Quinacridone syntheses

Quinacridone pigments are manufactured commercially by two distinct processes The original thermal or solvent process developed at DuPont and the more widely utiUzed polyphosphoric acid (PPA) process. Each process, with its own inherent advantages and disadvantages, differs significantly from the other but shares a common feature, the key starting material dimethyl succinoylsuccinate (DMSS) 7. Because of its crucial status in the manufacture of quinacridone pigments the synthesis of 7 also merits some discussion. 

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During the past 50 years, approximately 150 differently substituted quinacridones, synthesized by utilization of the above and other more complicated methods, have been reported in an extensive list of patents and other publications. 

The typical quinacridone synthesis may be exemplified by the manufacture of unsubstituted quinacridone. 

Analysis of PPA demonstrates that it is composed mainly of phosphoric acid tetramers (from hydrolysis of P4O10), as illustrated in Scheme 18.11. During the initial stage of quinacridone synthesis, reaction with a terephthalic acid 17 results in the formation of phosphate esters. A bis-diphosphate (bis-pyrophosphate) ester species 23 is displayed in the reaction scheme although a variety of combinations of mono- to triphosphate esters could and probably do form and probably equilibrate with each other also, in the hot acid. However, due to the symmetry of the tetrameric phosphoric acid and the known nucleofugic propensity of a diphosphate moiety, bis-diphosphate esters such as 23 probably form preferentially as reactive intermediates and by analogy, diphosphate esters would be expected to significantly facilitate the cycUzation process. 

Solid solution products also may be formed during the quinacridone synthesis stage by incorporation of the appropriate intermediates in the desired ratios. Generally this cosynthesis method is better suited to the PPA manufacturing process, e.g., PR 282 (see Section 18.4). 

Fig. 3. Synthesis of quinacridones where (1) is dialkyl 2,5-diarylamino-3,6-dihydroterephthalate. See Table 6 for representative groups.

Practical methods for synthesis and elucidation of the optimum physical forms were developed at Du Pont (13). The violets fill the void in the color gamut when the inorganics are inadequate. The quinacridones may be used in most resins except polymers such as nylon-6,6, polystyrene, and ABS. They are stable up to 275°C and show excellent weatherabiUty. One use is to shade phthalocyanines to match Indanthrone Blue. In carpeting, the quinacridones are recommended for polypropylene, acrylonitrile, polyester, and nylon-6 filaments. Predispersions in plastici2ers ate used in thermoset polyesters, urethanes, and epoxy resins (14). 

Quaternary ammonium compounds biocidal activity mechanism, 1, 401 toxicity, 1, 124 Quaternization heterocyclic compounds reviews, 1, 73 ( )-Quebrach amine synthesis, 1, 490 Queen substance synthesis, 1, 439 4, 777 Quercetin occurrence, 3, 878 pentamethyl ether photolysis, 3, 696 photooxidation, 3, 695 Quercetrin hydrolysis, 3, 878 Quinacetol sulfate as fungicide, 2, 514 Quinacridone, 2,9-dimethyl-, 1, 336 Quinacridone pigments, 1, 335-336 Quinacrine... 

The synthesis of linear turns-quinacridone (2.38) was reported in 1935 by Liebermann [26] and was cursorily looked at as a red vat colorant but not developed commercially. It was more than twenty years later that the DuPont company introduced these compounds as pigments under the trade name of Cinquasia. Their chemical structures are based on Cl Pigment Violet 19 (2.38). As with the phthalocyanines, this compound can exist in several polymorphic forms in this case there are three, termed a-, p- and y- forms only the last two being useful as pigments. The first three pigments were called Cinquasia Red B (y-form, size above 1000 nm), Cinquasia Red Y (y-form, size below 1000 nm) and Cinquasia Violet R (P-form). 

The chemical synthesis of linear turns-quinacridones and their substituted derivatives that have been marketed subsequently is a complicated multi-stage sequence, making such pigments very expensive and sustainable only where high-fastness red pigments are essential, as in the car industry. There are four routes of synthesis, details of which have been given by Pollack [27]. 

In the manufacture of quinacridone pigments only the first and last of the four routes outlined have been operated commercially. Synthesis is followed by the milling processes necessary to give products with the crystal structure and particle size required for their use as pigments. 

Several synthetic pathways for the commercial manufacture of quinacridone pigments have been published. In this context, only those routes are mentioned which were developed for industrial scale production. There are four options, the first two of which are preferred by the pigment industry. It is surprising to note that these are the methods which involve total synthesis of the central aromatic ring. On the other hand, routes which start from ready-made aromatic systems and thus might be expected to he more important actually enjoy only limited recognition. 

Among syntheses which start from preformed aromatic systems, the Sandoz process in particular has stimulated interest. It is the only route which allows the manufacture of asymmetrically substituted quinacridones. A typical synthesis follows. 

The synthesis of quinacridone 8-1 was first claimed in a series of papers beginning in 1896 (Niementowski 1896, 1906 Ullman and Maag 1906 Baczynski and Niementowski 1919) all of which later proved to be an angular isomer of the linear compound first prepared in 1935 (Lieberman 1935 Liebermanefa/. 1935). Little was done with the compound until 1955 when Du Pont chemists recognized its polymorphic behaviour and associated favourable photochemical stability (Jaffe 1992). Jaffe has also noted that many acridone derivatives are polymorphic. Additional relevant references may be found in the recent review by Lincke (2000). 

Several methods of synthesis of the quinacridones are reported. Each of these involves several stages, accounting at least in part for the somewhat higher cost of these pigments. The two most important methods to the parent compound are outlined in Scheme 4.11. In both routes, the starting material, diethyl succinylsuccinate, 4.42,... 

Quinacridones 114,258 chemical structure 280 Quinacridoneequinone 292 IF synthesis, new 293 IF synthesis, old 293 IF Quinacridone Pigments 178, 279, 374 Quinacridone Reds 122 and 202 415 Quinaldine 307... 

Today two commercial synthetic routes are available for the manufacture of quinacridone pigments and some substituted derivatives. The key starting material in either synthesis is dialkyl sucdnoylsucdnate (7), which is synthesized from dialkyl succinate in the presence of a sodium alkoxide catalyst, usually sodium methoxide. The first step is a Claisen condensation, and this is followed by a Dieckman cydization, yielding the disodium salt 8, which upon addification yields 7 (Scheme 18-2)1 1... 

Scheme 18-4. Synthesis of quinacridones via 2,5-diaryiaminoterephthaiic acids (PPA process).

Still another synthesis, which yields moderate yields of 11, is based on the Ullmann reaction of 2,5-dibromo- or 2,5-dichloroterephthalic acids or esters with aromatic amines (Scheme 18-5) l This approach is suitable for the preparation ofunsymmetri-cally or monosubstituted quinacridones by a two-step reaction sequence which allows the isolation of 2-halo-5-aryl-aminoterephthalic acid (13) for subsequent reaction with a different amine. Although the yields are moderate the resulting terephthalic adds (14) can be cyclized by the same methods described earlier. For a short period, 2-methylquin-acridone (15, R=2-methyl) was commercialized by Sandoz. 

Thus far, we have considered substitution in the peripheral benzene rings only. Quinacridonequinone can be considered, in a general sense, as a 6,13-derivative. In fact, this quinone was the first compound ever synthesized with the true linear quinacridone ring system . The method employed for its synthesis was the addition of... 

The name quinacridone first coined by Niementowski [1] in 1896 and attributed to the compound 1 was obtained by reaction of phloroglucinol with anthranihc acid. Although a linear isomer of 1 was assumed to have formed also, it was demonstrated [2] subsequently that the presumed mixture consisted entirely of the angular isomer 1. In 1906, it was erroneously claimed [3] that Unear quinacridone 2 in the form of yeUow crystals resulted from cycUzation of l,4-bis(o-carboxyanilino) benzene 3 in concentrated sulfuric acid. Years later, the product was demonstrated to be the angular isomer 4 (Scheme 18.1) [4]. The first authentic example of the Unear quinacridone ring system was demonstrated by Sharvin [5] by the synthesis of quinacridonequinone (QAQ) 5. Other claims to the synthesis of Unear trans-quinacridone 2 were either demonstrated or presumed to be erroneous. 

Experimental data from various Uterature sources indicate that the maximum yield of DMSS is approximately 80% relative to the quantity of methoxide utilized, regardless of the reaction solvent employed in its synthesis. Various attempts to improve the yield efficiency and consequently the economics of quinacridone production have been ineffective but have resulted in the discovery of some of the competing side reactions based on the identification the corresponding isolated by-products. Therefore, it is of interest to consider the latter and the potential modes of their formation. 

It is important to note that the by-products are minimized during DMSS synthesis and/or eliminated during the separation stage. Any persisting residues then will be eliminated during the subsequent stages of quinacridone production (thermal or PPA) ensuring no contribution to impurity formation in the final products. 

The alternative commercial process for manufacturing quinacridones, the PPA process, also commences with DMSS 7 which is converted to 12 by acid-catalyzed reaction with the appropriate aromatic amines in water miscible alcohol solvents. Generally without isolation, the dihydrodiester 12 is oxidized by some of the agents described for the oxidation of the dihydroquinacridone 16 and hydrolyzed by base in the aqueous alcohol solvents to the water soluble disodium 2,5-diaryl-aminotere-phthalates that when acidified afford excellent yields of the corresponding 2,5-diaryl-aminoterephthalic acids 17. Typically this 3-stage synthesis is conducted as a 1-pot process [18] (Scheme 18.9). 

Compared to the thermal process, quinacridone production in PPA occurs at significantly lower temperatures (120-140 °C) utilizing the already oxidized intermediates (diarylaminoterephthalic acids, 17) to synthesize the crude products directly. Therefore, excluding the synthesis of DMSS, production of most quin-... 

Scheme 18.17 Synthesis of quinacridone via 2,5-dichloro-3,6-diethoxy-carbonyl-1,4-benzoquinone.

The Chapman rearrangement also has been applied to the synthesis of the parent quinacridone as well as other derivatives not readily accessible by other methods. However, this synthesis is mostly of theoretical interest and at present has no manufacturing utility. 

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