA.

Physical Data: mp 210 °C (dec).

Solubility: sol cold water, methanol; slightly sol ethanol; insol ether, CHCl3.

Form Supplied in: white solid; widely available.

Analysis of Reagent Purity: quantitative analysis of HOSA can be made by iodometric titration.4,5

Preparative Methods: by reacting hydroxylamine sulfate with 30% fuming H2SO44 or 60% oleum6 at rt, or by heating a mixture of hydroxylamine sulfate and chlorosulfonic acid at 100 °C for several hours.5

Handling, Storage, and Precautions: hygroscopic; should be stored in tightly sealed bottles in a refrigerator. Aqueous solutions are unstable, decomposing rapidly above 25 °C. It is thus important to use freshly prepared solutions in reactions. Use in a fume hood.

Introduction.

The use of HOSA in organic synthesis results from its ability to act both as a nucleophile and as an electrophile (eq 1), as well as being able to provide an in situ route to other chemical entities, such as diimide.

Amination at Nitrogen.

Monosubstituted and 1,1-disubstituted hydrazines can be prepared in fair to good yields by reacting HOSA with primary or secondary amines, respectively, in basic aqueous solution (eq 2).7,8 Tertiary amines give 1,1,1-hydrazinium salts when they are treated with HOSA under basic conditions in aqueous or alcoholic solution (eq 3).7-9

Many nitrogen heterocycles, including pyridine,7,8 quinoline,7,8 pyrimidine,9 azetidine,10 pyridazine,11 tetrazole,12 indole (eq 4),13,14 benzimidazole,14,15 triazine,16 benzoxazole,17 and purine14,18 ring systems, can also be aminated on nitrogen using HOSA.

Amination at Carbon.

One of the two published reports on carbanion aminations with HOSA19 concerns its reaction with some b-diketo compounds to furnish symmetrically substituted pyrroles (eq 5).

The other attempted amination with HOSA20 yielded a trace amount of an amino acid from an a-lithiated carboxylic acid. Triphenylborane, prepared from phenylmagnesium bromide and boron trifluoride, reacts with HOSA to give aniline in 35% yield.21

Two different methods have been reported for the direct amination of an aromatic ring in low yields using HOSA. The first employs Aluminum Chloride as a catalyst (eq 6);22,23 the second is an homolytic amination procedure in which a protonated amino radical is generated using iron(II) ion together with HOSA (eq 7).24

Certain heterocycles react with HOSA to give C-substituted amino derivatives (eq 8).25

Amination at Sulfur.

Organosulfur compounds, including thiols,26 thioacids (eq 9),27 thioamides,27,28 dithioacids,27 and thioethers (eq 10),29 undergo amination with HOSA in good yields.

Hydroxymethylation.

Quinolines can be hydroxymethylated in the 2-and/or 4-position using HOSA in methanol (eq 11).30

Reduction.

HOSA, alone31 or together with hydroxylamine sulfate,32 provides under basic conditions a source of Diimide, HN=NH, which will reduce multiple bonds (eqs 12 and 13). Yields obtained by using HOSA alone seem to be lower compared with those obtained with HOSA-hydroxylamine sulfate.

Conversion of Alkenes into Primary Amines.

Methods for the conversion of alkenes into primary amines via the corresponding organoboranes using HOSA have been developed.33 -36 Organoboranes are prepared in situ by the addition of Diborane to the alkene in THF (eq 14)33 or by the addition of Boron Trifluoride Etherate to the alkene and Sodium Borohydride in diglyme, in which HOSA is soluble (eq 15).35

The limitation to quantitative utilization of the alkyl groups has been overcome by preparing a mixed organoborane, R1R22B, in which R1 shows a significantly greater migratory aptitude than R2. For this purpose, organodimethylboranes, prepared by hydroboration of alkenes with dimethylborane, were treated with HOSA to afford the corresponding primary amines stereospecifically in almost quantitative yields (eq 16).37

a-Chiral primary amines of high optical purity can be obtained from the chiral boronic esters through the intermediate formation of alkyl methyl borinic esters and their stereospecific reaction with HOSA in very good yields (eq 17).38,39 Synthesis of chiral a-methylorganyl primary amines, which are difficult to prepare via direct asymmetric hydroboration, can be accomplished by treating borinate esters with HOSA (eq 18).40

Conversion of Carboxylic Acids to Primary Amines.

Heating a carboxylic acid or its anhydride with HOSA in mineral oil at 160-180 °C41 or in polyphosphoric acid at 115-125 °C42 gives a primary amine in a low yield (eq 19).

Conversion of Primary Amines to Hydrocarbons (Reductive Deamination).

In an indirect route, a primary amine is converted into its sulfonamide which is isolated, dissolved in aqueous base, and then treated with HOSA to give the hydrocarbon in a high yield (eq 20).43 In a direct route, a primary amine is allowed to react with 2-3 equiv of base to give the hydrocarbon in a moderate yield (eq 21).44

Conversion of Carbonyl Compounds to Oxime Sulfonates.

Aldehydes and ketones react with HOSA in aqueous solution to give oxime-O-sulfonic acids and salts in good yields (eq 22).45,46

Conversion of Aldehydes to Nitriles.

With aldehydes, prolonged treatment with HOSA, at rt or above, generates nitriles (eq 23).46,47

Conversion of Ketones to Oximes.

Reaction of aliphatic ketones with HOSA at 100 °C gives oximes in high yields (eq 24).48 The method has the advantage over the standard oxime preparation procedure employing hydroxylamine hydrochloride in that no adjustment in pH of the reaction medium is required to facilitate reaction and a solvent is not necessary, the ketone and HOSA simply being mixed together.

Conversion of Ketones to Amides.

Under the conditions described above, alkyl aryl ketones yield N-aryl aliphatic amides, again in high yields (eq 25).48 Alicyclic ketones have been converted to lactams using HOSA (eq 26).49

Conversion of Oximes to Diazo Compounds.

Oximes react with HOSA in aqueous base to give diazo compounds (eq 27).50


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Ender Erdik

Ankara University, Turkey



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