Alkoxy substituents

Diels-Alder reactions of oxazoles afford useful syntheses of pyridines (Scheme 53) (74AHC( 17)99). A study of the effect of substituents on the Diels-Alder reactivity of oxazoles has indicated that rates decrease with the following substituents alkoxy > alkyl > acyl >> phenyl. The failure of 2- and 5-phenyl-substituted oxazoles to react with heterodienophiles is probably due to steric crowding. In certain cases, bicyclic adducts of type (359) have been isolated and even studied by an X-ray method (87BCJ432) they can also decompose to yield furans (Scheme 54). With benzyne, generated at 0°C from 1-aminobenzotriazole and lead tetraacetate under dilute conditions, oxazoles form cycloadducts (e.g. 360) in essentially quantitative yield (90JOC929). They can be handled at room temperature and are decomposed at elevated temperatures to isobenzofuran. 

Disilacyclobutanes can be functionalized by electrophilic or nucleophilic substitution at silicon, depending on the nature of the substituents. Alkoxy groups may be replaced by halogens in the presence of a Lewis acid, for example, by FeCl3 (Equation 16) <1997PSA3193, 2003JOM272>. 

The same is true for the following substituents alkoxy (-OR), esters (-OCOR), amines (-NH2, -NHR, -NIT,) and amides (-NHCOR). In all these cases, there is either a nitrogen or an oxygen next to the ring. Both these atoms are nucleophilic and have lone pairs of electrons which can be used to form an extra bond to the ring. The ease with which the group can do this depends on the nucleophilicity of the attached atom and how well it can cope with a positive charge. 

Adjacent atoms with one or more unshared pairs of electrons strongly stabilize a carbocation. Table 3.11 (p. 304) indicates the stabilization of the methyl cation by such substituents. Alkoxy and dialkylamino groups are important examples of this effect. 

Electronegative substituents (alkoxy groups, halogens) in the 2(6) position of the tetrahydropyran system prefer to adopt the axial position in the conformational equilibrium. 

This reactivity pattern underlies a group of important synthetic methods in which an a-substituent is displaced by a nucleophile by an elimination-addition mechanism. Even substituents which are normally poor leaving groups, such as alkoxy and dialkylamino, are readily displaced in the indole series. 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

Some of the most powerful activating substituents are those m which an oxygen atom IS attached directly to the nng These substituents include the hydroxyl group as well as alkoxy and acyloxy groups All are ortho para directors... 

In cationic polymerization the active species is the ion which is formed by the addition of a proton from the initiator system to a monomer. For vinyl monomers the type of substituents which promote this type of polymerization are those which are electron supplying, like alkyl, 1,1-dialkyl, aryl, and alkoxy. Isobutylene and a-methyl styrene are examples of monomers which have been polymerized via cationic intermediates. 

Chloromethylation of the aromatic nucleus occurs readily with alkyl and alkoxy substituents accelerating the reaction and halo, chloromethyl, carboxyl, and nitro groups retarding it. 

Properties. One of the characteristic properties of the polyphosphazene backbone is high chain dexibility which allows mobility of the chains even at quite low temperatures. Glass-transition temperatures down to —105° C are known with some alkoxy substituents. Symmetrically substituted alkoxy and aryloxy polymers often exhibit melting transitions if the substituents allow packing of the chains, but mixed-substituent polymers are amorphous. Thus the mixed substitution pattern is deUberately used for the synthesis of various phosphazene elastomers. On the other hand, as with many other flexible-chain polymers, glass-transition temperatures above 100°C can be obtained with bulky substituents on the phosphazene backbone. 

The alkyl and alkoxy substituents of phosphate or phosphonate esters also affect the phosphorylating abiUty of the compound through steric and inductive effects. A satisfactory correlation has been developed between the quantitative measure of these effects, Tafts s O, and anticholinesterase activity as well as toxicity (33). Thus long-chain and highly branched alkyl and alkoxy groups attached to phosphoms promote high stabiUty and low biological activity. 

Fig. 5. Synthesis of l-amino-4-hydroxyanthraquinones with alkoxy substituents in the 2-position. See Table 4.

Fig. 2. Improvement in 5 achieved by alkoxy substituents. = only carbon atoms H = with one oxygen atom. To convert MPa to (cal/cm ) , divide...

Substituted PPVs have been prepared using similar techniques. The earliest reports described methyl substituents (104,105), and more recentiy alkoxy substituents on the aromatic ring have been incorporated into the polymer stmctures (107—109). The advantage of long-chain alkoxy (butoxy or hexyloxy) substituents is that not only is the precursor polyelectrolyte soluble, but after conversion the substituted PPV is also soluble (110—112). 

---