1.3.5- Triazines cyanuric chloride

Fig. 8.n Covalent coupling of trypsin to a silicon surface. In a first step, free silanol groups are reacted with 3-amino-propyltriethoxysilane. The amino-functionalized surface is then treated with 2,4,6-trichloro-1,3,5-triazine (cyanuric chlorid). Finally, trypsin is covalently bound via a free amino group of the protein. 

Before embarking on a discussion of recent developments in 1,3,5-triazine chemistry, it is appropriate to look at the 1,3,5-triazines in their historical context. Thus, the original syntheses and characterization of four of the more important compounds, 1,3,5-triazine, cyanuric chloride, cyanuric acid and melamine, will be discussed briefly. 

In addition to being the most valuable starting material for the 1,3,5-triazines, cyanuric chloride has been used for the preparation of alkyl halides, acid chlorides, peptides, dicarbodiimides and macrocyclic lactones (see Section 2.20.3.12.2). 

Galactosidase has been attached to glass in this way.56 The immobilized enzyme is useful in removing lactose from milk, for the benefit of those persons who are intolerant of lactose. A similar technique was used to attach glucose oxidase to magnetite (I i O-i) particles, starting with a trimethoxysilane.57 This permits easy separation with a magnet. The immobilized enzyme was 50% less active than the native enzyme, but kept 95% of its activity after 9 months at 4°C. Another way to attach an enzyme to a support is to treat the metal oxide support first with 2,4,6-trichloro 1,3,5 triazine (cyanuric chloride) (5.18), then with the enzyme.58 This was done on both alumina and on silica. 

A variety of oximes 255 undergo the Beckmann rearrangement upon treatment with 2,4,6-trichloro-l,3,5-triazine (cyanuric chloride, 256) in A,A-dimethylformamide (DMF, 257) at room temperature in excellent yields (equation 77). 

Trichloro-l,3.5-triazine (cyanuric chloride, 5) can be converted using a sixfold excess of sulfur tetrafluoride at 250 C into 2,4,6-trifluoro-l,3,5-triazine (cyanuric fluoride, 6) with lower proportions of sulfur tetrafluoride, cyanuric chlorofluorides are formed.191... 

For the preparation of the symmetrically substituted 2-chloro-4,6-bis(alkyl-amino)-5-triazines, cyanuric chloride, suspended in the solvent-water mixture, is reacted with the amine in two temperature steps (0-5°C and 40-45°C) in the presence of inorganic acid acceptor (Pearlman and Banks, 1948 Thurston el ai, 1951 Gysin and Kniisli, 1959). Asymmetric 2-chloro-4,6-bis(alkylamino)-5-triazines (ametryne, sebuthylazine, terbuthylazine) can be synthesised in two reaction steps without the formation of symmetrical analogues. In the first step, the... 

A more recent modification was reported by Giacomelli and De Luca wherein oxalyl chloride has been replaced by 2,4,6-trichloro[l,3,5]triazine (cyanuric chloride, TCT) as the activator.16 The authors cite the dangerous toxicity and moisture sensitivity of oxalyl chloride as a motive for their work, the exclusion of which also means that the reaction can be carried out between -30 and 0 °C. Alcohols and. V-protected a-amino alcohols were converted to the corresponding ketones and aldehydes. 

Column 250 x 4.6 CSP-4 (Prepare as follows. Add a solution of 1.07 g L-valyl-L-valyl-L-valine isopropylester (Bunseki Kagaku 1979, 28, 125) in 30 mL dry dioxane (Caution Di-oxane is a carcinogen ) dropwise to a mixture of 2.2 g2,4,6-trichloro-l,3,5-triazine(cyanuric chloride) in 20 mL dry dioxane stirred at 0°, add 3 g anhydrous sodium carbonate at room temperature, stir, filter, evaporate to give a colorless solid. Dissolve 8.3 g of this solid in 30 mL dry dioxane, add 2 g N-(2-aminoethyl)-3-aminopropyltrimetho3ysilane, add 1.5 g anhydrous sodium carbonate, reflux with stirring for 40 h, filter, add 3 g dried 10 p.m Li-Chrosorb Si 100, reflux with slow stirring for 10 h, cool, filter. Wash the solid with dioxane, MeOH, and diethyl ether, dry imder reduced pressure (J.Chromatogr. 1984, 292, 427).) Mobile phase Hexane 1,2-dichloroethane EtOH trifluoroacetic acid 62.5 35 0.625 0.25 Detector UV... 

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). 

Cyanuric chloride (TCT, 2,4,6-trichloro-l,3,5-triazine) [108-77-0] M 184.4, m 146-149 , 154 , h 190 . Crystd from CCI4 or pet ether (b 90-100°), and dried under vacuum. Recrystd twice from anhydrous benzene immediately before use [Abuchowski et al.J Biol Chem 252 3582 1977]. 

Flament et al made use of the partial replacement of two chlorine atoms in cyanuric chloride (12) with methoxyl groups, the 2,4-di-methoxy-6-chloro-l,3,5-triazine (13) formed was dehalogenated to 2,4-dimethoxy-1,3,5-triazine (14) and this yielded the product (2) on gentle hydrolysis. 

Goi. As noted previously, an a-chlorine atom renders a ring-nitrogen atom very weakly basic. Cyanuric chloride (5) is a very weak base both because s-triazines are of low basicity and because each of the ring-nitrogen atoms is alpha to two chlorine atoms. Hence, this compound should be insensitive to acid catalysis or acid autocatalysis and this has been observed for the displacement of the first chlorine atom with alcohols in alcohol-acetone solution and with water (see, however. Section II,D,2,6). 

The reactivity of cyanuric chloride (2,4,6-trichloro-s-triazine) as an indication of s-triazine activation is misleadingly high because of mutual activation of the chlorines meta activation > ortho or para activation) and its symmetry (cf. Section III,A, 1), However, the greatest variety of nucleophilic substitutions have been investigated with this substrate. 

Even polyalkoxy-s-triazines are quite prone to nucleophilic substitution. For example, 2,4,6-trimethoxy-s-triazine (320) is rapidly hydrolyzed (20°, dilute aqueous alkali) to the anion of 4,6-dimethoxy-s-triazin-2(l )-one (331). This reaction is undoubtedly an /S jvr-4r2 reaction and not an aliphatic dealkylation. The latter type occurs with anilines at much higher temperatures (150-200°) and with chloride ion in the reaction of non-basified alcohols with cyanuric chloride at reflux temperatures. The reported dealkylation with methoxide has been shown to be hydrolysis by traces of water present. Several analogous dealkylations by alkoxide ion, reported without evidence for the formation of the dialkyl ether, are all associated with the high reactivity of the alkoxy compounds which ai e, in fact, hydrolyzed by usually tolerable traces of water. Brown ... 

Because of the high polarity of the C=N double bonds, cyanuric chloride (120, R= Cl) is comparable with a carboxylic acid chloride. This explains its smooth reaction with diazomethane to yield dichloro-(diazomcthyl)-l,3,5-triazine (121, R = The analogous com-... 

Preparation of Reagent and Labelling Procedures. The structure of F-D [2-(2,4-diazobicyclo-2,2,2-octyl)-4-(5-aminofluoresceinyl)-6-morpholinyl 1,3,5-triazine] has been confirmed by its FAB-MS, IR, and H-NMR spectra (9). Briefly, F-D was synthesized by the treatment of fluorescamine isomer I with cyanuric chloride, then reaction with morpholine and DABCO (l,4-diazobicyclo-2,2,2-octane), as illustrated... 

It also follows that protonation of the triazine ring makes it more susceptible to attack by nucleophilic reagents unless the reagent itself is also protonated. If the triazine ring remains unprotonated when a nucleophilic base, such as an alkylamine, is present as its acid salt the reaction is slower, of course. Cyanuric chloride itself is a very weak base that becomes protonated only under strongly acidic conditions. Thus step 1 in Scheme 11.2 can be carried out in aqueous solution even at pH 2 without risk of undesirable hydrolysis of cyanuric chloride, water being an extremely weak nucleophile. 

DAST-type FBAs may contain by-products (such as 11.13) derived from hydrolysis of one or more of the chloro substituents in cyanuric chloride (11.10). One such troublesome byproduct is 2,4-bis(anilino)-6-hydroxy-s-triazine (11.62). Not only is this compound environmentally undesirable, it may also interact with certain bleaching agents and its presence can lead to the development of unpleasant odours on storage of a detergent... 

---