Quaternary formation

Patyk-Kara, N.G., Gorelikova, N.V., Plakht, J., Nechelyustov, G.N. Chizhova, I.A. (1997) Desert varnish as an indicator of the age of Quaternary formations (Makhtesh Ramon Depression, Central Negev). Transactions (Doklady) of the Russian Academy of Sciences/Earth Science Sections 353A, 348-351. 

A soln. of 2-benzyl-4-cresol in toluene added gradually to a suspension of NaH in toluene, refluxed 30 min., and to the gently refluxing soln. so obtained / -dimethylaminoethyl phloride, dissolved in toluene, added dropwise —2-benzyl-4-tolyl-y3-dimethylaminoethyl ether. Y 89%.—In the case of phenols containing a basic function, only the theoretical amount of the chloride was used in order to minimize quaternary formation (p. 3795). (F. e. s. W. B. Wheatley, L. C. Cheney, and S. B. Binkley, Am. Soc. 71, 64, 3795 (1949).)... 

Girard s reagent P , C5H5NCH2C0NHNH2 C1. In a 1-htre threenecked flask, equipped as in the previous preparation, place 200 ml. of absolute ethyl alcohol, 63 g. (64 -5 ml.) of pure anhydrous pyridine and 98 - 5 g. (84 5 ml.) of ethyl chloroacetate. Heat the mixture under reflux for 2-3 hours until the formation of the quaternary salt is complete acidify a small test-portion with dilute sulphuric acid it should dissolve completely and no odour of ethyl chloroacetate should be apparent. Cool the mixture in ice and salt. Replace the thermometer by a dropping funnel, and add a solution of 40 g. of 100 per cent, hydrazine hydrate in 60 ml. of absolute ethanol all at once. A vigorous exothermic reaction soon develops and is accompanied by vigorous effervescence. The pro duct separates almost immediately. When cold, filter with suction, wash... 

Allylic amine is a less reactive leaving group[7], but the allylic ammonium salts 214 (quaternary ammonium salts) can be used for allylalion(l30,131]. Allylic sulfonium salts are also used for the allylation[130]. The allylic nitrile in the cyclic aminonitrile 215 can be displaced probably via x-allylic complex formation. The possibility of the formation of the dihydropyridinium salts 216 and subsequent conjugate addition are less likelyfl 32],... 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

A-4-Thiazoline-2-ones and ring substituted derivatives are usually prepared by the general ring-closure methods described in Chapter II. Some special methods where the thiazole ring is already formed have been used, however. An original synthesis of 4- 2-carboxyphenyl)-A-4-thiazoline-2-one (18) starting from 2-thiocyanato-2-halophenyl-l-3-indandione (19) has been proposed (Scheme 8) (20, 21). Reaction of bicyclic quaternary salts (20) may provide 3-substituted A-4-thiazoline-2-one derivatives (21) (Scheme 9) (22). Sykes et al. (23) report the formation of A-4-thiazoline-2-ones (24) by treatment ef 2-bromo (22) or 2-dimethylaminothiazole (23) quaternary salts with base (Scheme 10). 

In 1923, Mills introduced thiazole for the first time in the synthesis of methine dyes through a somewhat indirect route. In order to demonstrate the 2,4 -cyanine mechanism of formation by quinoline and quinaldine quaternary salts reacting together, Mills used other pairs of quaternary salts as 2-methylthiazolium with either quinolinium or benzothiazolium (42, 43). 

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. 

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... 

The methine chain is obtained by reacting ethyl o-formate (method A ) or ethylisoformanilide (method B) with a bis quaternary salt of bis-(2-thiazolyllbutane. Concerning dyes with fused thiazolo rings pyrrolo[2. lb]thiazoIe. thiazolo[2.3a]indole. thiazolo[2.3c]1.4-benzox-azine. the a carbon directly linked to the carbon 2 of the thiazoJe ring is also responsible for the classical syntheses giving trimethine or penta-methine dyes. 

Manufacture. For the commercial production of DPXN (di-/)-xylylene) (3), two principal synthetic routes have been used the direct pyrolysis of -xylene (4, X = Y = H) and the 1,6-Hofmaim elimination of ammonium (HNR3 ) from a quaternary ammonium hydroxide (4, X = H, Y = NR3 ). Most of the routes to DPX share a common strategy PX is generated at a controlled rate in a dilute medium, so that its conversion to dimer is favored over the conversion to polymer. The polymer by-product is of no value because it can neither be recycled nor processed into a commercially useful form. Its formation is minimised by careful attention to process engineering. The chemistry of the direct pyrolysis route is shown in equation 1 ... 

The nitro alcohols available in commercial quantities are manufactured by the condensation of nitroparaffins with formaldehyde [50-00-0]. These condensations are equiUbrium reactions, and potential exists for the formation of polymeric materials. Therefore, reaction conditions, eg, reaction time, temperature, mole ratio of the reactants, catalyst level, and catalyst removal, must be carefully controlled in order to obtain the desired nitro alcohol in good yield (6). Paraformaldehyde can be used in place of aqueous formaldehyde. A wide variety of basic catalysts, including amines, quaternary ammonium hydroxides, and inorganic hydroxides and carbonates, can be used. After completion of the reaction, the reaction mixture must be made acidic, either by addition of mineral acid or by removal of base by an ion-exchange resin in order to prevent reversal of the reaction during the isolation of the nitro alcohol (see Ion exchange). 

A number of cationic muds have been developed and used. These ate formulated around quaternary amines or positively charged polymers (108,109). The polymer in some iastances may be a cationic polyacrylamide. Poly(dimethylarnine-fi9-epichloiohydrin) is another material that has been used successfiiUy for drilling shale formations (110,111). Some of these additives may requite a salt such as sodium or potassium chloride for best results. 

The substantial decrease of polyacrylamide solution viscosity in mildly saline waters can be uti1i2ed to increase injection rates. A quaternary ammonium salt polymer can be added to the polyacrylamide solution to function as a salt and reduce solution viscosity (144). If the cationic charge is in the polymer backbone and substantially shielded from the polyacrylamide by steric hindrance, formation of an insoluble interpolymer complex can be delayed long enough to complete polyacrylamide injection. Upon contacting formation surfaces, the quaternary ammonium salt polymer is adsorbed reducing... 

Complex Ion Formation. Phosphates form water-soluble complex ions with metallic cations, a phenomenon commonly called sequestration. In contrast to many complexing agents, polyphosphates are nonspecific and form soluble, charged complexes with virtually all metallic cations. Alkali metals are weakly complexed, but alkaline-earth and transition metals form more strongly associated complexes (eg, eq. 16). Quaternary ammonium ions are complexed Htde if at all because of their low charge density. The amount of metal ion that can be sequestered by polyphosphates generally increases... 

The addition of P—H bonds across a carbonyl function leads to the formation of a-hydroxy-substituted phosphines. The reaction is acid-cataly2ed and appears to be quite general with complete reaction of each P—H bond if linear aUphatic aldehydes are used. Steric considerations may limit the product to primary or secondary phosphines. In the case of formaldehyde, the quaternary phosphonium salt [124-64-1] is obtained. 

Salt formation with Brmnsted and Lewis acids and exhaustive alkylation to form quaternary ammonium cations are part of the rich derivati2ation chemistry of these amines. Carbamates and thiocarbamates are formed with CO2 and CS2, respectively the former precipitate from neat amine as carbamate salts but are highly water soluble. 

Mass spectral analysis of quaternary ammonium compounds can be achieved by fast-atom bombardment (fab) ms (189,190). This technique rehes on bombarding a solution of the molecule, usually in glycerol [56-81-5] or y -nitroben2yl alcohol [619-25-0], with argon and detecting the parent cation plus a proton (MH ). A more recent technique has been reported (191), in which information on the stmcture of the quaternary compounds is obtained indirectly through cluster-ion formation detected via Hquid secondary ion mass spectrometry (Isims) experiments. 

Dialkyldimethyl and alkyltrknethyl quaternaries can be prepared direcdy from secondary and primary amines as shown ia equations 7 and 8, respectively. This process, known as exhaustive alkylation, is usually not the method of choice on a commercial scale. This technique requires the continuous addition of basic material over the course of the reaction to prevent the formation of amine salts (223,224). Furthermore, products such as inorganic salt and water must be removed from the quaternary. The salt represents a significant disposal problem. 

Nitrile Intermediates. Most quaternary ammonium compounds are produced from fatty nitriles (qv), which are ia turn made from a natural fat or oil-derived fatty acid and ammonia (qv) (Fig. 2) (see Fats AND FATTY oils) (225). The nitriles are then reduced to the amines. A variety of reduciag agents maybe used (226). Catalytic hydrogenation over a metal catalyst is the method most often used on a commercial scale (227). Formation of secondary and tertiary amine side-products can be hindered by the addition of acetic anhydride (228) or excess ammonia (229). In some cases secondary amines are the desired products. 

The reaction of higher alkyl chlorides with tin metal at 235°C is not practical because of the thermal decomposition which occurs before the products can be removed from the reaction zone. The reaction temperature necessary for the formation of dimethyl tin dichloride can be lowered considerably by the use of certain catalysts. Quaternary ammonium and phosphonium iodides allow the reaction to proceed in good yield at 150—160°C (109). An improvement in the process involves the use of amine—stannic chloride complexes or mixtures of stannic chloride and a quaternary ammonium or phosphonium compound (110). Use of these catalysts is claimed to yield dimethyl tin dichloride containing less than 0.1 wt % trimethyl tin chloride. Catalyzed direct reactions under pressure are used commercially to manufacture dimethyl tin dichloride. 

The presence of ammonia during hydrogenation suppresses formation of secondary amines and inhibits hydrogenation of double bonds in unsaturated nitriles. Eatty amines are used as corrosion inhibitors, flotation agents, quaternary salts for sanitizing agents and textile fabric softeners, and surface-active agents. 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

Finally, a novel synthetic route involves formation of the pyridine ring from a fused pyran intermediate, e.g. (139) - (140) (70CB1250, 80JOC1918, 73JCS(P1)823). If a pyrylium salt is used, a quaternary pyridopyrimidinium salt such as (141) is formed 77KGS14S4). 

Dimethylaminopyrazoles react with alkylating agents to afford quaternary salts (72BSF2807). The nitrogen atom of the dimethylamino group is the most reactive in the case of 3-dimethylamino- and 4-dimethylamino-pyrazoles (formation of 456 and 457 salts, respectively) whereas 5-dimethylaminopyrazoles yield aminopyrazolium salts (458). 

Treatment of 2-isoxazolines with acid usually leads to ring rupture and formation of chalcone products 62HC(l7)l), although 5-methyl-3-phenyl-2-isoxazoline forms a quaternary salt with dimethyl sulfate in the presence of perchloric acid (Scheme 51) (73BSF1390). 

Although there is very little scope for reactions of the above types with 1,2-benzisoxazole derivatives, the quaternary salts such as 2-methyl-3-phenyl-l,2-benzisoxazolium salt underwent base-catalyzed isomerization to the 1,3-benzoxazine shown in Scheme 83. This reaction is analogous to the formation of (202) above (67AHC(8)277). 

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