Protection of sulfonic acids

Few methods exist for the protection of sulfonic acids. Imidazolides and phenolic esters are too base labile to be useful in most cases. Simple sulfonate esters often cannot be used because these are obviously quite susceptible to nucleophilic reagents. 

The neopentyl sulfonate, prepared from the sulfonyl chloride (Pyr, 95% yield), is cleaved nucleophilically under rather severe conditions (Me4NCl, DMF, 160°C, 16 h, 100% yield). These may also be cleaved by acidolysis (CH3CN, H2O, 0.1% TFA, 4-5 days), with LiBr, butanone, reflux, 48 h, or liquid HF, ra-cresol, 100% yield.  

This sulfonate, prepared from B0CNHCH2CH2C(CH3)CH20H and the sulfonyl chloride (Pyr, 100% yield), is cleaved by initial BOC cleavage to release the free amine after pH adjustment to 7-8. Intramolecular displacement occurs to release the sulfonate and a pyrrolidine.  

The isobutyl sulfonate was examined as a replacement for the isopropyl sulfonate that had undesirable stability properties. Cleavage occurs with 2 eq. of B114NI and proceeds much more readily than cleavage of the isopropyl sulfonate.  

This sulfonate is cleaved with BU4NI or ammonia. The group has been reported to suffer from stability problems upon storage and use.  

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Andrianov, A. K., Marin, A., Chen, J., Sargent, J. and Corbett, N. 2004. Novel route to sulfonated polyphosphazenes Single-step synthesis using "noncova-lent protection" of sulfonic acid functionality. Macromolecules 37 4075 4080. 

Meese, C.O. 1984. 2,2,2-Trifluorodiazoethane a highly selective reagent for the protection of sulfonic acids. Synthesis 1041-1042. 

Materials that are corrosion resistant to the expected cathodic polarization qualify as impressed current cathodes. Austenitic CrNi steels are used with strong acids. The oleum (i.e., fuming sulfuric acid) and concentrated sulfuric acid tanks used in sulfonating alkanes and in the neutralization of sulfonic acids are anodi-cally protected using platinized brass as cathodes [15]. Lead cathodes are used to protect titanium heat exchangers in rayon spinning baths [16]. 

Manufacturers of a multicomponent mixture of fatty acids, salts of sulfonic acid and stabilizing polar compounds (such as sodium octonate) claim that it provides concrete extra protection by creating ultra-stable air bubbles that are small and closely spaced [5]. In addition to many advantages, it can be used in fly ash concrete containing large amounts of... 

Attempts to convert the Akacyl derivatives of the moderately stable a-amino sulfonic acids by turning them into sulfonyl chlorides and then directly to sulfonamides have failed it appears that the critical requirement for C-S bond rupture is related to a sufficient activation of the sulfonate. 1061 Any synthetic approach to the desired sulfonamide derivatives which utilizes N-protection of aminomethane sulfonic acid as the initial step seems to offer little likelihood of success. In the context of the overactivation of the sulfonyl group of N-protected aminoalkyl sulfonic acid, (l-elimination of the S02C1 is favored over the corresponding sulfonamide, with amines acting merely as bases, not as nucleophiles (Scheme 24). 107 ... 

This Chapter contains reactions which prepare the oxides of nitrogen, sulfur, and selenium. Included are N-oxides, nitroso, nitro compounds, nitrile oxides, sulfoxides, selenoxides, and sulfones. Oximes are found in Sections 60A (Protection of Aldehydes) and 180A (Protection of Ketones). Preparation of sulfonic acid derivatives are found in Chapter Two and the preparation of sulfonates in Chapter Ten. 

Amongst the previously proposed AT-sulfonyl derivatives, the Mtr group has most frequently been used for the side-chain protection of lysine,although it has occasionally been used for N -protection of amino acids.It is cleaved by strong acids such as 0.3 M methane-sulfonic acid in TFA/thioanisole (9 1) at room temperature within 1 hour.t l... 

Protection of Carboxylic Acids. 2 -Hydroxyethyl phenyl sulfone (1) Is a useful reagent for the protection of carboxylic acids. Thus, treatment of the protected muramic add derivative (2) with (1) and DCC afforded the 2 (phenylsulfonyl)ethyl ester (3) in excellent yield (eq 1). ... 

Protection of amino groups as azo compounds Sym. diaryls from aryl halides Replacement of sulfonic acid groups by hydrogen and partial replacement by hydroxyl... 

The cyclic dimerization of HIBA proceeded smoothly in the presence of the dehydration catalyst methane sulfonic acid to isolate the cyclic dimer TMG in a 67% 5deld. Another simple and convenient route for the s5mthesis of TMG from lactic acid has been reported [102]. This method involves three steps (1) one-step protection of lactic acid hy cyclic acetalization employing acetone (2) cc-methylation of the obtained 2,2,5-trimethyl-l,3-dioxolan-4-one and [3] one-pot s5mthesis of TMG including the hydrolysis of 2,2,5,5-tetramethyl-l,3-dioxolan-4-one, resulting in moderate 5deld [49-51%] of TMG. 

Substituents in the indazole ring may direct a given reaction towards another position either by their R and I electronic properties or simply by protecting the most reactive position. Examples of both types are found in sulfonation studies (67HC(22)l). As indicated before (Section 4.04.2.3.2(i)), sulfonation takes place at position 7. However, the presence of an amino group at positions 5 or 7 directs the attack towards the 4-position (Scheme 40). To obtain the indazole-5-sulfonic acid a more complicated procedure has been used but it is still based on the same ideas. 

Polymer supported reagents, catalysts, protecting groups, and mediators can be used in place of the corresponding small molecule materials (Sherrington, 1991 Sundell and Nasman, 1993). The reactive species is tightly bound to a macromolecular support which immobilizes it. This generally makes toxic, noxious, or corrosive materials much safer. The use of polystyrene sulfonic acid catalyst for the manufacture of methyl r-butyl... 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

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