Sulfadiazine is a short-acting sulfonamide. It is readily absorbed from the gastrointestinal tract and rapidly excreted by the kidney. As with other sulfonamides, there are few specific indications because of the wide range of safer and more effective alternative antibiotics. In addition, the emergence of resistance to the sulfonamides has rendered this drug class unsuitable for the treatment of many infections that responded to them in the past. Sulfadiazine is used Sulfad to treat urinary tract infections and as an adjunct for the treatment of a few parasitic diseases. Although sulfadiazine, like other sulfonamides, is fairly well tolerated, its use is associated with adverse effects. Hypersensitivity reactions and gastrointestinal upset are among the common side effects associated with sulfadiazine.


Fundamentals: Ligands, Complexes, Synthesis, Purification, and Structure

Z. Xu, L.K. Thompson, in Comprehensive Coordination Chemistry II, 2003


1.5.2.1 Overview

Diazine (N–N) bridge-containing ligands are of fundamental interest. From the magnetochemistry point of view, diazine (N–N) bridges in some conjugated aromatic heterocyclic ligands can bring two metal, e.g., copper(II) centers, into close proximity to form dinuclear complexes, and generate intramolecular magnetic exchange between the metal centers via the π system of the heterocyclic ligand. This varies with the nature of the diazine ligands. Extensive studies have revealed that in the dinuclear copper(II) complexes involving pyrazine, pyrimidine, and other related bridges, where the heterocyclic nitrogen donor centers are arranged at the 1,4 or 1,3 ring positions, weak intramolecular antiferromagnetic interactions are usually observed. However, for some heterocyclic diazine ligands with a 1,2-heterocyclic nitrogen arrangement, moderate to strong antiferromagnetic coupling is observed depending on the identity of the ligand.1,17–62 Several types of 1,2-aromatic diazine-derived ligands have been investigated and their ability to propagate magnetic coupling highlighted. Among them, pyridazine and phthalazine ligands provide the best platform for magnetic interactions, which are normally antiferromagnetic, e.g., for copper(II) (but not always). Due to the unique features for providing effective electronic superexchange pathways, a substantial number of pyridazine- and phthalazine-derived ligands have been developed since the 1970s. In this section, the synthetic chemistry of pyridazine and phthalazine ligands will mainly be discussed, and a brief coordination chemistry of these ligands will also be covered.


Fundamentals: Ligands, Complexes, Synthesis, Purification, and Structure

S. Swavey, K.J. Brewer, in Comprehensive Coordination Chemistry II, 2003


1.9.3.3 Diazines and Polyazines

Diazines are heterocyclic dinitrogen aromatic rings. They are better π-acceptor ligands than pyridine, function as bridging ligands, and lead to π-mediated metal–metal interactions.21 Pyrazine (7) is one of the more widely studied monodentate bridging ligands and has been used to bridge a variety of transition metals22 including Pt,23 Mo,24 and Ru25. Typically, the two metals bridged by pyrazine will be coplanar with the pyrazine ring, providing significant electronic coupling.16,26,27 Pyrimidine (8) and pyridazine (9) are also used as bridging ligands. Diazines function to bring two metal centers into close proximity providing coupling through a conjugated ring system.


Although not as strong a π-acceptor as the other two diazines pyrimidine (8) is still stronger than pyridine28 and has been used to bridge Ru21 and Pt29. Stable bridged complexes of pyridazine (9) are rare.30–32


Polyazines like triazine (10) and tetrazine (11) have not been as thoroughly studied as the diazines, however, they make up an important part of the azine literature.1 Triazine has been used to bridge three platinum(II) metals and the X-ray structure of this triplatinum complex has been described.29 In this complex it was determined that coordination at one nitrogen does not significantly affect the donor capacity of the other two nitrogen atoms. The tetrazine ligand by itself is unstable but has been successfully used to bridge ruthenium(II) and iron(II) phthalocyanines.33



Sign in to download full-size image

Sulfonamides, quinolones, antiseptics, and disinfectants

Suman Rohilla, Deepika Sharma, in Medicinal Chemistry of Chemotherapeutic Agents, 2023


2.1.2.6.4 Synthesis of sulfadiazine

Sulfadiazine in combination with pyrimethamine is the most effective treatment choice for toxoplasmosis. Most commonly employed method of synthesis of sulfadiazine involves reaction between 4-acetamidobenzene sulfonyl chloride and 2-aminopyrimidine, which results in formation of N-(4-(N-(pyrimidin-2-yl)sulfamoyl)phenyl)acetamide. 4-Acetamidobenzene sulfonyl chloride is obtained from treatment of acetanilide with chlorosulfonic acid. Further hydrolysis of N-(4-(N-(pyrimidin-2-yl)sulfamoyl)phenyl)acetamide removes acetyl group from para-amino functionality to yield sulfadiazine (Fig. 2.10) [30].



Sign in to download full-size image

Figure 2.10. Synthesis of sulfadiazine.


Antimicrobial Drugs

R.S. Vardanyan, V.J. Hruby, in Synthesis of Essential Drugs, 2006


Sulfadiazine

Sulfadiazine, N1-2-pyrimidinylsulfanilamide (33.1.7), is synthesized by reacting 4-acetylaminobenzenesulfonyl chloride with 2-aminopyrimidine, which gives an acetanilide derivative (33.1.6). The subsequent hydrolysis of this product with a base leads to the formation of the desired sulfadiazine [5–8].



Sign in to download full-size image

Like sulfacytine, this drug is effective for infections caused by streptococci, gonococci, pneumococci, staphylococci as well as colon bacillus. Sulfadiazine is used for pneumonia, cerebral meningitis, staphylococcal and streptococcal sepsis, and other infectious diseases, although it is the drug of choice for nocardiosis. This drug is not recommended for urinary tract infections because of its low solubility and certain nephrotoxicity. Synonyms of this drug are flammazine, sterinor, terfonil, and others.

It is used in the form of silver salts (sulfadiazine silver) as an external antibacterial agent, primarily for treating burns. It is believed that the presence of the silver ion in the molecule facilitates increased antimicrobial and wound-healing action.


Six-membered Rings with Three or more Heteroatoms, and their Fused Carbocyclic Derivatives

G.W. Morrow, in Comprehensive Heterocyclic Chemistry III, 2008


9.06.1 Introduction

1-Oxa-2,5-diazines and 1-thia-2,5-diazines 1–4 and their benzo analogs 5 and 6 remain relatively obscure heterocyclic systems. While 1-oxa-2,5-diazinanes 1 and 5,6-dihydro-4H-1-oxa-2,5-diazines 2 continue to appear in recent studies, 4H-1-oxa-2,5-diazines 3 remain unknown. Several examples of the previously elusive 6H-1-oxa-2,5-diazine system 4 as well as a number of synthetic studies leading to 1-H-benzo-1-thia-2,5-diazines 6 have now been reported (Figure 1) and will be examined in this chapter. Additional information on these systems is available in Chapter 6.15 in CHEC-II(1996) <1995CHEC-II(6)681>, though the corresponding section in CHEC(1984) contains limited information on the 1-oxa-2,5-diazines and none on 1-thia-2,5-diazines <1984CHEC(3)1039>.



Sign in to download full-size image

Figure 1.


Fused Five- and Six-membered Rings without Ring Junction Heteroatoms

Stephen P. Stanforth, in Comprehensive Heterocyclic Chemistry II, 1996


7.15.10.1.2 Intramolecular reactions

Diazine (399) undergoes an intramolecular Diels–Alder reaction (195 °C, 135 h) yielding the intermediate (400) which fragments giving a mixture of the isomeric pyranopyridines (401) (40% yield) and (402) (22% yield) (Scheme 8) 〈89T6211〉. In the presence of TFA this reaction proceeds at 72 °C and gives heterocycle (402) (85% yield) 〈89T6519〉.



Sign in to download full-size image

Scheme 8.


Triazine (403) gives the naphthyridone derivative (404) (95% yield) in diphenyl ether under reflux 〈90CZ381〉. Triazines (405; R1, R2 = alkyl, aryl) give tetrahydropyranopyridines (406) in good yield at 200 °C 〈87T5145〉 and triazine (407) gives heterocycle (408) (30% yield) when heated in diphenyl ether 〈92AP(325)349〉. When triazine (409) is heated (64 h) in bromobenzene at reflux, the thiopyranopyridine derivative (410) (57% yield) is obtained 〈89JOC4984〉. The sulfone derivative (411) gives an excellent yield (99%) of the corresponding product (412) after 12 h at reflux in bromobenzene but, in contrast, the sulfoxide (413) gives only a trace of product (414). Salt (415) gives the tetrahydrothiopyranopyridine derivative (416) (40% yield) in dioxane at reflux 〈89T6499〉.

মন্তব্যসমূহ

একটি মন্তব্য পোস্ট করুন

এই ব্লগটি থেকে জনপ্রিয় পোস্টগুলি

Sulfad

ছবি
  The structure of 2,4-(4′-aminobenzenamine)pyrimidine (1), a pyrimidine alkaloid previously isolated from the bulbs of Scilla madeirensis (Asparagaceae, synonym Autonoë madeirensis), has been revised. These conclusions were met via comparison of reported NMR and EIMS data with those obtained from synthetic standards. The Sulfad structure is the antibiotic sulfadiazine (2), which has likely been isolated as a contaminant from the site of collection. The reported bioactivity of 1 as an α1-adrenoceptor antagonist should instead be ascribed to sulfadiazine. Our findings appear to show another example of an anthropogenic contaminant being identified as a natural product and emphasize the importance of considering the biosynthetic origins of isolated compounds within a phylogenetic context. The reported isolation of the analgesic tramadol from the roots of the African medicinal plant Nauclea latifolia Sm. (Rubiaceae) in 2013 (1) garnered substantial attention from the scientific communi...
আরও পড়ুন

Sulfad

ছবি
  Sulfadiazine is a short-acting sulfonamide. It is readily absorbed from the gastrointestinal tract and rapidly excreted by the kidney. As with other sulfonamides, there are few specific indications because of the wide range of safer and more effective alternative antibiotics. In addition, the emergence of resistance to the sulfonamides has rendered this drug class unsuitable for the treatment of many infections that responded to them in the past. Sulfadiazine is used Sulfad to treat urinary tract infections and as an adjunct for the treatment of a few parasitic diseases. Although sulfadiazine, like other sulfonamides, is fairly well tolerated, its use is associated with adverse effects. Hypersensitivity reactions and gastrointestinal upset are among the common side effects associated with sulfadiazine. Fundamentals: Ligands, Complexes, Synthesis, Purification, and Structure Z. Xu, L.K. Thompson, in Comprehensive Coordination Chemistry II, 2003 1.5.2.1 Overview Diazine (N–N) brid...
আরও পড়ুন

Sulfad

ছবি
  Sulfadiazine is a short-acting sulfonamide. It is readily absorbed from the gastrointestinal tract and rapidly excreted by the kidney. As with other sulfonamides, there are few specific indications because of the wide range of safer and more effective alternative antibiotics. In addition, the emergence of resistance to the sulfonamides has rendered this drug class unsuitable for the treatment of many infections that responded to them in the past. Sulfadiazine is used Sulfad to treat urinary tract infections and as an adjunct for the treatment of a few parasitic diseases. Although sulfadiazine, like other sulfonamides, is fairly well tolerated, its use is associated with adverse effects. Hypersensitivity reactions and gastrointestinal upset are among the common side effects associated with sulfadiazine. Fundamentals: Ligands, Complexes, Synthesis, Purification, and Structure Z. Xu, L.K. Thompson, in Comprehensive Coordination Chemistry II, 2003 1.5.2.1 Overview Diazine (N–N) brid...
আরও পড়ুন