Demethylation of Cotinine in Vivo¹

Abstract

Aug. 5 , 1939 DEMETHYLATION OF COTININE in I.'ZVO 395 1 bath for 12 hr. The manganese dioxide was centrifuged off and the alkaline supernatant liquid extracted with ether. The aqueous layer was then evaporated to small bulk and acidified with a few drops of concentrated hydrochloric acid and extracted many times with ether (500 ml.). The dried ether extract was evaporated and the crystalline residue sublimed in v u 2 0 to yield phthalic anhydride (24.2 mg., 42%), m.p. 130 . N-Phenylphthalimide was obtained by refluxing a few mg. of the anhydride with a drop of aniline and several drops of acetic acid. CrystallizaDtion from ethanol gave fine colorless needles, map. 212 , not depressed on admixture with authentic material.Anthranilic Acid (XI).'*-The phthalic anhydride (15 mg.) was dissolved in concentrated sulfuric acid (0.2 ml.), cooled and sodium azide (30 mg.) added. The mixture was warmed at 110' on a metal-bath for 30 minutes and then allowed to cool overnight. Ice was then added and the solution brought to a p H of about 5 by the addition of SOdium hydroxide. Extraction of this solution with ether yielded anthranilic acid, purified by sublimation (10.2 mg., 73%), m.p. 145-146", not depressed on admixture with authentic material.

Formation of Nornicotine and Other Metabolites From Nicotine in Vitro and in Vivo

“…The same metabolite was demonstrated in dog urine following the administration of nornicotine (17) and of cotinine (18). A/IcKennis et al reported (5) that paper chromatograms of urine from rats given cotinine showed demethylcotinine while human urine obtained under sinlilar conditions showed no evidence of demethylcotinine.…”

Vapor pressure data of nicotine, anabasine and cotinine using differential scanning calorimetry

“…There is no reference data available for the vapor pressure range measured in the present study. Some indicative data of low vapor pressure values found in three different literature sources [35][36][37] are shown in Table 7. These literature values are boiling ranges, not boiling points of cotinine, and therefore, are not presented in Fig.…”

Cyclopropylamines from N,N‐Dialkylcarboxamides and Grignard Reagents in the Presence of Titanium Tetraisopropoxide or Methyltitanium Triisopropoxide

“…Among the variety of drugs that have an N,N-dialkylcarboxamide moiety, (S)-Cotinine 65, a metabolite of nicotine with antidepressive activity, was chosen. [26] The lactam 65 was treated with ethylmagnesium bromide (6 a) in the presence of methyltitanium triisopropoxide, and indeed, the spirocyclopropane derivative 66 could be isolated in 77 % yield (Equation (1) in Scheme 12). Thus, Cotinine can be regarded as a prime example for the one-step modification of a biologically active substance without influencing the stereochemical features.…”