Guanidine Compounds. Ii. Preparation of Mono- And N,n-Di-Alkylguanidines

Abstract

1-Guanyl-3,5-diniethylpyrazolc nitrate is superior to S-methylisothiourorlium sulphate as a reagent for preparation of simple salts of mono-and N,N-di-allcylg~~anitlines from cyclohesylaniine, tra~zs-2-anii11ocyclo1~~~a11o1, pyrrolidine, and piperidir~e. S-h'Icthylisothiouro~~iurn sulphate, however, gave a higher conversion in the case of tlimctIi>.lan~ine. Cyanamide is not as useful a guanylatilig agent as those n i c~~t i o~i e d above. The paper cliromatography of the nio~io-and N,N-di-alkylguanidines and the parent arni~rcs \\,as studied using four solvent systems. l NTRODUCTIONOf the ilumerous methods reported in the literature for preparation of mono-and N,N-di-alliylguanidines, those \vhich have been used most frecluently are the Erlenmeyer synthesis ( I ) , from amine salts and cyanamide (2, 3 , 1 , 5 , G ) , and the Rath1.e synthesis ( 7 ) , from amines and an all;ylisothiouronium or alkylisouronium salt (8, 9,10,11,12). Both methods, however, frequently lead to poor jrields of all<ylguanidines, clue principally to the formation of dicyandiamide by dirnerization of CJ-anarnide on the one hand (13) T h e sole by-product was 3,5-dimethylpyrazole (11) and the method thus seemed a suitable candidate t o replace the older methods of synthesis, provided t h a t salts other than the picrates used (15) t o simplify recovery of the al1;ylguanidines proved i s o l d l e in high yields. Since we required a number of all<ylguanidines in connection with other studies, it seemed of interest t o evaluate the usefulrless of t h e three methods of synthesis. RESULTS AND DISCUSSIONSeveral procedures for guanylation of amine salts with cyanamide in aqueous or alcoholic solution (2,4,5,6) were examined b u t all of these in our hands gave yields of alkylguanidines in the range 0-20%. T h e only method found t o be effective was a fusion technique due t o Sugino et al. (16,17), by which procedure cyclohexylguanidine hydrochloride was obtained in 48% yield. Guanylation of trans-2-aminocyclohexanol '

The A Priori Design and Selection of Ionic Liquids as Solvents for Active Pharmaceutical Ingredients

“…[47] The new ILs we present in this work are based on singly substituted guanidinium cations,w hich leads them to possess differentp roperties to the highly substituted ILs described above.T ot he best of our knowledge, such monoalkyl guanidinium ILs have not been described in the IL literature although there are an umber of studies concerned with similar salts bearing different anionsi nthe biochemistry literature. [54][55][56][57][58] Monoalkylguanidinesa re strong Brønsted bases,l ike guanidine itself, [59] giving the corresponding guanidinium ions negligible Brønsted acidity and thus forming stable cations. As these are an ew class of IL cation, it was of interest to compare the solvent properties of these ILs with other commonly used cations.…”

Synthesis of short cationic antimicrobial peptidomimetics containing arginine analogues

“…The coupling reactions were performed using the HBTU/HOBt method to give the Boc‐protected peptidomimetics 1a–8a . After the removal of Boc‐protecting groups, the introduction of guanidine moiety in compound 1b to obtain 1 , was carried out using 3,4‐dimethyl‐1 H ‐pyrazole‐1‐carboximidamidenitrate salt as guanylation reagent . Unfortunately, the use of this strategy in the synthesis of the SAMPs derivatives 2–8 resulted disappointing, giving low yields and difficulties in the isolation and purification of the products.…”

A general synthesis of the acarnidines

“…Phascoline (32) and phascolosomine (33) were found in the viscera rather than the muscle tissue of three species of a marine worm. Phosphocreatine (34) is the phosphagen of vertebrates while phosphoarginine (35) …”