Proton-transfer compounds with 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (sulfamethazine): the structures and hydrogen bonding in the salts with 5-nitrosalicylic acid and picric acid

Abstract

The structures of the anhydrous proton-transfer compounds of the sulfa drug sulfamethazine with 5-nitrosalicylic acid and picric acid, namely 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2-hydroxy-5-nitrobenzoate, C12H15N4O2S(+)·C7H4NO4(-), (I), and 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2,4,6-trinitrophenolate, C12H15N4O2S(+)·C6H2N3O7(-), (II), respectively, have been determined. In the asymmetric unit of (I), there are two independent but conformationally similar cation-anion heterodimer pairs which are formed through duplex intermolecular N(+)-H···O(carboxylate) and N-H···O(carboxylate) hydrogen-bond pairs, giving a cyclic motif [graph set R2(2)(8)]. These heterodimers form separate and different non-associated substructures through aniline N-H···O hydrogen bonds, one one-dimensional, involving carboxylate O-atom acceptors, the other two-dimensional, involving both carboxylate and hydroxy O-atom acceptors. The overall two-dimensional structure is stabilized by π-π interactions between the pyrimidinium ring and the 5-nitrosalicylate ring in both heterodimers [minimum ring-centroid separation = 3.4580 (8) Å]. For picrate (II), the cation-anion interaction involves a slightly asymmetric chelating N-H···O R2(1)(6) hydrogen-bonding association with the phenolate O atom, together with peripheral conjoint R1(2)(6) interactions between the same N-H groups and O atoms of the ortho-related nitro groups. An inter-unit amine N-H···O(sulfone) hydrogen bond gives one-dimensional chains which extend along a and inter-associate through π-π interactions between the pyrimidinium rings [centroid-centroid separation = 3.4752 (9) Å]. The two structures reported here now bring to a total of four the crystallographically characterized examples of proton-transfer salts of sulfamethazine with strong organic acids.

Pharmaceutical crystalline complexes of sulfamethazine with saccharin: same interaction site but different ionization states

“…The API discussed in this study is sulfamethazine (SMT), an antibacterial drug and growth promoter in food animals. 7 For this compound, some interesting topics have been discussed in recent years, including solubilization, 7 tautomerism, 7,8 various ionization states, [9][10][11][12] and so on. Up to now, many pharmaceutical cocrystals 7,[13][14][15][16][17][18][19] and organic salts 9-12 of SMT have been reported.…”

“…Up to now, many pharmaceutical cocrystals 7,[13][14][15][16][17][18][19] and organic salts 9-12 of SMT have been reported. In these crystalline complexes, SMT may exist in four different states: amidine tautomer 7,8,13-19 (Scheme 1a), imidine tautomer 7,8 (Scheme 1b), cationic [9][10][11] (Scheme 1c), or anionic form 12 (Scheme 1d).…”

Differences in Coformer Interactions of the 2,4-Diaminopyrimidines Pyrimethamine and Trimethoprim

“…In all cases, the carboxylic acid formed a pair of H bonds with the sulfonamide/N­(heterocycle) site of either the amidine or the imidine tautomer of smz . This R 2 2 (8) motif was also observed in the crystal structures of salts and cocrystals with benzoic acid, salicylic acid, anthranilic acid, 4-aminobenzoic acid, 4-aminosalicylic acid, acetylsalicylic acid, 2-nitrobenzoic acid, 4-nitrobenzoic acid, 2,4-dinitrobenzoic acid, indole-2-carboxylic acid, 4-chlorobenzoic acid, and 5-nitrosalicyclic acid . By contrast, stz/3,5-dinitrobenzoic acid, sulfamethoxazole/3,5-dinitrobenzoic acid, and sulfapyridine/2-chloro-4-nitrobenzoic acid all have different synthons .…”

“…71 This R 2 2 (8) motif was observed in the crystal structures of salts and cocrystals with benzoic acid, 72 salicylic acid, 73 anthranilic acid, 4-aminobenzoic acid, 74 4-aminosalicylic acid, acetylsalicylic acid, 75 2-nitrobenzoic acid, 76 4-nitrobenzoic acid, 77 2,4dinitrobenzoic acid, indole-2-carboxylic acid, 78 4-chlorobenzoic acid, 79 and 5-nitrosalicyclic acid. 80 By contrast, stz/3,5dinitrobenzoic acid, sulfamethoxazole/3,5-dinitrobenzoic acid, and sulfapyridine/2-chloro-4-nitrobenzoic acid all have different synthons. 70 In the stz•glutaric acid 81 and stz•4-nitrobenzoic acid 82 cocrystals, stz and the carboxylic acid both form homodimers.…”

Sweet Sulfamethazine Acesulfamate Crystals with Improved Compaction Property

“…Sulfamethazine (SMT, Figure a) is a sulfonamide antibacterial drug which is used to treat or prevent infections in both humans and animals, with a broad spectrum of activity against Gram-positive bacteria, Gram-negative bacteria, and some protozoa. , SMT can exist in two neutral tautomers, i.e., amidine − and imidine, ,, cation (protonation of the −NH 2 group, p K a,1 = 2.65), − and anion (deprotonation of the sulfonamide −NH– group, p K a,2 = 7.65) . Correspondingly, various organic salts and pharmaceutical cocrystals of SMT were prepared and characterized with a focus on crystal structures and solid–state properties. − Taste masking and compaction property enhancement of SMT are desired for developing high-quality oral tablet products because of its bitter taste . Additionally, our preliminary data suggest that SMT exhibit poor compaction properties.…”