Arylamine sulfonamides

There are examples of nucleophilic displacement of halide from halo-1,2,5-thiadiazoles by ammonia, primary alkylamines, secondary alkylamines, arylamines, sulfonamides, and phthalimide <1984CHEC(6)513, 1996CHEC-II(4)355>, but the reactions often require high temperatures and excess of the nucleophile. 

The classic syntheses of the antibacterial sulfonamides involve reaction of the appropriate arylamine with an acid addition salt of p-amino-benzenesulfonyl chloride, or p-nitrobenzenesulfonyl chloride followed by reduction. Chemical interest largely resides in preparation of the corresponding arylamines. For the synthesis of sulfacytine (134), N-ethyl uracil (131) was converted to its thioamide (132) by reaction with phosphorous pentasulfide. The newly introduced sulfur is then displaced with ammonia in methanol to give 133. Standard reactions complete... 

Acetyltransferases catalyze the acetylation of amino, hydroxyl, and thiol functional groups. Acetylation of hydroxy and thiol groups is comparatively rare and of much less importance in alkaloid metabolism than reactions with amino functional groups. The types of amines that are acetylated include arylamines (the major route of metabolism in many species), aliphatic amines, hydrazines, sulfonamides, and the a-amino group of cysteine conjugates. The purification, physical properties, and specificity of the N-acetyltransfereases have been reviewed (116-118). 

The antibacterial sulfonamide phthalazole 268 is obtained free of imide and bisamide side products (that occur upon reaction in solution or in the melt) if stoichiometric solid-state milling of the reactants 266 and 267 is performed for the acylation [95] (Scheme 38). Numerous solid arylamines and heterocyclic amines react correspondingly with phthalic anhydride upon stoichiometric milling and provide 100% yield without any workup requirement [22]. 

The aqueous acidic hydrolysis of carbazolesulfonic acids has been studied their resistance to hydrolysis increases with the number of sulfonic acid groups on the nucleus, thus 3,6-di- < 1,3,6-tri- < 1,3,6,8-tetrasulfonic acids in terms of stability to aqueous acid. It was also demonstrated that 2,7-di- > 3,6-di- > 1,6-disulfonic acids in terms of lability. Carbazole sul-fonyl chlorides form sulfonamides with arylamines. ... 

An improved method for the well-know preparation of pyrroles from 2,5-dimethoxy-tetrahydrofuran was reported. Alkyl and arylamines, amides and sulfonamides were condensed by using P,0, in dry toluene. <95SCl857>... 

The palladium-catalyzed formation of diarylamines has been used in several contexts to form molecules of biological relevance. The ability to prepare haloarenes selectively by an ortfio-metalation-halogenation sequence allows the selective delivery of an amino group to a substituted aromatic structure. Snieckus has used directed metalation to form aryl halides that were subsequently allowed to react with anilines to form diarylamines (Eq. (34)) [209]. Frost and Mendonqa have reported an iterative strategy to prepare, by the palladium-catalyzed chemistry, amides and sulfonamides that may act as peptidomimetics. Diaryl-amine units were constructed using the DPPF-ligated palladium catalysts, and the products were then acylated or sulfonated with 4-bromobenzoyl or arylsulfonyl chlorides [210]. Le-miere has coupled primary arylamines with 4-chloro-3(2H)-pyridazinones to form compounds with possible analgesic and antiinflammatory properties. 

C.4).- -7o Arylamines and sulfonamides are usually aminomethylatcd in the para position (2l5byC) the sulfonamides, in particular, arc unreacti ve when the H atom of NH— SO2 is replaced by an alkyl group. 

The immunogenicity of sulfonamide antimicrobials may be due to the presence of an arylamine group at the N4 position of the sulfonamide molecule. Thus, allergic crossreactions between different sulfonamides can occur. Therefore, in cases of known hypersusceptibility to a specific sulfonamide exposure to other sulfonamides should be avoided. Cross-reactions can even occur with para-aminosalicylic acid and local anesthetics of the procaine type however, the real frequency of these cross-sensitivities is not known and their significance is undetermined. It should be noted that as many as 50% of... 

Studies with additional substrates for NAT demonstrated that the phenotype was not relevant to all substrates. For example, the NAT phenotype was clearly recognized for arylamines such as isoniazid, some sulfonamides, amrinone, dapsone, procainamide, caffeine, and clonazepam. The phenotype was not observed with other arylamine substrates such as p-aminobenzoate (PABA) and p-aminosahcylate (PAS). A folate catabolite, p-aminobenzoylglutamate, is the only endogenous NAT substrate proposed. Flowever, NAT2 knock-out and NATl and NAT2 double knock-out mice do not express phenotypical abnormalities, suggesting that these enzymes are not required for development or function. ... 

Addition reactions. With InBra as catalyst sulfonamides are induced to add to unactivated alkenes in refluxing toluene. Carbamates and arylamines do not react in the same way. 

Arylamine N-acetyltransferases (NAT) are highly conserved in eukaryotes. These cytosolic enzymes transfer acetate from acetylCoA to primary amines, hydrazines, sulfonamides, and aromatic amines. They are 30 to 34 kDa in size. Humans express two functional NATs, NATl and NAT2. The genes for both isoforms encode 290 amino acids, and are found on chromosome 8. Their nucleotide sequences share 87% homology. These enzymes exhibit polymorphism, and allelic variation especially for NAT2 is associated with fast and slow acetylator phenotypes. 

Synthesis of Sulfonamides. Sulfonamides are formed in moderate to good yields by the reaction of methoxycarbonylmethanesulfonyl chloride with the desired amine in the presence of triethylamine (eq 2). This reaction is usually carried out using arylamines, but can be extended to peptidic amines. ... 

In 2015, Xiao and co-workers reported an iridium complex (14)-catalyzed N-alkylation of amines with alcohols under mild conditions (100 °C) (Scheme 22) [113]. Anilines, heteroarylamines, A -alkyl-A(-arylamines, and sulfonamides could serve as A-nucleophiles. The same method can also be applied to amine-based N-... 

The other advantage of aminocarbonylation involves the great variety of nucleophiles that can effectively be applied as reactants. Beside the commonly used primary and secondary amines, these include propargylamine in the synthesis of an intermediate of 8-epi-griseoviridin [105], arylamines, and heteroarylamines in the synthesis of gonadotropine-releasing hormone antagonists [104], substituted hydrazine derivatives [97], hydrazides [98], amino crown ethers [99], and amino acids [94,106]. Even sulfonamides were shown to be able to participate as nucleophiles in microwave-accelerated carbonylation in the presence of Mo(CO)g as the carbonyl source [107]. 

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