Isoureas guanidines

Some examples of botanical origin will now be mentioned. Ergometrine powerfully stimulates the smooth muscle of the uterus, and constricts the muscular fibres of blood-vessels. Papaverine, a poppy alkaloid, has a direct anti-spasmodic action on gut muscle. A number of simple aliphatic amidines, guanidines, isoureas, and isothioureas, all of which are strong bases, raise blood-pressure and contract the intestine by direct action (Pastier, 1949). 

A -Chloro derivatives of amidines, isoureas and guanidines react with potassium 5-methyl-cyanodithioiminocarbonate (266) to yield 2,5-substituted 3-amino-1,2,4-thiadiazoles (Equation (37))... 

This section is new and only one article appeared in this area. The reaction of iV-/-butyl-iV -pyridazin-3-ylcarbodi-imide with amines, thiols, and alcohols was studied by Rakowitz and co-workers and yielded respectively novel guanidines, isothioureas, and isoureas <2002JHC695>. 

V-Chloro derivatives of amidines, isoureas and guanidines react with potassium 5-methyl cyanodithioiminocarbonate (320 R = Me) to yield thiadiazole systems of type (324 Scheme 114) (75BCJ310 73CL917). A related transformation occurs when the cyanothioiminocarbon-ates (322) and chloramine are allowed to condense at low temperature (76EGP119791). In this manner a variety of 5-substituted 3-amino-l,2,4-thiadiazoles (325) are obtained in good yields (Scheme 115). The use of ethoxycarbonylthioiminocarbonates (326) in this... 

Thiadiazole S.S -dioxides (336) have been prepared by the cyclization of N-halomethylsulfonyl-amidines and -guanidines (335 Scheme 120) <70JCS(C)1429>. N-chloromethylsulfonyl-isoureas and -isothioureas (337) cyclize in the presence of base and chloroformate esters to yield the related S,S-dioxides (92) which easily undergo chlorinolysis to produce (93 Scheme 121) (see also Scheme 45) (74BSF1580). 

Preparing to install the A and B rings, 34 was converted to isourea 35, remarkably without erosion of the C7 stereochemistry. The missing part was introduced with Grignard compound 36, and after oxidation and O-deprotection the two final rings were closed via guanidine formation with buffered ammonia (20 % overall) to yield penta-cycle 37. 

In contrast to guanidine-2-carbonitriles,395 isourea-3-carbonitriles (Ai-cyanocarbamimidates) and related compounds give good yields of chloro-l,3,5-triazines 11 in condensation reactions with (chloromethylene)iminium salts.397... 

The reactions are often carried out in an alcohol at room temperature, and the amidine is generally liberated from its hydrochloride by treatment with one equivalent of a base. Reaction times are short and the yields are high. It is also possible to employ isoureas, isothioureas and guanidines as the amidine component. The unstable 2-phenylisoureas (R3 = OPh) are prepared in situ. 

Cyclocondensation of substituted isothiocyanates 24 with amidines, isoureas, isothioureas or guanidines provides 1,3,5-triazine-2(1 //j-thiones 25 in good yield.433 43s Generally, aroyl isothiocyanates and imidoyl isothiocyanates are employed. 

Similarly, ethoxycarbonyl isothiocyanate (26) reacts with amidines, isoureas, isothioureas and guanidines to yield the corresponding tautomeric 4-thioxo-3,4-dihydro-l,3,5-triazin-2(l//)-ones 27.434... 

Guanidines from amines and isoureas Protection of a-amino acid groups... 

A methanolic soln. of O-methylisourea added to an aq. soln. of orni-thine-Cu-nitrate, prepared from ornithine nitrate and CuCOs, allowed to stand at room temp, for 2 days, acidified with H2S04. Cu removed with H2S, and isolated as flavianate —arginine flavianate. Y 94.5%. (F. Turba and K. Schuster, H. 283, 27 (1948) guanidines from isoureas s. a. V. M. Rodionov and 0. S. Urbanskaya, >K. 18, 2028... 

Tf20 reacts with dimethylcyanamide to afford an OJV-ditriflyUsourea. Reaction of this isourea with alcohols, thiols, or amines affords isoureas, thioisoureas, or guanidines, respectively (eq 87).134... 

Sulfenyl-amidines and iminoesters s. 13, 350 also sulfenyl-isoureas, -isothioureas, and -guanidines s. B. 92, 2563 (1959)... 

More recently, organotin azides and tin derivatives of hydrazine, 1,3-diphenyltriazene, formamide, urea, isourea, guanidine, amidine, carbo-diimide, carbamic, and thiocarbamic acids, an imidoether and imido-phosphoranes have been prepared, so that now almost every imaginable type of organotin-nitrogen compound has become known. 

Microwave-assisted reaction of 1-benzoyl-3-benzylthiourea and benzoyl-ethyl-thiocarbamate with benzylamine in dry media conditions using KF-Al Oj provides 1-benzoyl-3-benzylguanidine and 1-benzoyl-3-benzyl-O-ethylisourea in good yields (68 and 76%, respectively) (Marquez et al., 2006). Strong nucleophilic ben-zylamines promoted the elimination of sulfur as H S by attack on the thiocarbonyl group in both thiourea and thiocarbamates to afford guanidines and isourea, respectively. Very important nonpurely thermal MW specific effects were found responsible for stabilization by coulombic interactions between materials and waves. 

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