Synthesis of phenylacetaldehyde amidines and their intramolecular cyclization (original) (raw)
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Heterocyclic Amidines: I. A One-Step Synthesis of New a-Substituted Imidazolylphenylacetic Acids
HETEROCYCLES, 1995
The reaction of a-phenyl-R-formylacrylic derivatives with various amidines (benzamidine, acetamidine) and heterocyclic amidines (2-aminopyridines, 3-aminopyridazines), yields asubstituted imidazolylphenylacetic acids and imidazo[l,2-xlazines bearing a phenylacetic acid residue in position 3. Some mechanistic aspects of the cyclocondensation reaction will be discussed. Within the scope of our current research on original benzodiazepine receptor ligands,l-3 we considered of special interest the synthesis of a series of 34a-phenyl ethoxycarbonylmethy1)imidazo[l,2-blpyridazines (14-18). The usual route for the preparation of 1,2-disubstituted imidazo[l,2-xlazines (1) involves the cyclocondensation of an heterocyclic amidine (2) with substituted halomethyl ketones (3) (R1 and R2 + H),4,5 as shown in Scheme 1. For the synthesis of 3-monosubstituted imidazole derivatives (1) (R1 = H, R2 t H), a corresponding substituted a-haloacetaldehyde would be needed in the same reaction pathway. Such compounds are generally unstable and, to our knowledge, only phenylbr~moacetaldeh~de has been used for building 3-phenylimidazo[l,2-xlazines (1) (R1= H, R2 = Ph)6. In addition, for the specific a-haloacetaldehyde (3a) (R1 = H, R2 = CH (Ph) COzEt), an amidine facilitated dehydrohalogenation leading to ethyl a-phenyl-&formylacrylate (4a) was observed. However the R-formylacrylate (4a) is a polyelectrophilic reagent, and may itself
Synthesis of cyclic enamides by intramolecular cyclization of acetylenic amides
Tetrahedron Letters, 1995
Cyclic enamides 12 of a type useful in the synthesis of naturally occurring chlorins, isobacteriochlorins, and corrins have been prepared by a process involving Nicholas-Schreiber condensation to afford acetylenic amides 13, followed by either n-Bu4NF-or LiAl(NHBn)4-catalyzed ring closure. In a recent series of papers we described an efficient synthesis of dihydropyrromethenones of general structure 4,1 which were prepared by a two step sequence involving Sonogashira coupling of acetylenic amides 1 with iodopyrroles 2, 2 followed by fluoride ion catalyzed 5-exo-dig cyclization (Scheme 1). Dihydropyrromethenones 4 are attractive precursors for biologically important linear tetrapyrroles such as phytochrome, phycocyanin, and phycoerythrin. 3 The utility of this approach stems partly from the fact that a wide variety of ring-A synthons 1 (and ent-1) are available by Nicholas-Schreiber reaction of chiral ester enolates with cobalt stabilized propargylic cations (vide infra, dashed line in 1, Scheme 1).1, 4 In addition, ring-B pyrroles of type 2 can be prepared on large scale with unequivocal control over regiochemistry.5
Tetrahedron, 2000
combination of amides and 2-pyridinesulfonyl chloride was evaluated as synthons of the dication C(R 1)±N(R 2) 2 21. When the substrates were primary amines, high yields of formamidines and amidines were obtained. When the substrates were a-aminoamides, a-aminonitriles were obtained. Through this process, naturally occurring a-aminoacids can be transformed into chiral a-aminonitriles with complete retention of stereochemical con®guration. All reactions proceed rapidly at room temperature, and normally ®nish within 10 min, with yields ranging from 80 to 95% for most cases. Among the sulfonyl chlorides examined, 2-pyridinesulfonyl chloride stands out in both reaction rate and selectivity of formamidine or amidine versus sulfonyl amide. The scope and limitations of the reaction among different types of amides as synthons and amines as substrates were examined.
A Convenient Catalyst-Free Synthesis of Some Substituted Pyridine Benzamides from Aryl Aldehydes
A new method of amides synthesis under catalyst-free condition has been developed by using aldehydes and aminopyridines. The amides were synthesized by using different aldehydes and aminopyridines using ethanol as a solvent and hydrogen peroxide as oxidant. The method helps in preparation of amides which were acquired in good yield within 4-5 h using conventional heating. The reaction is catalystfree. The developed method is easy, economical, and flexible.
Efficient synthesis of imidazole and pyrimidine derivatives
Chemistry of Heterocyclic Compounds, 2020
Amidines are known reagents in some synthetic methods for obtaining heterocyclic compounds as well as they are used as suitable reagents in numerous cycloaddition processes. An example of their application is the synthesis of pyrimidines and imidazoles shown by Vidal and coauthors. 1 Also, a new efficient and convenient approach was proposed to the synthesis of pyrimidines by Cu-catalyzed and 4-HO-TEMPO-mediated [3+3] annulation of commercially available amidines with saturated ketones. 2 On the other hand, diazaheterocyclic compounds are interesting from various scientific aspects 3 and have a significant potential as modern functional materials, 4 as well as they could be considered as objects which have a significant interest from the point of view of biological activity. 5 The aim of the work was to develop on the basis of known procedures 6 a method for the synthesis of N,N'-unsubstituted α-aminoamidines and ways for their further modification to synthesize new promising imidazole-and pyrimidine-containing compounds. We proposed and optimized a convenient and affordable pathway for the synthesis of previously undescribed α-aminoamidines 4a-e starting from N-protected amino-nitriles 1a-e, which can be easily obtained by described methods (Scheme 1). 7,8 The key stage of the approach is a procedure of hydrogenation of O-acetyl-substituted amino-oximes 3a-e in the presence of palladium catalyst. 9,10 It should be noted, that our attempts to perform direct reduction of aminooximes 2a-e to aminoamidines 4a-e were unsuccessful, though such transformations for amidines had been described in literature earlier. 11-16 Therefore, we carried out preliminary O-acylation of compounds 2a-e by acetic anhydride. A convenient and affordable synthetic pathway for obtaining new α-aminoamidines starting from aminonitriles is proposed. The α-aminoamidines obtained can be applied as substrates for further transformations and synthesis of imidazole-and pyrimidine-containing building blocks.
N,N-Dialkyl Amides as Versatile Synthons for Synthesis of Heterocycles and Acyclic Systems
Organic Synthesis - A Nascent Relook [Working Title]
N,N-Dialkyl amides such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), are common polar solvents, finds application as a multipurpose reagent in synthetic organic chemistry. They are cheap, readily available and versatile synthons that can be used in a variety of ways to generate different functional groups. In recent years, many publications showcasing, excellent and useful applications of N,N-dialkyl amides in amination (R-NMe 2), formylation (R-CHO), as a single carbon source (R-C), methylene group (R-CH 2), cyanation (R-CN), amidoalkylation (-R), aminocarbonylation (R-CONMe 2), carbonylation (R-CO) and heterocycle synthesis appeared. This chapter highlights important developments in the employment of N,N-dialkyl amides in the synthesis of heterocycles and functionalization of acyclic systems. Although some review articles covered the application of DMF and/or DMA in organic functional group transformations, there is no specialized review on their application in the synthesis of cyclic and acyclic systems.