Sulfonyl with amines

The sulfonyl chloride group is the cure site for CSM and determines the rate and state of cure along with the compound recipe. It is less stable than the Cl groups and therefore often determines the ceiling temperature for processing. The optimum level of sulfonyl chloride to provide a balance of cured properties and processibiUty is about 2 mol % or 1—1.5 wt % sulfur at 35% Cl. It also undergoes normal acid chloride reactions with amines, alcohols, etc, to make useful derivatives (17). 

An efficient method has been developed for the conversion of pyrimidine-2-thiol into the sulfonyl chloride 75, which was reacted in situ with amines. A modified method gave the rather more stable (and storable) sulfonyl fluoride 74 <06JOC1081>. 

Figure 9.16 Lissamine rhodamine B sulfonyl chloride reacts with amine-containing molecules to produce stable sulfonamide bonds.

A sulfonyl chloride group rapidly reacts with amines in the pH range of 9-10 to form stable sulfonamide bonds. Under these conditions, it also may react with tyrosine —OH groups, aliphatic alcohols, thiols, and histidine side chains. Conjugates of sulfonyl chlorides with sulf-hydryls and imidazole rings are unstable, while esters formed with alcohols are subject to nucleophilic displacement (Nillson and Mosbach, 1984 Scouten and Van der Tweel, 1984). The only stable derivative with proteins therefore is the sulfonamide, formed by reaction with e-lysine... 

The group of Caddick has described the synthesis of functionalized sulfonamides by microwave-assisted displacement of pentafluorophenyl (PFP) sulfonate esters with amines (Scheme 6.159) [306]. Their ease of handling due to their higher crystallinity, along with their long shelf-life and their ability to react under aqueous reaction conditions, makes these an attractive alternative to sulfonyl chlorides. The microwave-assisted reaction of alkyl PFP esters with amines is a facile process which proceeds cleanly and in good yields with a number of different amines, including primary, secondary, and sterically hindered amines, and anilines. Optimum condi-... 

The first examples were benzene disulfonimide derivatives prepared from o-benzenebis(sulfonyl chloride) or -disulfinic acid with amines or HNO2 respectively <84CHEC-I(6)914>, or benzothiazole derivatives (94) obtained from benzenesulfonamides or azides containing ortho SR or SOR groups... 

Sulfonylations of anions formed by deprotonation of azinones are not described in previous editions <1984CHEC(2)1, 1996CHEC-II(6)1>. 4,5-Dichloropyridazin-3(2//)-one is sulfonylated at N-2 with several benzenesulfonyl chlorides in the presence of a base <2002JHC203>. Reactions of the resulting compounds with amines yield sulfonamides (see Section 8.01.8.5). 

Oxidation of 2-thiopyrimidines 595 with sodium hypochlorite at —25°C has been used to prepare pyrimidine-2-sulfonyl chlorides 596 which were then reacted with amines in situ to prepare sulfonamides 597 <2006JOC1080>. Alternatively, reaction of the chlorides with KHF2 and a quaternary ammonium can be used to prepare sulfonyl fluorides, which are stable enough to isolate <2006JOC1080>. 

Enantioselective synthesis of /3-amino alcohols by Sml2-mediated cross-pinacol coupling of the planar chiral iV-sulfonyl(ferrocenylidene)amine with ferrocene carboxaldehyde is achieved by facile reduction of the ferrocenyli-dene amine with Sml2, followed by enantioselective addition to the aldehyde (Equation (75)). ... 

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 ... 

Alternatively, sulfonamides can also be prepared by oxidation of sulfinamides with periodate (Entry 3, Table 8.8) or with MCPBA [125]. Polystyrene-bound sulfonyl chlorides, which can be prepared from polystyrene-bound sulfonic acids by treatment with PCI5, SOCI2 [126-129], CISO3H [130], or SO2CI2/PPI13 [131], react smoothly with amines to yield the corresponding sulfonamides (Entry 4, Table 8.8). Support-bound carbamates of primary aliphatic or aromatic amines can be N-sulfonylated in the presence of strong bases, and can therefore be used as backbone amide linkers for sulfonamides (Entries 5 and 6, Table 8.8). 

Sulfonylation of amines can be a useful way of differentiating (chemically) between primary, secondary, and tertiary amines by what is known as the Hinsberg test. Primary and secondary amines both react with a sulfonyl chloride, but only the sulfonamide from the primary amines has an N—H hydrogen. The sulfonyl group makes this hydrogen relatively acidic and the sulfonamide therefore dissolves readily in sodium hydroxide solutions. The secondary amine does not give a base-soluble amide, whereas the tertiary amine gives no sulfonamide ... 

One approach to this problem is to start with the alkyl terminated surfaces and carry out chemical transformations of the methyl end group. Chidsey and co-workers employed this approach by forming sulfonyl chloride terminal groups via a photoinitiated free radical reaction of CI2 and SO2 with the original methyl-terminated monolayer [45]. These were then converted to sulfonamides by reaction with amines. Schematically this two-step reaction scheme can be written as ... 

Other nucleophiles have been used in this reaction. For example, BINAP was shown to be the best ligand for the enantioselective allylic amination of 19 with sodium diformylamide, a protected ammonia equivalent, furnishing the desired product in good yield and excellent enantioselectivity [96]. Also, a P,N-ligand has been developed for the allylic sulfonylation with good ee but moderate yield [97]. 

On reaction with amines R NHR, only the AE (reaction sequence A) with C—O bond scission will lead to amination product 37 and sulfonic acid 38, whereas the competing attack on the sulfonyl group (reaction sequence B) with S—O bond scission will lead to 2-(l//)-pyridinone (27) and a sulfonamide 39, thus decreasing the yield of the desired amination product (cf. 209 210 in Section IV,E). This B-type of scission is also... 

Some of these transformations were accompanied by additional reactions, e.g. formylation of the aromatic or heteroaromatic - nucleus or CH-acidic methyl groups further dehydration of amides to nitriles was observed. Adducts from amides and PCI3, sulfonyl halides or SO2CI2/SCXZI2 from which amidines can be obtained by reaction with amine derivatives (compare Section 2.7.2.5 and refs. 5 and 14) have not found wide application for this purpose. An interesting reaction is the preparation of the amidine (294 equation 158) from 7V-pentafluorophenylformamide. By thermal decomposition of the adducts from secondary amides and 7V,iV-dialkylcarbamoyl chlorides amidinium salts were synthesized from which the amidines (295 equation 159) were set free by treatment with bases. " ... 

During the last years the reaction of 0-sulfonylated oximes with amines was applied repeatedly.It gives diaziridines even from electron-poor carbonyl compounds, which had not been accessible so far. For example, diaziridine 91 is obtained from the 0-tosyl oxime of mesoxalic ester (90). ... 

Other useful syntheses of 1,2,3-triazoles include diazo-transfer to enamino-ketones from either sulfonyl azides or S-diazo-oxindole, " and reaction of dichloroacetaldehyde tosylhydrazone with amines, and each of these is illustrated below. ... 

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