Anhydrobases

Even if the specific role attributed to benzothiazolium was not confirmed later (24), all these syntheses account for the significant and common behavior of quaternary salts, carbocations giving either symmetrical or asymmetrical reactive anhydrobases. They constitute the mam step in cyanine dye formation. 

A sufficient concentration of base B is necessary for the removal of a proton of the CH, group. In a first step, the equilibrium in Scheme 20 results, in which the monomeric anhydrobase Bi constitutes the conjugated base of the quaternary salt A,. As has been shown for other rings (24). the equilibrium depends upon the concentration of the different species and the relative strength of the bases B and Bj, and depends also upon the nature of X. 

Many monomeric heterocyclic anhydrobases can be isolated now using specific methods (44), but application of these methods to thiazole ring did not succeed however, appropriate conditions lead to the separation of a dimer, the structure of which has been established by its NMR Spectra and chemical reactivity (26). The most probable mechanism of its formation appears identical with the one previously described in the benzothiazolium series (24). A second molecule of quaternary salt A3... 

In a third step, the anhydrobase reacts on the carbon which is the most sensitive to nucleophilic attack. The unstable intermediate 23 splits into aminothiophenol and trimethine thiazolocyanine 124). 

Possibility of making 2-methyl benzothiazolium either bt reaction of the benzothiazolium quaternary salt on the anhydrobase (24) or by reaction of o-methylaminothiophenol on the same anhydrobase (26). 

When a quinaldinium salt and 2-unsubstituted thiazolium are condensed together in the presence of a basic agent, the resulting bis-(methylquinoline-2)trimethine cyanine is issued from the cleavage of the thiazolium ring of the anhydrobase (25). It is induced by the -CHj attack of quinaldinium according to a process already described (Scheme 28). 

Due to the structure of the symmetrical anhydrobase. every time a 2-methylthiazolium undergoes the attack of a base, theoretically it can result in two trimethine thiazolocyanines the mesomethylsubstituted one and the unsubstituted one. For an unexplained reason, it seems that when position 5 of the starting molecule is substituted, only the mesomethyl dye is produced according to the absorption spectrum, 530 nm for the methylmeso and 569 nm for the 4-phenyl substituted derivative (Scheme 29). ... 

The nucleophilic carbon of ketomethylene compounds can react with anhydrobases of different species in a basic medium. This reaction presents a narrow similitude with -CHj attack. The resulting dye, neut-rodimethine cyanine either mesomethyl-substituted or not. varies with the nature of the anhydro base (Scheme 30) (53. 54). 

Moreover, the specific role of anhydrobase in this condensation is not confirmed, since separated anhydrobases are not reactive toward aldehydes and the condensation can be made in an acid medium. 

A mesophenyl-substituted trimethine cyanine has been identified as a by-product in syntheses leading to styryl dyes it is also obtained when the anhydrobase reacts with the styryl dye (26). 

The reason for this relative lack of reactivity of 2-methylthiazoIium is probably due to the too-weak nucleophilic character of its carbon-2. For example, any /S-alkoxyalcene (29) derivatives resulting from the condensation of o-ester could never have been isolated, whereas they constitute the essential intermediate step in trimethine syntheses for rings of acidic character (64). However, even if a negative 5-substituent such as ethoxy-carbonyl increases the yield (61) by promoting independently the possible formation of the methylene base, it may be stressed that the presence of this base is not the essential condition of the reaction, since the isolated anhydrobase itself is not reactive toward the o-ester (Scheme 41). 

This derivative condenses either on itself (64) or on the anhydrobase, giving the trimethine dye. Indeed, the nucleophilic a-carbon of the dye—the proton is labile and can be replaced (70, 71)—is liable to add onto the electrophilic /3-carbon of the alcene derivative. The neocyanine results from elimination of a molecule of ethanol. 

Two moles of /3-alkoxyaicene can condense on each other by means of their a- and /3-carbon atoms. The resulting intermediate reacts on the anhydrobase by elimination of a molecule of ethanol resulting in a neocyanine formation (Schemes 59 and 60). Both monoanilino and bis-anilino derivatives resulting from the condensation of dimethylform-amide have been isolated. They are capable of furnishing various condensations on either ketomethylene or another reactive nucleus (Scheme 61). 

Rearrangement to an open chain imine (165) provides an intermediate whose acidity toward lithiomethylthiazole (162) is rather pronounced. Proton abstraction by 162 gives the dilithio intermediate (166) and regenerates 2-methylthiazole for further reaction. During the final hydrolysis, 166 affords the dimer (167) that could be isolated by molecular distillation (433). A proof in favor of this mechanism is that when a large excess of butyllithium is added to (161) at -78°C and the solution is allowed to warm to room temperature, the deuterolysis affords only dideuterated thiazole (170), with no evidence of any dimeric product. Under these conditions almost complete dianion formation results (169), and the concentration of nonmetalated thiazole is nil. (Scheme 79). This dimerization bears some similitude with the formation of 2-methylthia-zolium anhydrobase dealt with in Chapter DC. Meyers could confirm the independence of the formation of the benzyl-type (172) and the aryl-type... 

Die Anhydrobase vom 4-Hydroxy-2-methyl-cinnolinium-hydroxid liefert in Acetat-gepufferter Losung 4-Oxo-2-methyl-l,2,3,4-tetrahydro-cinnolin1 ... 

The asymmetrical anhydrobase (20) constitutes the first step of the formation of trimethine thiazolocyanine when a 2-methylthiazolium salt reacts either with a benzothiazolium or its opened form [which is bis-o-(formylmethylamino)(diphenyl disulfide] (Scheme 26). In a second step, 20 is protonated by a second molecule of 2-methylthiazolium. It results in cleavage of the benzothiazoline ring, which gives 21 together with the formation of the monomeric anhydrobase (22). Cleavage of the C-S bond of 20 can be explained by the important electronic desaturation of the C atom observed in NMR spectrum and the great polarizability of the C-S bond in this type of ring (48). 

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