Heterocyclic compounds synthesized from

The application of this methodology to suitably functionalized alkynes has allowed a direct and easy synthesis of important heterocyclic compounds starting from readily available substrates. New /1-lactone [100,101] and /3-lactam [102] derivatives were synthesized in good yields from a,a-disubstituted propynyl alcohols and amines, respectively (Eq. 38), through the mechanistic route shown in Scheme 18, path a. The substitution a to the triple bond was a necessary requisite for cychzation to occur, owing to the reactive rotamer effect [301]. 

Aniino4-methyl-5-phenylthiazole-3-oxide (353) was synthesized from the a-chlorooxime and Ba(SCN)2 (Scheme 202) (682). This class of compounds is usually prepared by such heterocyclizations (683). 

These consider ring syntheses from non-heterocyclic compounds first, followed by transformation of other heterocyclics. Syntheses in which no new heterocyclic ring is formed are dealt with primarily in the appropriate reactivity section, but with cross-referencing when necessary. Ring syntheses from acyclic precursors are dealt with as logically as possible according to the number and nature of the new ring bonds formed in the process. 

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

Syntheses from Acyclic Compounds and Other Heterocycles... 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

Highly substituted pyrrolo[l,2- ][l,2,4]triazines were synthesized from pyrrole derivatives, by closure of the triazine ring. Thus, hydrolytic cleavage of some 1,2-diaminopyrroles having a 1-NH-BOC-protected amino function 43 followed by reaction with 1,2-dicarbonyl compounds afforded a one-pot access to the corresponding bicyclic heterocycles 44 (BOC = f-butoxycarbonyl Equation 6) < 1997J(P 1)1829>. 

Moore and Willer reported the synthesis of some nitramine explosives containing a furazan ring fused to a piperazine ring. The tetranitramine (46) is synthesized from the condensation of 3,4-diaminofurazan (DAF) (24) with glyoxal under acidic conditions followed by A-nitration of the resulting heterocycle (45). The calculated performance for the tetranitramine (46) is very high but the compound proves to be unstable at room temperature. Instability is a common feature of heterocyclic nitramines derived from the nitration of aminal nitrogens. 

Other heterocyclic compourtds containing four sulfur atoms - tetrathiocines 196, 197 - were synthesized from activated aromatic compounds, in particular 1,2-dialkoxybenzenes or 2,3-dialkoxynaphthalenes, and sulfur monochloride in acetic acid in fairly good yields (1989PS111 Scheme 97). Biphenyl 154 treated with S2CI2 under the same conditions yielded 1,2-dithiines (see Section 4.3). 

In addition to the examples of coumarin syntheses given in the reviews mentioned above and in the treatise on heterocyclic compounds (B-51MI22400), more recent studies have made use of the Perkin synthesis. These include the use of substituted phenoxyacetic acids to prepare 3-phenoxycoumarins (78CI(L)628> and the synthesis of chlorocoumarins from chlorosalicylaldehydes (81T2613). The use of DBU in place of sodium acetate was necessary to effect the ring closure of a number of o-hydroxyketones (78BCJ1907). 

Dihalocyclopropanes containing all possible combinations of halogens have been synthesized. From the vantage point of the synthetic chemist, dibromo- and dichloro-cyclopropanes elicit the most useful and fascinating chemistry, and therefore this discussion will be centered around the formation and transformations of these two groups of compounds. For the sake of completeness, dihalocyclopropenes have been discussed where appropriate. To emphasize the synthetic potential, separate subsections are devoted to certain topics, e.g. formation of heterocycles. 

This section covers the synthesis of aziridines, oxiranes, /J-lactams and oxetanes. Aziridines are fairly important moieties in bioactive molecules and thus new routes for their synthesis are constantly being developed. /1-Lactams are probably the most important heterocyclic compounds that contain a single nitrogen atom, due to their importance in penicillin and cephalosporin chemistry. Their synthesis and chemistry has received much attention and much of this work has been reviewed544. The oxygen-containing heterocycles are much less commonly synthesized from double-bonded functional groups. 

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