Heterocycles halogenated

An 8000-member library of trisamino- and aminooxy-l,3,5-triazines has been prepared by use of highly effective, microwave-assisted nucleophilic substitution of polypropylene (PP) or cellulose membrane-bound monochlorotriazines. The key step relied on the microwave-promoted substitution of the chlorine atom in monochlorotriazines (Scheme 12.7) [35]. Whereas the conventional procedure required relatively harsh conditions such as 80 °C for 5 h or very long reaction times (4 days), all substitution reactions were found to proceed within 6 min, with both amines and solutions of cesium salts of phenols, and use of microwave irradiation in a domestic oven under atmospheric reaction conditions. The reactions were conducted by applying a SPOT-synthesis technique [36] on 18 x 26 cm cellulose membranes leading to a spatially addressed parallel assembly of the desired triazines after cleavage with TFA vapor. This concept was later also extended to other halogenated heterocycles, such as 2,4,6-trichloropyrimidine, 4,6-dichloro-5-nitropyrimidine, and 2,6,8-trichloro-7-methylpurine, and applied to the synthesis of macrocyclic peptidomimetics [37]. 

Analogous reactions with bromoform produces the corresponding 3-bromo derivatives [6], while the reaction of alkylindoles with chlorofluorocarbene produces a complex mixture of halogenated heterocycles (Table 7.18) [9]. 

Due to its stability and water-solubility sodium tetraphenylborate is a particularly convenient starting material for such reactions. Several halogenated heterocycles were phenylated with NaBPlu in aqueous solution with [Pd(OAc)2] catalyst under microwave irradiation (Scheme 6.13) [36]. All reactions were mn under argon in Teflon-closed pressure tubes. It is not easy to compare these results to those of thermal reactions, since the temperature of the irradiated samples is not known precisely. Nevertheless, the microwave method is certainly very effective since 8-12 min irradiation at 100-160 W power allowed the isolation of 60-85 % phenylated products. 

No attempt will be made in this chapter to cover methods of preparation of halogenated heterocycles where the halogen is introduced before the ring is formed. 

Allenes have the 1,2-diene structure (I), where R1, R2, R3, R4 = H, alkyl, aryl, halogen, heterocyclic, ether, etc. Since the terminal methylene groups lie... 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

Halogenated heterocycles (2-, 3-, 4-bromopyridines, 2-chloro-3-bromoquinolines, 2-chloropyrimidine) react with anion 163a. The substitution products then undergo oxidative decyanation under phase-transfer catalytic conditions to afford phenyl hetaryl ketones in good yield (33-77%) (equation 109)202. 

Later in this volume. Chapter 18 presents a discussion of the electrochemical behavior of heterocyclic species. However, it is appropriate here to offer a short summary of the reduction of carbon-halogen bonds found in several classes of heterocyclic compounds. Many halogenated heterocyclic substances display behavior similar to that of aryl halides the carbon-halogen bond is reductively cleaved in a process involving two electrons and a proton to give a hydrogenated product. 

When an organolithium compound reacts with an organic halide the product is usually a hydrocarbon, reaction being analogous to a Wurtz-Fittig synthesis. However, the action of alkyl- or aryl-lithiums replaces the halogen by lithium in several halogenated heterocycles, aromatic ethers, and alkyl... 

Figure 7.22 PerfluoroaUcylation of halogenated heterocyclic compounds using RpC(0)0Na/ Cul system.

A novel concept for the synthesis of macrocyclic peptidomimetics 262, which incorporate heteroaromatic units, was reported (Scheme 39). This method involves sequential SNAr reactions of orthogonally protected amino groups of peptides and other linear oligomers on halogenated heterocycles such as 2,4,6-trichloro[l,3,5]triazines. The scope of this novel solid-phase approach was evaluated systematically by means of the SPOT-synthesis methodology on planar cellulose membranes <2000JC0361>. 

Position-flexible elaboration of halogenated heterocycles into metalated spedes as key intermediates for s5mthesis 07SL3096. 

Both systemic herbicides halosulfuron-methyl (101 maize, 18-35 g-a.i. ha ) [192] and imazosulfuron (102 paddy rice, 75-95 g-a.i. ha ) [193] demonstrate the structural variability of ring A, e.g., by incorporation of further halogenated heterocyclic systems such as 3-Cl,4-COOMe-l-CH3-lH-pyrazol-5-yl (101) and 2-chloroimidazo[l,2-a]pyridine-3-yl (102) (Fig. 35.24). 

Synthetic methods for the hydrodehalogenation of halogenated heterocycles 12COC2921. 

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