Methyl-substituted amidine

Ring opening by photolysis also occurs in the oxadiazoline ring. Srivastava and Clapp109 noted that a simple rearrangement [Eq. (44)] of 4-/3-ethoxyethyl-3-methyl-5-p-nitrophenyl-l,2,4-oxadiazoline to a substituted amidine (50) took place on a bench top in ordinary daylight or... 

Chloro- and methyl-substituted acetic and propionic acids Amide, thioamide, and amidine herbicides Amides Ureas... 

Some ferrocenylphosphine-amidine ligands (Figure 3.6) with central and planer chirality were prepared and their efficiency and diastereomeric impact in the palladium catalysed asymmetric allylic substitution were examined [75]. Up to 96% ee with 98% yield was achieved by the use of a ligand with a methyl-substituted ligand. 

Lithium n-propylmercaptide in hexamethylphosphoramide provides a mild system for the rapid dealkylation of quaternary ammonium salts, with high propensity for methyl group removaL. Substituted amidines have been prepared under very mild conditions from nitriles, halides, and amines with the help of a Lewis acid such as ferric chloride . a,a-Dichloro-/ -ketoesters undergo a rapid fragmentation with nucleophiles, even with relatively weak ones such as diethylamine, and can thus serve as acylating agents... 

Cyanopyridazines add ammonia, primary and secondary amines and hydroxylamine to give amidines or amidoximes. Substituted amides, thioamides and carboximidates can be also prepared. With hydrazine, 3-pyridazinylcarbohydrazide imide is formed and addition of methylmagnesium iodide with subsequent hydrolysis of the imine affords the corresponding pyridazinyl methyl ketone. 

Substituted pyrimidine N-oxides such as 891 are converted analogously into their corresponding 4-substituted 2-cyano pyrimidines 892 and 4-substituted 6-cya-no pyrimidines 893 [18]. Likewise 2,4-substituted pyrimidine N-oxides 894 afford the 2,4-substituted 6-cyano pyrimidines 895 whereas the 2,6-dimethylpyrimidine-N-oxide 896 gives the 2,6-dimethyl-4-cyanopyrimidine 897 [18, 19] (Scheme 7.6). The 4,5-disubstituted pyridine N-oxides 898 are converted into 2-cyano-4,5-disubsti-tuted pyrimidines 899 and 4,5-disubstituted-6-cyano pyrimidines 900 [19] (Scheme 7.6). Whereas with most of the 4,5-substituents in 898 the 6-cyano pyrimidines 900 are formed nearly exclusively, combination of a 4-methoxy substituent with a 5-methoxy, 5-phenyl, 5-methyl, or 5-halo substituent gives rise to the exclusive formation of the 2-cyanopyrimidines 899 [19] (Scheme 7.6). The chemistry of pyrimidine N-oxides has been reviewed [20]. In the pyrazine series, 3-aminopyrazine N-ox-ide 901 affords, with TCS 14, NaCN, and triethylamine in DMF, 3-amino-2-cyano-pyrazine 902 in 80% yield and 5% amidine 903 [21, 22] which is apparently formed by reaction of the amino group in 902 with DMF in the presence of TCS 14 [23] (Scheme 7.7) (cf. also Section 4.2.2). Other 3-substituted pyrazine N-oxides react with 18 under a variety of conditions, e.g. in the presence of ZnBr2 [22]. 

N-Methyl-AT-(substituted phenyl )formamidine was reacted with EMME in boiling toluene for 3 hr to give amidine derivatives (193) in poor yields (80EUP15440). 

Tertiary benzylic nitriles are useful synthetic intermediates, and have been used for the preparation of amidines, lactones, primary amines, pyridines, aldehydes, carboxylic acids, and esters. The general synthetic pathway to this class of compounds relies on the displacement of an activated benzylic alcohol or benzylic halide with a cyanide source followed by double alkylation under basic conditions. For instance, 2-(2-methoxyphenyl)-2-methylpropionitrile has been prepared by methylation of (2-methoxyphenyl)acetonitrile using sodium amide and iodomethane. In the course of the preparation of a drug candidate, the submitters discovered that the nucleophilic aromatic substitution of aryl fluorides with the anion of a secondary nitrile is an effective method for the preparation of these compounds. The reaction was studied using isobutyronitrile and 2-fluoroanisole. The submitters first showed that KHMDS was the superior base for the process when carried out in either THF or toluene (Table I). For example, they found that the preparation of 2-(2-methoxyphenyl)-2-methylpropionitrile could be accomplished h... 

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))... 

Substituted malondialdehydes form pyrimidines substituted in the 5-position with an alkyl, aryl, halo, or hetero substituent. The pyrimidine is unsubstituted in the 4- and 6-positions. /3-Dialdehyde equivalents are frequently used in these reactions, for example, 3-alkoxy- or 3-aminoacroleins. With aldehydo ketones, the pyrimidine carries a substituent in the 4- or 6-position. The formyl group in the ketone is normally masked as an alkoxymethylene ketone or as an aminomethylene ketone. A commonly used procedure involves the preparation of a dimethylaminomethyl-ene ketone 645 by reaction of a methyl ketone 644 with DMF dimethylacetal and subsequent reaction with an amidine or guanidine to form the target pyrimidine 646 <2003MI237, 2004JHC461>. 

The kinetics and mechanism of the phosphorus-catalysed dimerization of acrylonitrile to give 1,4-dicyanobut-l-ene and 2,4-dicyanobut-l-ene have been studied.114 The reactions of aryhminodimagnesium (138) with //-substituted p-cyanobenzophenones, l-cyano-9-fluorenenone, o-, m-, and p-dicyanobcnzcnes, and o-, m-, and p-nitrobenzonitriles have been examined.115 The effect of pressure on the reaction of 3 -methyl- l-(4-tolyl)triazene (139) and benzoic acid in chloroform and acetonitrile has been studied.116 The effect of acids on the rate of urethane formation from alcohols and isocyanates in the presence of alkyltin carboxylates has been examined.117 A Hammett a value has been reported for the amidine group N=CHNMe2 and used for the prediction of the basicity of sites in bifunctional amidines.118... 

Well leveling azo dyes are also obtained when pyrazolones substituted in the 1-position by an amidine residue are used as coupling components. The diazo components are predominantly substituted by methyl and methoxyl groups [6], An example is 2 [68936-08-3]. 

Treatment of A-[l-(dimethylamino)ethylidene]benzenecarboselenoamide (103) with ethyl bromopyruvate in the presence of triethylamine affords 5-[(ethoxy carbonyl)acetyl]-4-methyl-2-phenyl-l,3-selenazole (104) (Scheme 31) [179], In a similar reaction of morpholino(selenocarbonyl)-amidines with 2-(chloromethyl)-5-nitrothiophene other substituted 1,3-selenazoles were obtained [180],... 

Reaction of l,2,3,6,7,116-hexahydro-4//-pyrazino[2,l-a]isoquinoline with H2NCN, KCNO in 5% HC1, and MeCN in the presence of A1C13 gave the 2-amidine, aminocarbonyl, and 2-(l-iminoethyl) derivatives, respectively (65BEP659249). A 2-substituted derivative was also obtained from the reaction of 1,2,3,6,7,llh-hexahydro-4//-pyrazino[2,l- ]isoquinolin-4-one and 3-methyl-5-nitro-2-furaldehyde oxime (84MI1). 

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... 

---