Cyanamide alkylation

Condensation of 2-phenyl-4-amino-5-benzoylthiazole with cyanamide yields the pyrimidothiazole (Scheme 88) (133) (49) 2-imino-3-aryl-4-amino-5-carbethoxy-4-thiazolines condense similarly with alkyl isothiocyanates (276). 

The synthesis of these disubstituied thioureas takes place in three steps. First the alkyl bromide is prepared by the action of hydrobromic acid on the corresponding alcohol (518). Then the dialkylcyanamide is obtained by treatment at 25°C with calcium cyanamide. The yields are of the order of 30 to 60%. Thioureas are obtained in a third step from the cyanamide by reaction at 40 C with HjS in the presence of pyridine. Yields ranged from 57 to 90% (518),... 

The nitrogen of aHphatic and aromatic amines is alkylated rapidly by alkyl sulfates yielding the usual mixtures. Most tertiary amines and nitrogen heterocycles are converted to quaternary ammonium salts, unless the nitrogen is of very low basicity, eg, ia tn phenylamine. The position of dimethyl sulfate-produced methylation of several heterocycles with more than one heteroatom has been examined (22). Acyl cyanamides can be methylated (23). Metal cyanates are converted to methyl isocyanate or ethyl isocyanate ia high yields by heating the mixtures (24,25). 

Although in the dry state carbon tetrachloride may be stored indefinitely in contact with some metal surfaces, its decomposition upon contact with water or on heating in air makes it desirable, if not always necessary, to add a smaH quantity of stabHizer to the commercial product. A number of compounds have been claimed to be effective stabHizers for carbon tetrachloride, eg, alkyl cyanamides such as diethyl cyanamide (39), 0.34—1% diphenylamine (40), ethyl acetate to protect copper (41), up to 1% ethyl cyanide (42), fatty acid derivatives to protect aluminum (43), hexamethylenetetramine (44), resins and amines (45), thiocarbamide (46), and a ureide, ie, guanidine (47). 

Substitutions. The cyanamide anion is strongly nucleophilic and reacts with most alkylating or acylating reagents (4) addition to a variety of unsaturated systems occurs readily (4). In some cases, a cyanamide salt is used in others, base catalysis suffices. Ethyl iodide reacts with sodium hydrogen cyanamide [17292-62-5] to form a trisubstituted isomelamine. 

Alkylation with a vatiety of common alkyl halides oi sulfates gives stable dialkylcyanamides. However, the intermediate monoalkylated compounds usually cannot be isolated and cychc trimers or cotrimers with cyanamide ate obtained (13). The reaction can be carried out efficientiy in water or alcohol. Allyl chloride is an especially useful reagent, producing diallylcyanamide [538-08-9J (4). 

An analogous decomposition of 5-amino-l,2,3,4-thiatriazole or 5-alkylamino-1,2,3,4-thiatriazoles gives cyanamide or an alkyl-cyanamide. ... 

Treatment of 3-amino-4-oxoquinazolines (9) with cyanamide gave the 2-amino-l,2,4-triazolo [l,5-c]quinazolines 11 as a result of cyclodehydration of the intermediate 3-guanidino-4-oxoquinazolines 10 (68CB2106) (Scheme 9). Similarly, reaction of the 3-amino-4-thioxoquinazoline 12 with alkyl or aryl isothiocyanates yielded the mesoionic l,2,4-triazolo[l,5-cjquinazolines 14 (84S881) (Scheme 10). 

A convenient way of obtaining secondary amines without contamination by primary or tertiary amines involves treatment of alkyl halides with the sodium or calcium salt of cyanamide NH2—CN to give disubstituted cyanamides, which are then hydrolyzed and decarboxylated to secondary amines. Good yields are obtained when the reaction is carried out under phase-transfer conditions. The R group may be primary, secondary, allylic, or benzylic. 1, co-Dihalides give cyclic secondary amines. 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

The sulphosuccinamate surfactants were first synthesized by American Cyanamid Company (currently Cytec, USA) in the late 1940s. Later in 1968, the alkyl sulphosuccinamate [10] was patented as a flotation collector. 

An efficient synthesis of 2-amino derivatives 256 is depicted in Scheme 70 2-halopyridines are first Ar-alkylated with various halides under microwave activation and next reacted with cyanamide under basic conditions <1999T2317>. A rapid parallel synthesis of derivatives bearing a benzoyl substituent at C-3 based on this reaction has been described <2002SL1544>. 

The addition of sodium azide to nitriles to give IH-tetrazoles is shown to proceed readily in water with zinc salts as catalysts. The scope of the reaction is quite broad a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. 

Imidates such as (115) react with cyanamide to give A -cyanoamidines (116), while the hydrochloride (117) is transformed to (118). Both (116) and (118) give 3-amino-1,2,4-oxadiazoles on treatment with hydroxylamine (Scheme 50) <81JHC37, 86JMC1540,92JMC369l>. However, other alkyl-idene cyanamides form either mixtures of 3- and 5-amino-1,2,4-oxadiazoles <87JHC275> or exclusively the 5-amino compounds (Equations (25), (26)) <94BCJ307>. 

Alkyl or aryl aminothiatriazoles (330) in contrast react with cyanates even at — 70°C to give 5-amidino substituted 1,2,4-thiadiazoles (331) weaker electrophiles, such as isothiocyanates, thiocyanates, and cyanamide do not react with aminothiatriazoles <85JOCl295>. 

Monodeprotonated form ofcyanoguanidine, at trr3f)s- Re(CNMe)(dppe)2 +. Hydrogen-cyanamide, at trons- Re(CNR)(dppe)2 (R = alkyl). 

Die Aminolyse von N-Alkyl- oder N-Aryl-dithiocarbamidsaure-methylestern mit a-Aminosau-ren fuhrt zu 4-Oxo-2-thiono-imidazolidinen (4-Hydroxy-2-mercapto-imidazolen Bd. E4, S. 501) und durch Umsetzung von a-Chlor-carbonsaure-amiden mit Cyanamid gelingt die Synthese von 2-Tmino-4-oxo-imidazolidinen (2-Amino-4-hydroxy-imidazolen Bd. E4, S. 979). 

Mit dem Dinatriumsalz von Cyanamid wird 3-Amino-1,2,4-benzotriazin-l,4-bis-oxid (81 %)320 gebildet, mit Cyan-acetamid hingegen 2-Aminocarbony -l-hydroxy-benzimidazol-3-oxid (78%)321 [analog reagieren 1-Nitro-alkane322-324 und (3-Oxo-alkyl)-sulfone]325 ... 

Die Kondensation von Nitroso-arenen und -alkanen mit Cyanamid liefert die entspre-chenden 1-Alkyl- oder l-Aryl-2-cyan-diazen-l-oxide1. Die Reaktion verlauft in Anwesen-heit von Diacetoxy-phenyl-jodoran, einem Reagenz, das Cyanamid in Cyan-nitren iiber-fuhrt und auf das N-Atom der Nitroso-Verbindung ubertragt ... 

The preparation of a pair of iminohydantoins invokes the addition of amide nitrogen to a cyano group for formation of the imidazole ring. The products exhibit unexpectedly quite different biological activities. Reaction of the cyanamide (92-1) from para-chloroaniline and cyanogen bromide with A-methylchloroacetamide (92-2) can be visualized to lead initially to the alkylation product (92-3). Cyclization by addition to the nitrile group then affords clazolamine (92-4) [98], a compound described as a diuretic. 

Various alkyl-substituted crown ethers have been prepared by cyclic addition across a double bond (e.g. bromination (77S854) or oxymercuration (80CC925)). Similarly, displacement of oligoethylene glycol dichlorides by cyanamide yields V-cyano monoaza crown ethers (81TL4105). 

Cyanamide and substituted cyanamides react with alcohols to give pseudoureas. Cyanamide reacts with alcohols in the presence of anhydrous hydrogen chloride, whereas disubstituted cyanamides require slightly more than an equivalent of sodium alkoxide for reaction with the alcohol. (See Tables III and IV.) Catalytic amounts of sodium alkoxides are sufficient to induce the reaction of a cyanamide with primary, secondary, or tertiary alcohols [21] (Eq. 17). When both R groups are secondary alkyl groups, alkaline catalysts... 

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