Reactions of the Side-chain

Further bisalkynylphosphine oxide (53) cyclizations have been applied to heterocyclic synthesis.45 The phosphine oxide (54) has been prepared as shown, and found to undergo Diels-Alder addition by an intramolecular pathway, to give (55).48 

Aromatic substituent effects due to phosphorus groups have been studied for a number of reactions.47 Thus ester hydrolysis and fluoride-displacement rates, for (56) and (57) respectively, are enhanced by phosphorus substituents (X = O or ), while the rate of hydrolysis of the halide (58) is enhanced for X = , but slowed for X = O.47 A perturbation M.O. analysis of these observations has been presented.48 

Nitration of various phenyl-49 and benzyl-phosphine60 oxides (59) has been described, and the P=0 group found to be mem-directing49 in the former case. Pyrolysis of the acyl azide (60)51 takes the course shown. 

A new synthesis of vinylphosphine oxides is available from the addition of secondary phosphine oxides to enol acetates to give (43), followed by thermolytic 

The a-halogenation of tertiary phosphine oxides has been investigated. Direct bromination of dibenzylphenylphosphine oxide gave all three possible diastereo-meric a,a -dibromo-derivatives (47). Alternative halogenation, via formation of the mono- or di-lithiated species followed by reaction with carbon tetrachloride, gave monochlorination products (48) with kinetically controlled diastereomeric ratios. 

2-Hydroxyalkylphosphine oxides, generated in various ways, have been used 

Unlike the analogous phosphonates, dialkoxymethyldiphenylphosphine oxides (66), readily obtained from chlorodiphenylphosphine and orthoformates, undergo the Horner-Wittig reaction with aldehydes and ketones and so offer a 

Various Reactions of the Side-chain.—4,5,6,7-Tetrahydrobenzo[6]thien-4-yl-urea was oxidized to the 7-oxo-derivative by ceric ammonium nitrate the 

Asakawa, E. Imamiya, and Y. Hamuro, Chem. Pharm. Bull., 1979, 27, 1468. 

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The reactions of benzyl chloride, benzal chloride, and ben zotricbl oride may be divided into two classes (/) reactions of the side chain containing the halogen and (2) reactions of the aromatic ring. 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

Thus, Diels-Alder condensation of 9 with methyl vinyl ketone affords the bicyclic adduct 24. The new ring is formed by approach of the dienophile from the face containing the nitrogen bridge, since this is in fact the least hindered side of the molecule (9a). Reaction of the side Chain ketone with propylmagnesium bromide then leads to intermediate 25 demethylation of the... 

The reactions of azofurazans have been used to obtain the hydrazine and the amino derivatives. For example, reactions of azofurazans, including macrocyclic azofurazan 196, with BunLi and the lithium derivatives of methylfur-azans were studied. Several competitive processes were found to occur (1) the addition of a Li reagent at the N=N bond (2) the redox reaction giving rise to hydrazofurazans and (3) the reaction of the side chain of azofurazan (Scheme 44) <2004RCB615>. 

This enzyme [EC 2.3.2.13], also known as protein glutamine y-glutamyltransferase, catalyzes the calcium ion-dependent reaction of the side chain of a glutamyl residue in a protein with an alkylamine to generate an A -alkylglutaminyl residue in the protein and ammonia. 

Figure 8-10 shows another pair of reactions for the halogenation of an aromatic compound. The reaction of the side chain is a free-radical substitution. Figure 8-11 shows the mechanism of this free-radical substitution. 

Reaction of the side chain hydroxyacetone in flumethasone (27-4) with periodic acid leads to cleavage of that function to give carboxylic acid (29-1) with the loss of the carbon atom at C-21. Further reaction of the very hindered acid group requires prior activation. Thus, acylation with diphenyl chlorophosphate leads to the mixed anhydride (29-2) this is not isolated, but treated immediately with methyl mercaptan. The product, tibecasone (29-3), is a quite effective topical anti-inflammatory agent [24]. Cleavage of the ester side chain would lead back to the inactive starting acid (29-1). 

Degradation. Penicillins are rapidly hydrolyzed by aqueous alkali to die corresponding penicilloic acids which arc stable as salts, but which decarboxylale on acidification to yield penilloic acids, Penicillins are also degraded by aqueous acids via initial reaction of the side-chain carbonyl group with the /i-lactam. 

The other major mechanism of pol3mier thermal degradation is by side chain (or substituent) reaction, shown in Figure 15.2. These reactions can either cause the elimination of the side chain or the substituent or cydization with the main chain. Upon elimination, volatiles are formed and the new polymer can react further by (1) main chain scission producing more volatiles or by (2) main chain cross-linking, which leads to cydization, unsaturation, graphitization, and finally carbon formation. A reaction of the side chain with the main chain causes cydization, which leads to graphitization and finally carbon formation. 

Cyclization is another frequent reaction of the side chain a typical example is the heat-resistant cyclized structures formed in heated polyacrylonitrile... 

Reactions of the Side-chain of Benzothiophens.—The C n.m.r. chemical shifts in 2-benzo[ j]thenyl carbenium ions have been investigated.The thermal decomposition of 2-azidophenyl 2-(3-methylbenzo[ >]thienyl) sulphide and of 2-azidophenyl 3-(2-methylbenzo[ ]thienyl) sulphide proceeded efficiently through spiro-benzothiazolines to give (161) and (162). 5-Hydroxy-3-methyl-benzo[ ]thiophen-2-carboxylic acid is most conveniently decarboxylated by refluxing with 48% hydrobromic acid. The decomposition of benzo[/)]thiophen-2(3//)-one and of 3-diazobenzo[/ ]thiophen-2-one at high temperatures provided convenient syntheses of benzothiet and the transient benzothiet keten. The decomposition reactions were carried out in the reactor of a photoelectron spectrometer.Heterotriptycenes have been obtained from... 

The wool fiber consists predominantly of proteins therefore, the reactions of wool are the reactions of the protein backbone (e.g., peptide bond hydrolysis) and the reactions of the side-chains of the 21 different types of amino acid residues of which wool is composed. Six of these amino acids (glycine, alanine, valine, leucine, isoleucine, and proline) are essentially chemically inert so are not normally available for chemical reaction. The reactions of the... 

Two other nonessential amino acids, asparagine and glutamine, are formed from aspartate and glutamate by reaction of the side-chain carboxylate groups with ammonium ions ... 

The substitution reactions of aromatic rings and the reactions of the side chains of alkyl-and alkenylbenzenes, when taken together, offer us a powerful set of reactions for organic synthesis. By using these reactions skillfully, we shall be able to synthesize a large number of benzene derivatives. 

Other more or less specific but less important reagents are for unsaturated compoimds molybdoarsenate [111], tetranitromethane [111, 113], osmium tetroxide [111, 113), p-anfinodimethylaniline-SOg [111, 113] for phenols, the nitroso reaction (Boute reagent) and Feigl reagent [113] for o-diphenols, phloroglucinol and vanadic acid [113] for reactions of the side chain, the Porter-Silber reaction [111], methyl ketones and formaldehydogens [111] and further modified reactions usual in PC [129]. 

Case (D) was observed in the intramolecular photo-Fries reaction of the side chain ester group in pciyfphaiyl acrylate)... 

A series of 1-aryl alkanols were investigated using polyoxometalates such as Wio032" as a photocatalyst (Scheme 6.4). A clean oxidation reaction of the side chain of the aryl alkanol led to the formation of the aryl ketone. This process supports a hydrogen transfer mechanism as the rate determining step. The efii-ciency of the reaction was mainly determined in the presence of oxygen [27]. 

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