By Ring Formation

The exocyclic a,jS-unsaturated moiety of 4-arylmethylidenepyrazol-3-ones 438a,b 

3-ones 442 with mercaptoacetic acid or 2-mercaptopropionic acid and obtained the 

3- (pyrazol-4-yl)-2-arylthiazolidin-4-ones 444 in 50-82% yields. The reaction occurs via the adduct 443 which cyclocondenses to the product. 

4- [(3-oxopyrazol-4-yl)(phenyl)methyl]pyrazol-3-one 446, 3-[(3-oxopyrazol-4-yl)phe-nylmethyl]-benzo[b][l, 4]diazepin-2-one 447, 5-[(3-oxopyrazol-4-yl)phenylmethyl]-2-thioxopyrimidin-4-one 448 and 4-[(3-oxopyrazol-4-yl)(phenyl)methyl]isoxazol-5-one 449, respectively, in moderate to good yields. 

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The stereoisomers 16c and 16d have also been prepared by a [3 + 3]-type annelation between a,a -dimethoxylated amides and allyltrimethylsilane (363). Compound 366 was synthesized by ring formation with 363 and 365, prepared by methoxymethylation of 364, in the presence of TiCl4. Hydrogenation of 366 foWov/ed by bulylalion with n-BuLi and reduction with sodium borohy dride gave a mixture of stereoisomers 16c and 16d (Scheme 41) (437). 

Another example is the synthesis of (5R)-1-azabicyclo[3.3.1]nonan-2-one which involves a resolution step followed by ring formation. The bicyclic structure in the product inhibits a planar arrangement of the substituents around the amide nitrogen. The configuration at nitrogen is determined by the configuration at C-5. Thus, only the absolute configuration at C-5 had to be established (see p 438)47-48. 

Stabilization and Termination of Chain Growth by Ring Formation... 

Some bright blue direct dyes with good lightfastness are sulfonated dioxazine compounds, mostly synthesized by condensation of chloranil with amines followed by ring formation and sulfonation, e.g.,C.7. Direct Blue 106,51300 [6527-70-4] (14). 

A five-membered ring in a heterocyclic system is also formed by photocyclization of 2-(l-naphthylamino)-3,5-dichloropyridine (197)550. Cyclization can occur at the ortho or peri position of the naphthalene ring, but irradiation in aqueous tert-buty alcohol provided only 8-chlorobenz[( -a-carboline (198), formed by ring formation at the ortho position (equation 145). 

Over the last decade, a wide variety of functionalized phospholes have heen synthesized either directly by ring formation or via modification of preformed phosphole skeletons, as illustrated in Sections 3.15.9 and 3.15.10, respectively. Here, the stmctures of the previously descrihed derivatives are presented in tabular form along with their precursors, the schemes in which their synthesis is descrihed, and the references. Note that only isolated and fully characterized derivatives have heen included. 

Table IV shows compounds which were of interest because of their anti-schistosomiasis effect. In all these compounds paramethylaniline is a common structural unit, and we believe that activity depends on transport to a site of metabolism, where hydroxylation of the methyl group occurs. An electronegative group ortho to the methyl is necessary for activity, as is an aminoalkyl side chain. In Compounds 1 and 3 this side chain is fixed in its position by ring formation alternatively, the chain may be conformationally less rigid, as in Compounds 2 and 4. Log F measurements show that additivity principles do hold for all of these compounds and also suggest that an optimum log F exists this log P0 is about 4.0, as in Compounds 1 and 2 which are the most active. Compound 3 is too lipophilic, and 4 is not lipophilic enough both are less active than 1 and 2. It would seem that either a chloro or a nitro group would activate the methyl to hydroxylation differences in activity between chloro and nitro derivatives are the result of different w effects of these groups on transport.

The Oxoadd Chain Elongation Process Decarboxylation as a Driving Force in Biosynthesis Stabilization and Termination of Chain Growth by Ring Formation... 

Oxygen heterocycles. The dicyanocyclopropane derivative 95 has been obtained from 10 and bromofuranone 94, through Michael addition followed by ring formation . When dithiophenyl-substituted benzophenone 96 was reacted with 10 with catalysis of titanium... 

The tetrahydro-1,2-oxazepine (42) can be prepared from the chloroketone (41) by initial formation of the oxime, followed by ring formation. The oxazepine (42) can be converted into the crystalline (m.p. 142-143 °C) oxaiminium salt (43) on treatment with Meerwein s salt, and hence to the chemically unstable tetrahydro derivative (44) (Scheme 4) <83LA897>. 

An atom economic route for the preparation of fludioxonil (2) has been patented [18]. Known 2,2-difluorobenzodioxole 12 is regioselectively lithiated to form 13 (Scheme 15.2.3). In a one-pot reaction intermediate 13 is directly quenched with 14 followed by conversion of the formed intermediate 15 with TosMIC into the desired fludioxonil (2). Alternatively intermediate 13 can be quenched with DMF to form aldehyde 16 which is, similar to the above process, stepwise reacted with a cyanoacetic acid derivative to obtain 15 followed by ring formation using TosMIC to deliver fludioxonil (2). Table 15.2.1 lists the chemical and physical properties of fenpiclonil (1) and fludioxonil (2). 

The most common crown ethers are shown in Fig. 22. Since application of lUPAC rules to polyethers leads to somewhat cumbersome designations, we will follow the simple crown nomenclature proposed by Pedersen Polyethers are built up from 1,4-dioxa units, O—CH —CH —O. The minimum energy conformation of these units is staggered with torsion angles about C-C bonds being synclinal (60°) and about C-O bonds being antiperiplanar ( 180 °C) (for definitions see Fig. 23). These preferences, however, do not preclude deviations if required by ring formation or cation complexation. 

Many important chains contain bonds that are locked into a single conformation due to restrictions imposed by ring formation, as in the benzene ring of poly (ethylene tereph-thalate), or electronic structures (as in the amide unit of nylon-6, which strongly prefers the planar trans conformation). These rigid units are often treated with virtual bonds, where a single virtual bond spans the rigid unit. Several instances where virtual bonds have been used are summarized in Table 3.5. 

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