Anomalous reactions

Anomalous Fischer cyclizations are observed with certain c-substituted aryl-hydrazones, especially 2-alkoxy derivatives[l]. The products which are formed can generally be accounted for by an intermediate which w ould be formed by (ip50-substitution during the sigmatropic rearrangement step. Nucleophiles from the reaction medium, e.g. Cl or the solvent, are introduced at the 5-and/or 6-position of the indole ring. Even carbon nucleophiles, e.g. ethyl acetoacelate, can be incorporated if added to the reaction solution[2]. The use of 2-tosyloxy or 2-trifluoromethanesulfonyloxy derivatives has been found to avoid this complication and has proved useful in the preparation of 7-oxygen-ated indoles[3]. 

Similarly, the A-mesitylbydrazone of acetophenone gives 2-phcnyl-4,5,7-trimethylindole as a minor product (10%)[5]. 2,4,6-Trialkylphenylhydrazones have also been observed to give 5,6,7-trialkylindoles as the result of a formal 3a 6 shift[6]. These reactions probably occur via a 1,5-shift followed by a 1,2-shift. 

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Murakami, H. Takahashi, Y. Nakazawa, M. Koshimizu, T. Watanabe and Y. Yokoyama Tetrahedron Lett. 30, 2099 (1989). 

Murakami, T. Walanabe, Y. Yokoyama, J. Naomachi, H. Iwase, N. Watanabe, M. Morihata, N. Okuyama, H. Kamakura, T. Takahashi, H. Atoda, T. Tojo, K. Morita and H. Ishii, CItern. Pharm. Bull. 41, 1910 (1993). 

When the reaction of enaminone (223) and dimethyl methoxymethy-lenemalonate was carried out in THF in the presence of butyllithium, pyrrolidinomethylenemalonate (224) was obtained in 4% yield. When this reaction conducted in DMF in the presence of potassium tert-butylate, pyrrolidinomethylenemalonate (224) and 2,3-dihydro- l//-indolizin-5-one (225) were prepared in 21 and 46% yields, respectively (88AP345). 

Instead of the amino group, position 4 of the imidazole ring was involved in the reaction of 5-amino-2-mercapto-1 -methylimidazole (226) and EMME when they were heated under nitrogen, giving 4-imidazolylmethylenemalo-nate (227) (78H241). The same product was obtained when the hydrochloride of imidazole (226) was reacted with N,N-dimethylaminomethylene-malonate in DMF or acetic acid. 

The reaction of 6-amino-l,3-dimethylpyrimidine-2,4-dione and EMME in the melt at 210°C gave 7-oxopyrido[2,3-c/]pyrimidine (228) in 29% yield (76JOC1095), whereas in boiling acetic acid overnight, the yield was 85% (85JHC1469). 

When the reaction was conducted under basic conditions, in boiling ethanol overnight in the presence of sodium ethoxide, diethyl 4-pyrimidi-nylaminomethylenemalonate (229) was obtained in 99% yield. Compound 229 could by cyclized to the isomeric 5-oxopyrido[2,3- /]pyrimidine (230) in 89% yield on boiling in diphenyl ether for I hr (85JHCI469). 

The reaction of 4,6-diamino-2-methylthiopyrimidine and EMME in boiling acetic acid overnight gave 7-oxopyridof2,3- /]pyrimidine (231) in 36% yield (85JHC1735), whereas in boiling ethanol overnight, this reaction afforded yV-(6-aminopyrimidin-4-yl)aminomethylenemalonate (232) in 85% 

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In view of the known behaviour of pyrazines during nucleophilic substitution reactions, it comes as no surprise that anomalous reactions appear during nucleophilic substitution... 

Variations in the reaction temperature and in the proportions of the ketone and PCI5 were appreciably reflected in the ratio of the amounts of compound 9 obtained in the first stage to the total content of 7 and 8 and then proportionally in the composition of the final products. In the interaction of the ketones with PCI5, an excess of the latter and high temperature make the anomalous reactions more significant. 4-(l,2-Dichlorovinyl)-3,5-dimethyl-l//-pyrazole (9) was obtained individually by the action of more than a twofold excess of PCI5 on the acetylpyrazole 6 at 80°C in 50% yield. Under the influence of NaNHa in liquid NH3, dichloroethy-lene 9 was converted into chloroacetylene 10 by loss of a molecule of HCl (yield 77%) (Scheme 28). 

A similar phenomenon was observed for 3-amino- and5-amino-4-iodopyrazoles. The anomalous reaction in which the products of oxidative coupling of terminal acetylenes (up to 90%) are present along with the products of deiodination (up to 90%) has been described for the first time [99JCS(P1 )3713] and will be considered below in the part related to cross-coupling of 4-iodopyrazoles. 

The higher concentration of a chemical in the environment, the more children with anomalous reactions could be found. Children living in polluted areas had hypertrophy of tonsils, enlarged lymphatic nodes, and enlarged livers (Tabl. 2). 

An anomalous reaction of the hydroxy-activated ester, ethyl lactate hcis also been noted )2). With p-phenethylbiguanide this gave, in addition to the expected guanamine (XCII), the corresponding hydroxy-compound (XCIII), but no chemical evidence for this formulation was given. 

Group IVA Donor Ligands. The anomalous reactions of PhaSiCl with metal carbonyl anions are discussed on p. 180. Only in the case of [Co(CO)3PPh3] was the normal substitution product obtained. GeH3Br reacts with Na-[Co(CO)4] in ether to produce [H3GeCo(CO)4]. The trideuterio-compound has also been prepared and spectroscopic properties reported for both compounds. The preparation and attempted preparation of halogen-bridged Ge-M compounds is referred to on pp. 180 and 200. In the case of cobalt. 

Anomalous reactions are reported for some butenolides. Thus compound 46 does not cyclize in the expected manner [130]. Formation of the observed products can be rationalised on the assumption that electrogenerated base can interact with... 

The Diels Alder reaction of the acyclic diene and 146 may result in unexpected products, however. As reported by Ried, the reaction of 1,4-diphenylbutadiene and 146 may, under drastic conditions, give the aromatized compound (148) and l,3,4,7-tetraphenylbenzo[c]furan (149) in varying amounts, depending on the conditions. In methylglycol/propanol (6 hr reflux) a substance was isolated (mp 147-148°C, 59%) which has tentatively been formulated as 150. One final goal of the sequence described seems to be unaffected by these anomalous reactions, however Diels-Alder adducts of benzo[c]furans can be obtained in a one-step reaction from a diene, 146, and an appropriate olefinic compound in acetic acid/acetic anhydride as shown in Eq. (7). ° ... 

Some anomalous reactions looking like forbidden [2+2] pericyclic cycloadditions. 

With the pattern for [2+2] cycloadditions fresh in mind, we turn to the anomalous reactions that appear to be forbidden [2+2] cycloadditions taking place thermally under mild conditions. 

One group of anomalous reactions is that of ketenes with alkenes. These reactions appear to have some of the characteristics of pericyclic cycloadditions, such as being stereospecifically syn with respect to the double... 

An anomalous reaction of 2-benzenesulfonyl-3-aryloxaziridines (Davis reagents) with indoles has been reported.48 hi this it appears that a re-bond in the indole acts nucleophilically to attack the O of the oxaziridine ring and thereby cleave the O—N bond. 

Attempts to carry out what are apparently trivial reactions can often lead to completely unexpected results. There are many causes of such anomalous reactions, but perhaps the most common is an injudicious choice of reaction conditions, as illustrated by the following example. 

J. O. Deferrari, R. M. Lederkremer, B. Matsuhiro, and M. I. Litter, Anomalous reaction of D-gluconamide with benzoyl chloride in anhydrous pyridine, Carbohydr. Res., 14 (1970) 103-107. 

Certain exceptions to this general scheme have been noted in which the normal hydrogenation of the nitrile group has not taken place. In these cases, a hydrolytic reaction has occurred, with the formation of an aldonic acid instead of the expected aldose.12 The anomalous reaction occurs when the nitrile exists in the (isomeric) iminolactone form for example, compound I is hydrolyzed directly, before hydrogenation can take place. This isomerism of the aldononitriles was established by Papadakis and Cohen,16 and the cyclic structure I was postulated by Wolfrom and coworkers.108... 

The reaction of azirines with Grignard reagents is an anomalous reaction of imines. Normally an a-hydrogen is abstracted to give the enamine anion which is unreactive toward further attack of the Grignard reagent.64 The enamine derived from a 1-azirine is a 2-azirine (146) it is an unknown and probably unstable compound (Section I,A). 

Lutz and Welstead55 described an anomalous reaction. If tetra-phenylfuran is treated with bromine in ethanol-ether, the expected addition product (46) is obtained. However, if ether alone is used, the dibenzoylethylene derivative (45) forms. Finally, if tetraphenylfuran in ether is treated with an excess of bromine, the authors found that 47 was produced, nuclear bromination having taken place ... 

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