Organic reactions in aqueous solution at room temperature. II. Influence of pH on condensations involving the linkage of carbon to carbon, of carbon to nitrogen, and of carbon to sulfur was written by Bethell, J. R.;Maitland, P.. And the article was included in Journal of the Chemical Society in 1961.Category: pyrazoles-derivatives This article mentions the following:
Further simple reactions under “physiological” (“cell-possible”) conditions were described, leading to the formation of the C6H6, the pyrazole, and the thiazole ring system. Two examples of the Michael reaction under mild conditions were given. The general exptl. conditions adopted were those described in the previous paper. The work was described in four sections. (a) Double C-C Claisen-Knoevenagel condensation of two C-3 aliphatic units to give a benzene derivative Diethyl 2-hydroxy-4,6-dimethylisophthalate (I) was prepared by condensing acetylacetone with diethyl acetonedicarboxylate. The reaction was carried out in a saturated buffered aqueous solution The results showed that I was formed in the pH range 5.6-9.2, the highest yield (86%) of pure product being precipitated at pH 7.3-7.6. This condensation could therefore proceed by the acid- or base-catalyzed mechanisms, and the fact that it took place within the physiol. pH range supported the possible origin of some natural benzene derivatives by a C-3 C-3 route of this type. (b) The Michael reaction (cyanoethylation). C-C condensation of Me acetoacetate (II) and vinyl cyanide (III) and C-N condensation of PhNH2 and III. The influence of pH on two examples of cyanoethylation was studied. (1) II and III. II (2.32 g.) in buffer solution with 2.12 g. III in 40 ml. buffer solution left 6 days at room temperature gave varying yields of diethyl 浼?浼?bis(2-cyanoethyl)acetoacetate (IV), m. 154-6鎺? The maximum yield of IV was 46% at pH 10.7 and fell to 9.7. There was no trace of the monocyanoethylated product. No product was obtained in acid solution, which showed that this Michael type reaction could only proceed by the base-catalyzed mechanism. (2) PhNH2 and III. III (1.06 g.) in 50 ml. buffer solution and 1.86 g. PhNH2 in 150 ml. buffer solution left 20 days at room temperature gave N-(2-cyanoethyl)aniline (V), m. 50-1鎺? at varying pH values. The results showed that pure V was precipitated over the pH range 5.1-11.6 with a maximum yield of 44-5% at pH 7.5-10, except around pH 9.2 where there was a repeatable but unaccountable decrease of 5-6%. Although the duration of the actual experiment was 20 days, equimolar amounts of PhNH2 and III in the buffer solution at pH 8.8 gave a 29% yield after 7 days; using double the amount of III under the same conditions gave 59% V. (c) C-N condensation to give a pyrazole derivative Semicarbazide-HCl (2.2 g.) and 2 g. acetylacetone in 70 cc. buffer solution gave 3,5-dimethylpyrazole-1-carboxamide (VI), m. 111-13鎺? under a variety of pH values. The results showed that the highest yield of VI, 86%, was precipitated at pH 4.1 and diminished to 17% at pH 8.2 and nil at pH 10. The duration of the experiments to obtain the maximum yield at each pH varied from 2 hrs. to 12 days. Below pH 4, hydrolysis and decarboxylation to 3,5-dimethylpyrazole was observed. (d) Combination of C-S and C-N condensations to give a thiazole derivative When buffer solutions of 0.625 g. N-ethylmaleimide and 0.38 g. CS(NH2)2 were left 2 days at room temperature, N-ethyl-浼?(2-imino-4-oxothiazolidin-5-yl)acetamide (VII) was obtained, m. 210-12鎺? The highest yield of VII, 74%, was obtained at pH 5.6. The rapid decline in the yield of VII on the alk. side was probably due to its hydrolysis. It was difficult to find a satisfactory mechanism for the formation of VII. It was formed, not only in aqueous alc., in aqueous buffers, but also in absolute alc. Two reactions would seem to be necessary: addition of the thiol form of thiourea across the double bond of the maleimide followed by nucleophilic attack by the more basic thiourea amino group on the adjacent carbonyl group, with subsequent proton shift. In the experiment, the researchers used many compounds, for example, 3,5-Dimethyl-1H-pyrazole-1-carboxamide (cas: 934-48-5Category: pyrazoles-derivatives).
3,5-Dimethyl-1H-pyrazole-1-carboxamide (cas: 934-48-5) belongs to pyrazole derivatives. Pyrazoles, a five-membered heterocycle containing two adjacent nitrogen atoms, are the core structures found in a number of molecules that possess a wide range of pharmaceutical and agricultural activities. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Category: pyrazoles-derivatives
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics