1,3,5-Triazines trimerization

A large number of hindered phenoHc antioxidants are based on the Michael addition of 2,6-di-/ f2 -butylphenol and methyl acrylate under basic catalysis to yield the hydrocinnamate which is a basic building block used in the production of octadecyl 3-(3,5-di-/ f2 butyl-4-hydroxyphenyl)propionate, [2082-79-3], tetrakis(methylene-3(3,5-di-/ f2 butyl-4-hydroxylphenyl)propionate)methane [6683-19-8], and many others (63,64). These hindered phenolic antioxidants are the most widely used primary stabilizers in the world and are used in polyolefins, synthetic and natural mbber, styrenics, vinyl polymers, and engineering resins. 2,6-Di-/ f2 -butylphenol is converted to a methylene isocyanate which is trimerized to a triazine derivative... 

Strong bases, such as potassium acetate, potassium 2-ethylhexoate, or amine—epoxide combinations are the most useful trimerization catalysts. Also, some special tertiary amines, such as 2,4,6-tns(A7,A7-dimethylarninomethyl)phenol (DMT-30) (6), l,3,5-tris(3-dimethylaminopropyl)hexahydro-j -triazine (7), and ammonium salts (Dabco TMR) (8) are good trimerization catalysts. 

Organic Derivatives. Although numerous mono-, di-, and trisubstituted organic derivatives of cyanuric and isocyanuric acids appear in the hterature, many are not accessible via cyanuric acid. Cyanuric chloride 2,4,6-trichloro-j -triazine [108-77-0], is generally employed as the intermediate to most cyanurates. Trisubstituted isocyanurates can also be produced by trimerization of either aUphatic or aromatic isocyanates with appropriate catalysts (46) (see Isocyanates, organic). Alkylation of CA generally produces trisubstituted isocyanurates even when a deUberate attempt is made to produce mono- or disubstituted derivatives. There are exceptions, as in the production of mono-2-aminoethyl isocyanurate [18503-66-7] in nearly quantitative yield by reaction of CA and azitidine in DMF (47). 

Acetaldehyde ammonia trimer (hexahydro-2,4,6-trimethyl-l,3,5-triazine trihydrate) [76231-37-3] M 183.3, m 94-96 , 95-97 , 97 , b 110 (partly dec). Crystd from EtOH-Et20. When prepared it separates as the trihydrate which can be dried in a vacuum over CaCl2 at room temp to give the anhydrous compound with the same melting point. The dihydrate melts at 25-28° then resolidifies and melts again at 94-95°. IRRITATES THE EYES AND MUCOUS MEMBRANES. [J Org Chem 38 3288 1973.]... 

Triazines can be obtained either by condensation methods using the fluorinated anhydride (89IZV928) or by trimerization of nitriles, e.g., per-... 

Tribenzonitrile Dxide (2,4,6-Triphenyl-1,3,5-Triazine-Trioxide or Trimer Benzonitriloxide). (C H5)... 

A slightly related reaction involves nitriles, which can be trimerized with various acids, bases, or other catalysts to give triazines (see OS III, 71). HCl is most often used. Most nitriles with an a hydrogen do not give the reaction. 

Another versatile approach, which nicely complements these Mannich-based procedures, incorporates a preformed symmetrical hexahydro-l,3,5-triazine (HHT) intermediate. In this case the phosphorus reagent reacts with HHT as a trimeric form of the normal aldimine species generated in situ between the amine or amino acid and formaldehyde. These HHT reagents can often be puritied and isolated prior to the reaction with phosphites. They are reasonably stable under neutral or slightly basic conditions, but they can readily revert back to the original amine and formaldehyde after heating with aqueous acid (25). Several can be purchased commercially. 

Formamide is silylated on heating with HMDS 2 to give N,N-bis(trimethyl-silyl)formamide 22c, which trimerizes on continued heating to 140 °C to give s-triazine 1575, via 1573 and 1574, in 83% yield [78] (Scheme 9.47). 

Synthesis of the sym-Triazine System. I. Trimerization and Cotrimerization of Amidines. J. Amer. chem. Soc. 81, 1466 (1959)-... 

Another example of the remarkable reactivity of Mg actuated by our procedure is its reaction with nitriles. In this respect, the Mg resembles an alkali metal more than an alkaline earth. Benzonitrile reacts with Mg overnight, in refluxing DME, to give 2,4,6-triphenyl-l,3,5-triazine and 2,4,5-triphenylimidazole in 26 and 27% yield, respectively, based on magnesium. Jhe imidazole was shown to arise, at least in part, from the action of Mg on the triazine. The trimerization of aromatic nitriles to give symmetrical triazines is not unknown, but generally the reactions are... 

Benzonitrile is also trimerized to the s-triazine derivative by Raney nickel242 in a reaction which may proceed via the coordination compound (148)243 in a separate experiment this complex reacts with benzonitrile in the presence of benzamide to give the trimer (Scheme 171)242... 

The first species we will discuss is l,3,5-trimethylhexahydro-l,3,5-triazine (33, X = NMe). The gas-phase trimerization enthalpy of A-methylmethylenimine (34), reaction 41, has been evaluated53 to be —178 kJmol-1. 

The thermoset included here is derived from bisphenol-A dicya-nate. It can be thermally trimerized yielding a triazine or cyanurate network (8,9,10) as seen in the reaction scheme (Table 1). The critical molecular weight between crosslinks is relatively low, resulting in an extremely tight, brittle network. The material is usually used as a prepeg because a total cure produces a hard, infusible, and insoluble matrix. It possesses excellent adhesive properties and is currently used as a metal coupling agent. It offers many superior properties relative to conventional epoxies derived from bisphenol-A. 

Triazines (60) have been prepared by reaction of KOCN with an alkyl chloride, involving trimerization of alkyl isocyanate intermediates formed in solid-liquid PTC.109... 

The electrochemical oxidation of isobutyraldehyde98 and acetaldehyde99 in methanol-ammonia, containing lithium chloride, yields s-triazines through formation of an iminomethoxy adduct, RC(=NH)OCH3, followed by trimerization with liberation of methanol. No s-triazine is obtained from formalin, and benzaldehyde gives only a 1% yield of s-triazine. Cyana-mide has also been oxidized at a platinum anode in aqueous potassium hydroxide.100 The oxidation products consisted of several known products,... 

Trimerization of imidates is a valuable route to 1,3,5-triazines. Imidates can be considered as activated nitriles and cyclotrimerize more readily. Most symmetrical 2,4,6-trialkyl-1,3,5-triazines are easily formed, although large alkyl substituents may give rise to steric hindrance (61JOC2778). Symmetrical isocyanurates (525) are readily available from isocyanates, RNCO catalysts include tertiary amines, phosphines and sodium methoxide. Aldehydes RCHO and ammonia give hexahydro-1,3,5-triazines (526), known as aldehyde ammonias (73JOC3288). 

The 1,3,5-triazines are all synthesized by nucleophilic substitution of cyanuric chloride, which in turn is made by trimerization of cyanogen chloride. As each chlorine is replaced, the reactivity of the remaining ones diminishes. Thus the first displacement takes place at room temperature or below, the second requires moderate heat and the third needs strong heating (Scheme 1). The chemistry of the triazine herbicides has been reviewed (B-75MI10700, B-60MI10700). 

Cyclopropenes react very easily with 1,2,4-triazines. The azanorcaradienes (378), or their valence tautomers, the 4//-azepines (379), were isolated via the tricyclic intermediates (380) and loss of nitrogen. The equilibrium between (378) and (379) depends on the substituents. The 4//-azepines rearrange to the 3//-compounds (381) (80TL595, 72JA2770). The parent 1,2,4-triazine (1) also reacts with cyclopropene, but the product seems to be a trimer of the azanorcaradiene, of uncertain structure (70UP21901). 

Probably the cyclotrimerization of nitriles is the best known route to 1,3,5-triazines. The reaction has the obvious limitation that it is of value for preparing the symmetrical derivatives only. Nevertheless, many important triazines, such as cyanuric chloride, are made in this way. There are a number of other cyclotrimerization reactions which are also useful, in particular the trimerization of imidates. An easy route to 1,3,5-triazine from ammonium acetate has been developed. 

Base-catalyzed trimerizations are facile also for example, trifluoromethyl cyanide trimer-izes in the presence of ammonia, presumably through the formation of the amidine intermediate (139 Scheme 77) (67JOC231). Similarly, perfluoro-n-propyl cyanide forms the 1,3,5-triazine in the presence of sodium methoxide, probably via the imidate (140 Scheme 78) (52JA5633). 

The preparation of 1,3,5-triazine 1,3,5-trioxides by trimerization of a nitrile oxide was reported (09CB803) however, the structure of the product has been reassigned as a polymer (65LA(687)191>. 

Substituted amidines are of limited use in the synthesis of symmetric 1,3,5-triazines. Only formamidine or amidines bearing strongly electron withdrawing groups react readily. The proposed mechanism (59JA1466) resembles that of the trimerization of imidates (Scheme 87). 

The trimerization of imidazole derivatives is the best known route to fused 1,3,5-triazines by formation of three carbon-nitrogen bonds. A typical example is shown in equation 81 (75BCJ956). Takeuchi et al. investigated the trimerization of 2-fluoroimidazoles, and found... 

There are few examples of this type of synthesis. Typically, an azirine reacts with isocyanates or isothiocyanates to yield the triazine via a series of dipolar intermediates. The products may be contaminated with the isocyanate trimer the example of Scheme 114 below is typical. The novel spiro compound (188) is formed by a similar route (Scheme 115) (79HCA1429, 81LA264). 

In this context it is interesting to note that benzonitrile, Ph—C=N, trimerizes to a triazine on a Raney nickel surface. It was assumed that Jt-bonded nitriles were involved in the reaction mechanism.10 This reaction resembles the well-known template synthesis of phthalocyanine complexes from phthalodinitrile. Formation of linear polymers [—C(R)—N—] occurs on heating aryl or alkyl cyanides with metal halides.11... 

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