Aniline derivatives formylation

There are a few alkoxy " or trimethylsilyloxy butadienes which react with the Vilsmeier reagent to give formylated products in moderate yields (Eqs. 49 and 50). In the latter case the products are isolated as aniline derivatives 57. 

In connection with an investigation of the fluorescent characteristics of derivatives of 2,2 -bithienyls, a number of heterocyclic substituted thiophen derivatives, such as (199)—(204) and their formyl derivatives, have been prepared. The quinoline derivatives were obtained from the appropriate 2-lithiobithienyl and quinoline, whereas the benzimidazolyl, benzoxazolyl, and benzothiazolyl derivatives were prepared by the condensation of a cyanothiophen or 5-cyano-2,2 -bithienyl with the appropriate aniline derivative. (204) was prepared through a Fischer indole synthesis. ... 

Hydroformylation of substrates incorporating O- or N-nudeophilic moieties leads to cyclic hemiacetals, acetals, 0,N-acetals, or enamines depending on the reaction conditions and the functional groups of the substrates. In the total synthesis of the anticancer agent, natural product leucascandroUde A (24), three different carbonyla-tion steps were incorporated (Scheme 12.1). Alkene 20 underwent a cyclohydrocar-bonylation reaction under hydroformylation conditions, resulting in the formation of hemiacetal 21. The other two carbonylation steps involved formylation of 18 and intramolecular alkoxycarbonylation of alkene 22 [28]. Various tryptamine derivatives [29] and the framework of piperidine alkaloids [30] were also synthesized via cyclohydrocarbonylation starting from functionalized homoallylic amines or aniline derivatives, respectively. 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

An important class of cationic dyes, particularly for yellow to bluish-red hues, is derived from Fischer s base by condensation with 4-formyl-substituted anilines, or from Fischer s aldehyde (which may be prepared from Fischer s base via Vilsmeier formylation (B-71MI11205)) and an aromatic amine (Scheme 3). There are many examples of resonating charge dyes of this type which include a variety of aromatic amines and aldehydes. Of heterocyclic interest are the dyes formed by condensation of Fischer s aldehyde with... 

However, the analogous preparation of the parent 2-phenylbenzo[6]-furan (217) was not reported until cyclization of SchifFs base 216, derived from l-formyl-2-benzyloxybenzene and aniline, in the sense of... 

The unique transformation of formamides to ureas was reported by Watanabe and coworkers [85]. In place of carbon monoxide, formamide derivatives are used as a carbonyl source. The reaction of formanilide with aniline was conducted in the presence of a catalytic amount of RuCl2(PPh3)3 in refluxing mesitylene, leading to N,AT-diphenylurea in 92% yield (Eq. 56) [85]. They proposed that the catalysis starts with the oxidative addition of the formyl C-H bond to the active ruthenium center. In the case of the reaction of formamide, HCONH2, with amines, two molecules of the amine react with the amide to afford the symmetrically substituted ureas in good yields. This reaction evolves one molecule of NH3 and one molecule of H2. 

Anilino - 5a,8a - dihydro -1,3,7 - trimethyl - H- pyrrolo[3,4 - ( ]quinazoline- 2,4,6, (3H,5H,7H, 9Ef)-tetrones (94) were obtained in good yield by the sequential treatment of 5-formyl-1,3,6-trimethyluracil with (i) aniline to form the 6-methylene-5-(phenylamino)methylene derivative, via a [l,5]-hydrogen shift in the aldimine, and (ii) maleimide to achieve the central ring-forming cycloaddition reaction (Equation (53)) <90BCJ2938>. 

With the very active W-6 or W-7 Raney Ni (alkaline), desulfurization occurs before ring fission and /V-mclhylanilinc is the only product, while with less active W-5 and degassed W-7 Raney Ni in the presence of alkali, ring fission takes place to some extent before desulfurization, which may lead to o-aminothiophenol (isolated in its oxidized form, 2,2 -diaminodiphenyl disulfide) and aniline, probably via the formyl derivative as the intermediate as shown in Scheme 13.13.148... 

Aminomethylene derivatives of ketones and 1,3-dicarbonyls are used in order to incorporate a formyl group into CH-acidic heterocycles via initial reaction with ethyl orthoformate and aniline followed by hydrolytic cleavage, as is shown e.g. with barbituric acid301 (equation 224). 

Substituted purines may arise in mixtures with 9-substituted derivatives from direct alkylation of purine anions. They are best prepared however by Traube syntheses. Thus formylation of 4,5-diamino-6-benzylthiopyrimidine and ethylation of the formyl derivatives gave a formamidopyrimidine which readily cyclized to 6-benzylthio-7-ethylpurine in the presence of potassium carbonate (B-68MI40901, p. 31). The derivative is clearly a ready source of 7-substituted adenines by reaction with ammonia or amines, or of 7-substituted purines by dethiation with Raney nickel. 7-Methylguanine has also been obtained from 7-methyl-guanosine, sodium borohydride and aniline at pH 4.5 (B-78MI40903, p. 615). 

Starting with formyl derivatives of any aniline, the only species for which there is enthalpy of formation data is p-A,iV-dimethylaminobenzaldehyde, —137 1 kJmol-1, for the solid from Reference 39b as well as our archive. Likewise, for acetyl derivatives, the data are sparse. They are seemingly limited to the m- and p-acetylanilines, more commonly known as the isomeric 3- and 4-aminoacetophenones. For the former, there is the sole archival value of —173.3 0.5 kJmol-1 for the solid and —161.2 0.7 kJmol-1... 

Usefully functionalised quinolines are easily accessible from anilines the iV-acetyl derivative is simply reacted with the Vilsmeier reagent and a 2-chloro-3-formyl-quinoline results. One may speculate that a... 

When the stability and relatively low volatility of the components permit, the long reaction time can, of course, be shortened by working at higher temperatures. The TV-formyl derivatives of aniline, 2-naphthylamine, a>methyl-benzylamine, and menthylamine were prepared almost quantitatively by heating the base with ethyl formate for 1 hour at 100-110°.771... 

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