Heterocyclcs

Keywords 1,3,2-diazaphospholes 1,3,2-diazaphospholenes 1,3,2-diazaphosphinines 2,3-dihydro-l,3,2-diazaphosplinines diketiminto-phosphenium ions N-heterocyclic phosphines N-heterocyclc phosphenium ions 1,2,3-diazaphospholenium ions... 

PE. Evans u. A.B. Holmes, Tetrahedron 47, 9131-9166 (1991) Medium-Ring Nitrogen Heterocyclcs" (Azepines, Azocines, Azonines, and Derivatives). 

Tetrahydrofuranes.1 An example of a new route to these heterocyclcs is formulated in equation (I). Cyclization with acid alone is effected in only about 30%... 

Pyridine is a rc-electron-deficient heterocyclc. Due to the electronegativity of the nitrogen atom, the a and y positions bear a partial positive charge, making the C(2), C(4), and C(6) positions prone to nucleophilic attacks. A similar trend occurs in the context of palladium chemistry. The a and y positions of halopyridines are more susceptible to the oxidative addition to Pd(0) relative to simple carbocyclic aryl halides. Even a- and y-chloropyridines are viable electrophilic substrates for Pd-catalyzed reactions under standard conditions. 

Some oxidations of heterocyclcs with two heteroatoms proceed very readily. Thus, fluorinated quinazoline is oxidized to quinazol-4-one on fusing for only 2 minutes (Table 16).264 On the other hand, more vigorous oxidation of 5-fluoro-l,3-dimethyluracil by 3-chloroperoxybenzoic acid leads to the formation of unstable intermediate radicals that tend to rearrange to 4-hy-droxy-l,3-dimethylimidazoledione 3-chlorobenzoate (Table 16), similar177 to the chemical behavior of trifluoromethylated phenol.265... 

In various heterocyclic compounds two types of C F bonds are hydrogenolyzed. In fluoromethyl groups, which are attached to the aromatic heterocyclic ring, the C-F bonds arc activated similarly to benzylic C-F bonds, but the degree of activation is influenced by the position relative to the heteroatom the reactivity of aromatic C-F bonds in six-membered heterocyclcs is strongly influenced by their positions relative to the heteroatom(s). 

To a solution of intermediate 8 (1.00 g, 3.03 mmol) in anhyd THF (10 mL) was added, under a N2 atmosphere, NaH (109 mg, 4.54 mmol) in one portion. After stirring for 5 min, the suspension was heated at reflux for 1 h and then allowed to cool to rt. The mixture was poured into HzO (30 mL) whereupon a solid formed. After 5 min, filtration gave a solid, which was washed with H,0 (2mL) and dried under full vacuum for 1 h. A white solid (805 mg) was obtained. The aqueous filtrate was extracted with C HC13 (3 x 10 mL), and the organic layers were dried (Na2S04.) and concentrated to yield a further 91 mg of the crude product. The combined material was further purified by recrystallization [CHCI, (13.2 mL)/hexane (8 tnL)] to give heterocyclc 9 as a colorless solid yield 574 mg (61 %) mp 240.5-243.5 C. 

Having been generated, these moieties undergo cyclization reactions providing efficient synthetic routes to /V-heterocyclcs with a variety of ring sizes. Thus, direct irradiation of secondary aminoethyl and aminopropyl stilbenes leads to benzazepines in improved yields (Hintz et al. 1996). As known, benzazepines are used in medicine as antidepressants. Scheme 6-37 illustrates ion radical cyclization with the formation of the benzazepine derivative (65% yield). 

K. Undheim and T. Benneche, Metalation and metal-assisted bond formation in it-electron deficient heterocyclcs, Acta Chem. Scand. 1993, 47, 102-121. 

Complications may however arise in this type of synthesis, besides the rcgioselec-tivity involved in the cyclization step, due mainly to the possibility of cleavage of the bond linking the heterocyclc ring to the benzylic carbon atom during the formation of the methyleneimmonium ion. In this way, rupture of the molecule, heterocyclic ring enlargement (sec Fig. 69, Chap. I), and the abovementioned racemization" may take place. 

Flame retardants—Whereas halogen-containing Mannich bases arc mainly used as modifiers of macromolccular materials, as mentioned before, phosphorus derivatives arc employed as additives. These products arc obtained from phosphorous acid or phosphites 584 " and from other analogous phosphorus-containing compounds. N-Heterocyclcs, after reaction with melamine and formaldehyde (585), are also used as (lame retardants. -... 

Intramolecular nucleophilic substitution reactions of chlorine " " or bromine with alco-holates lead to tetrahydropyrans. The alcoholate can be formed in situ by deprotccting an alcohol.Activated aromatic chlorides give in nucleophilic aromatic substitution reactions a six-membered heterocyclc, e.g, reaction of 1 to give 2. ... 

The N-analogs1 8 of the Cope and Claisen rearrangement have been widely used for syntheses of amines and /V-heterocyclcs, for example, the l,l -diaza-Cope rearrangement is the key step in the Fischer indole synthesis. 

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