Vinyl aniline

Rctrosynthetic path a corresponds to Pd-catalysed exo-trig cyclization of o-halo-JV-allylanilines. Path b involves the endo-trig cyclization of o-halo-JV-vinyl anilines. Path c is a structurally similar cyclization which can be effected photochemically in the absence of an o-substituent. Retrosynthetic path d involves intramolecular Friedel-Crafts oxyalkylation followed by aromatiz-ation. 

V-(Methoxyprop-2-yl) -8-methyl-2 oxo-1,2,3,4-tetrahyd ro-quinoline, see Metolachlor 7V-(Methoxyprop-2-yl)-yV-(2-methyl-6-vinyl) aniline, see Metolachlor... 

Some synthetically useful reactions not covered in the above sections should be mentioned. An unusual heterocyclization to form indole derivatives is found in the aminomercuration of allylenaminones (equation 130).261 Palladium(II)-catalyzed cyclizations of o-allyl- and -vinyl-anilines and amino-quinones are discussed elsewhere.30 Other electrophiles used to form dihydroindole derivatives include phenylselenenyl chloride216 and methyl(bismethylthio)sulfonium salts.231... 

All of these processes are of limited synthetic utility because of the requirement of the use of stoi chiometric amounts of palladium complexes. However, by judicious choice of reactants and condition the above-mentioned impediments to catalysis can be overcome. For example, an efficient palladium(II) catalyzed cyclization of o-allyl- and o-vinyl-anilines to indoles has been developed (equation 14).28 Be cause arylamines are -106 less basic than aliphatic amines, and because the cyclized product in thi system gave an enamine (indole) stabilized by aromatization, the problems of catalyst poisoning by sub strate or product were circumvented, and catalysis was successfully achieved. The system was quit tolerant of a variety of functional groups and was used to prepare indoloquinones in excellent yieli... 

In this manner, a hydroformylation/condensation sequence of 0-vinyl-anilines give indoles directly. The starting o-vinylanilines are obtained by Heck reaction of the corresponding o-haloanilines. Hydroformylation of these styrene-type olefins proceeds preferably at the benzyl carbon. Intramolecular condensation gives pharmacologically interesting tryptophols and tryptamines in mediocre to good yields (Scheme 12, Table 1) [47]. 

Reference spectra for these compounds involving anilines show differences between aniline anils and iV-vinyl anilines that are characterized by the difference in the spectra of 2,3,3-trimethylindolenine and l,3,3-trimethyl-2-methyleneindoline. No suitable carbinol-amine spectrum could be found, and the values given for this... 

O-Acetylation. Methyl o-aminophenylacetate refluxed 2 hrs. with dimethyl acetyl-enedicarboxylate in abs. benzene, evaporated, and chromatographed on silica gel, whereby the ca. 1 1 mixture of cis- and trans-isomers is completely converted to the trans-form 2-methoxycarbonylmethyl-N-[l,2-bis(methoxycarbonyl)vinyl]-aniline (Y 80%) added to a soln. of Na in methanol, and allowed to stand 15 hrs. at room temp. 3-hydroxy-2-methoxycarbonylmethyl-4-methoxycarbonylquino-... 

Three novel organic optical materials, 4 -(N,N-dihydroxyethylamino)-4-(pyridine-4-vinyl) stilbene, N- ((4- N, N-dihydroxyethylamino)benzylidene) -4- (pyridine-4-vinyl) aniline, and 4 -(N,N-dihydroxyethylamino)-4-(pyridine-4-vinyl)azobenzene, were synthesized [105]. Tolunitriles reacted vdth donor-substituted aromatic aldehydes in high yielding reactions of the synthesis of donor-acceptor cyanostilbenes without the need of inert atmosphere. The keys to this reaction were the use of anhydride DMF solvent and the phase transfer agent - tris(3,6-dioxaheptyl)amine (TDA). High yields of stilbenes were also obtained with amino-substituted aromatic aldehydes [106]. 

The Widman-Stoermer cinnoline synthesis refers to the conversion of an o-vinyl aniline 1 to the representative cinnoline 2 via an in situ generated diazonium intermiediate/ Cinnolines have shown utility as anticancer, fungicidal, bactericidal, antithrombotic, and antituberculosis agents as well as having been shown to embody anesthetizing and sedative activity. Widman and Stoermer s approach to cinnolines represents a classical approach to this ubiquitous core structure. 

The cinnoline ring system was first prepared by Richter via diazotization and subsequent cyclization of o-aminophenylpropionic acid. Subsequent efforts by Widman, and later Stoermer, demonstrated access to the cinnoline ring system via subjection of o-vinyl anilines to diazotization conditions. Other than the observation by Stoermer that o-aminocinnamic acid does not undergo cyclization when exposed to diazotization conditions, initially, little attention was paid to the influence of Ri and R2 on the cyclization of 1 to 2. Sixty years after Widman s first disclosure, Simpson and Schofield " began to address the role of Ri and R2 vide infra). There is a remarkable dearth of literature featuring the title reaction beyond the efforts of Simpson and Schofield, owing, in part, to many other useful methods to prepare cinnolines. 

Cumulative efforts of Stoermer, Simpson and Schofield have led to a fairly comprehensive understanding of the circumstances in which the Widman-Stoermer reaction might be expected to succeed. Initial efforts of Simpson and Schofield, " demonstrated that cinnoline formation is not expected to succeed for o-vinyl anilines (1) where Ri = H or CO2H and R2 = aryl, CO2H, CO2R, CN, 2-pyridyl, or 2-quinolyl. On the other hand, for compounds (1)... 

N-allyl/N-vinyl anilines were characterized by a rearrangement of the ahphatic moiety. The aromatic system had not been touched during the course of the process (Winterfeldt quinolone synthesis [15c]). The rearrangement of a NH allyl vinyl amine failed [15dj. 

When applied to olefinic anilines, this type of process leads to fused lactams. While o-vinyl anilines selectively yield indolones (Scheme 55), o-allyl anilines afford complex mixtures of five-, six-, and seven-membered rings. 

In contrast, Muniz reported an indole synthesis from 2-vinyl anilines 13, which relies on activation of the alkene moiety by the hypervalent iodine reagent [9]. The reaction employs a sterically congested Koser reagent generated in situ from iodosobenzene and the bulky sulfonic acid 15. The reaction provides synthetically unique access to 2,3-unsubstituted indoles 14 and can also be conducted under catalytic conditions. 

Benzylthio-3-cyanoquinolines bearing fluorine atom in position 4 have been obtained on heating of functionalized N-vinyl anilines 53 the latter are prepared by condensation of the corresponding a-fluorine-containing vinyl sulfides with anilines (Scheme 20) [31], Alkaline hydrolysis of the reaction products afforded the corresponding 3-cyanoquinolin-4-ones 54. 

Pd-catalyzed reactions tolerate a great variety of functional groups (5). Vinyl benzamide or vinyl anilin are examples obtained in good yields and at polymerization-grade purity. By substitution of ethylene with acrylic acid derivatives products with cinamic acid structures are obtained (d). 

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