Triazines with 3 different substituent

Reaction of acylimidates with amidines affords a practical route to hitherto inaccessible 1,3,5-triazines with 3 different substituents. — E A soln. of cinnamoyl chloride in methylene chloride added dropwise below 0° during 0.5 hr. to a stirred soln. of isopropyl propionimidate and triethylamine in the same solvent, and stirring continued 20 hrs. at room temp. isopropyl N-cinnamoylpropionimidate (Y 83.1%) added to a stirred soln. of acetamidine hydrochloride in ferf-butanol previously treated at 35° with a mineral oil suspension of the equimolar amount of NaH, and stored 4 days at room temp. 

A route that allows the synthesis of 1,3,5-triazines with different substituents at each carbon is exemplified below - an A -acyl-iV,iV-dimethylamidme reacts with an amidine (shown) or guanidine to form a... 

The yields of the isolated trimers from mixed cyclotrimerization reactions is extremely variable and depends on the applied reaction conditions (catalyst system, molar ratio, temperature, pressure Table 7). Although the number of examples is limited, mixed cyclotrimerization is an advantageous tool for the one-step synthesis of a triazine with different substituents. 

Orange, red, and violet dyes can be obtained by using as coupling components aminonaphtholsulfonic acids that are connected via the N atom to a 1,3,5-triazine with different aminoalkylamino, trialkylammonium alkylamino, or cyclic ammonium substituents in the 4- and 6-positions [79], e.g., 27. Dye 28 dyes paper in a scarlet shade [80],... 

The skeletal structure common to the herbicides based on triazine is the s-triazine ring. Two of the three carbon atoms of the ring are substituted with alkylamino groups, while the third is substituted with a chlorine atom, or alkoxy or alkylmercapto groups. s-Triazine herbicides with different substituents are also known, although they have not yet attained any great importance. These will be discussed at the end of the chapter. 

Aromatic rings are characterized by sharp bands near 1600, 1580, 1500, and 1460 cm which may vary in intensity with different substituents. Pyridines are closely related to the benzene compounds. Triazines have strong bands in the 1600-1500 cm region. Heterocyclic compounds with two double bonds in a five-membered ring usually absorb at 1600-1530 and 1500-1430 cm"L... 

A different kind of triazine, 3,5,6-trisubstituted 1,2,4-triazines 166, were prepared by reaction of 1,2-diketones 164 with acyl hydrazide in the presence of ammonium acetate and acetic acid at 180 °C for 5 min under microwave irradiation in a sealed tube [107]. Different substituents can be introduced in the final triazines providing a general approach for this kind of heterocycles (Scheme 59). 

Triazines containing two different substituents are formed by a variety of methods. The guidelines described above are applicable to these compounds also (see Section 2.20.4.9.4). The condensation of imidates with amidines provides a valuable route to 6-substituted 2,4-dialkyl-l,3,5-triazines (see Section 2.20.4.6.2). 

Triazines with three different substituents are formed by variations on the above methods. There is no efficient route to trialkyl or triaryl derivatives, although the reaction of acylimidates and amidines has met with some success (see Section 2.20.4.6.2). In general the best routes available are as follows, (a) Substitution reactions of cyanuric chloride, (b) The condensation of Af-cyanoamidine with chloromethyliminium salts, (c) 2-Aryl-1,3,5-triazin-2-ones may be efficiently prepared by ring closure reactions on AT-(a-chloroalky-lidene)carbamoyl chloride and amidines (see Section 2.20.4.4.1). 

Cyclizations of acylamidines 720 with amidines 721 or guanidines in aprotic solvents give -triazines 722 bearing three different substituents (Scheme 309) <1995JOC8428>. 

More recently it has been reported that even A -acyl-A, A -dimethylcarboximidamide.s react with amidines or guanidines in aprotic solvents (t-BuOK, dioxane or THF, reflux, 3-16 h, 40 94%) to give 1,3,5-triazines with three different substituents.476... 

The reaction of A-acylimidates 17 or A-cyanoimidates 18 with amidines at room temperature also provides a route to 2,4,6-trisuhstituted 1,3,5-triazines with three different substituents.325,422,423 In the case of A-cyanoimidates 18, 4,6-disubstituted l,3,5-lriazin-2-amines 19 are obtained.422,423 Activated imidates 17 and 18 react with amidines under mild conditions in alcoholic solution to provide the 1,3,5-triazines.325,422,423 ln a similar reaction, A-cyano-carboximidamides condense with amidines to form 1,3,5-triazines however, more vigorous conditions are required.424... 

The reaction of A -acylthioamides or -(ethoxycarbonyljthioamides with various amidines allows the preparation of 1,3,5-triazines bearing two or three different substituents. Thus, jV-(ethoxycarbonyl)thioamides 30 react with the hydrochlorides of amidines or isothioureas in refluxing alcoholic solution in the presence of sodium alkoxide to yield disubstituted 1,3,5-tri-azin-2(l//)-ones 31.437... 

Among the 2-chloro-4,6-bis(alkylamino)-i-triazines with two different substituent side-chains, 2-chloro-4-ethylamino-6-isopropylamino-i-triazine (atrazine, 8) is the most active, and followed, in decreasing order of activity, by 2-chloro-4-ethylamino-6-5ec-butylamino-i-triazine (sebuthylazine, 9) and 2-chloro-4-ethyl-amino-6-/-butylamino-j-triazine (terbuthylazine, 10). 

Ultraviolet spectra of 1,2,4-triazines substituted with different hetero substituents (amino, oxo, thioxo) are also published <83JOC1271,86JHC33,89RRC1321>. 

Gas-phase IR spectra of 4,5,6-trifluoro- and 5-bromo-4,6-difluoro-l,2,3-triazine have been recorded, while KBr as matrix was used for 4,6-difluoro-5-iodo-, 4,5,6-trichloro-, and tribromo-l,2,3-triazine <1998TH1>. Slightly different frequencies had been reported earlier for the trichloro compound <1979CB1529>. IR data from KBr disks or liquid films of 1,2,3-triazines with various dialkylamino substituents have been reported <1979CB1529>, and IR frequencies of the following compound types are also available 2-oxides of alkylated and arylated 1,2,3-triazines... 

Cyclizations of acylamidines 180 with amidines 181 or guanidines 182 in aprotic solvents gave r-triazines 183 bearing three different substituents (Scheme 26) <1995JOC8428>. 

Cyclosilazane (R2SiNR) reacts with phenyl isocyanate at 60-90 °C to give the six-membered ring insertion products in high yield Silylated imines 289 react with one equivalent of isocyanate to give the insertion products 290, which on further reaction with a different isocyanate afford 5,6-dihydro-l,3,5-triazine-2,4(l//,3i/)-diones 291 with two different substituents . 

The kinetics of reaction of DABCO (7.66) and nicotinic acid (7.67 R = COOH) with the aminochlorotriazine dye Cl Reactive Red 3 (7.2) were studied under neutral conditions at temperatures in the range 100-130 °C. Quaternisation by DABCO was much more rapid than by nicotinic acid under these conditions. Neutral exhaust dyeing tests at 130 °C using the bis(aminochlorotriazine) analogue Cl Reactive Red 120 (7.48 X = Cl) with the two catalysts confirmed these trends, in that the degree of fixation was greatly increased by DABCO but nicotinic acid showed no appreciable catalytic effect [60]. This difference may be attributable to steric strain of the C-N+ bond in the quaternised triazine structure by the non-planar DABCO substituent. 

Comparison of this reactivity order with that found in the amination of 2-X-4-phenyl pyrimidines (SCH3 Br = Cl > F > SO2CH3 I > (013)3 > CN see Table 11.5 in Section ll,C,l,d) shows that these reactivity orders differ considerably. The fluoro substituent, especially, which has in the pyrimidine series about the same reactivity order as the chloro or bromo atom, shows in the 1,2,4-triazine series a low ANRORC activity. Comparison of both series of reactivities is, however, a delicate matter, mainly because the yields obtained for the amino compounds in the 1,2,4-triazine series are much lower than those obtained in the pyrimidine series, because of the occurrence of many side reactions, such as ring contraction, dehalogenation, ring transformations, and degenerate ring transformations... 

Alkylation and acylation of the different 1,2,4-triazine systems have also been extensively studied. Alkylation of 1,2,4-triazines (172) with methyl iodide gave mainly 1-methyl-1,2,4-triazinium iodides (173), which are red, and in a few cases the colourless 2-methyl isomers (174). The best results were obtained when nitromethane was used as the solvent for the alkylation. The formation of (173) or (174) depends on the substituents on the 1,2,4-triazine ring (63JCS1628). 

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