Applications Alkylation

The anions of alkyl alkylthiomethyl sulfoxides have found broader application. Alkylation of the x-carbanion of methylsulfinyl(methylthio)methane with various haloalkanes and subsequent hydrolysis give aldehydes68. The use of ethylsulfinyl(ethylthio)methane leads to improved yields of alkylation products (>95%) 69. 

This class of surfactants has possibly the widest range of use of any anionic surfactant. It is found in almost every product where foaming is desirable, in industrial, household and personal care applications. Alkyl ether sulphates are described in terms of their parent alcohol and the degree of ethoxylation. Thus, sodium laureth-2 is the sodium salt of a sulphated (predominantly) C12 alcohol, with an average of 2 mol of ethylene oxide added. Often, the alcohol is assumed to be the typical C12-14 and the surfactant simply called a 2-or 3-mol ether sulphate. 

Applications. Alkyl ether sulphates are almost ubiquitous in cleaning products but are rarely found as the primary surfactant as they bring only some detergency but mainly contribute to foaming and viscosity building. 

In anionic solution systems the feed stocks are typically dried over various types of dessicants because the systems are sensitive to water contamination. When using continuous anionic solution polymerization systems, it is necessary to employ low (ppm) concentrations of a chain-transfer agent in order to discourage gelation and fouling 1,2-butadiene is often used for this purpose in commercial applications. Alkyl-lithium-initiated polybutadiene is less prone to contain gel and does not contain the heavy metal catalyst residues associated with Ziegler-Natta catalyzed products. 

As discussed earlier, polymer processing typically involves high temperatures, high shear fields and low oxygen concentrations, so that alkyl radicals will be expected to be the commonest species. In contrast, in end-use applications alkyl peroxy radicals are most common and hydroperoxides may be quite stable. 

One area of rapidly expanding interest is the use of reverse micellar systems of sugar-based surfactants in the extraction of proteins and other sensitive materials. The use of hydrophilic, nonionic, sugar-based surfactants for membrane protein extraction is well known to be effective due to the mild, nondenaturing properties of these surfactants when compared with ionic surfactants or polyoxyethylene derivatives. For the same reasons, protein extraction into reverse micellar systems is now becoming a popular medium for such applications. Alkyl sorbitan esters and ethoxylated sorbitan esters, such as Tween 85 [107] and Span 60 [108], have been used successfully to form reverse micellar systems for protein extraction. Blends of Tween and Span have also been found to be effective for this purpose [109]. More recently, commercially available sucrose fatty acid esters have been shown to form biocompatible reverse micellar systems into which cytochrome c is effectively extracted [110]. 

Applications. Alkyl ether sulfates constitute (with LAS and alkyl sulfates) one of the most important group among anionic surfactants. They are used in a broad spectrum of domestic applications such as household cleaners (e.g., carpet cleaners), dishwashing liquids, and fabric care (powders and liquids). 

It is very often the commercial interest in novel materials which stimulates the growth in their study and eventual exploitation. This is certainly true in the case of thermotropic liquid crystals and their application in electro-optic displays. Indeed, the production of high-strength, high-modulus fibres has seen a wealth of interest in lyotropic main chain polymers. The use of lyotropic side chain polymers has, by comparison, been less well publicized. This is not to say that there are no applications. Alkyl polyoxyethylene surfactants attached to polysiloxane polymers have found uses in many personal care products such as liquid soaps, shampoos, skin creams, and hair mousses. Unfortunately the physical properties of these and other similar materials have been closely guarded secrets and the amount of information available in the literature is low. The limited data which does exist, however, provides us with some interesting structure - behaviour relationships. 

Thermal stability. The tliennal stability of SAMs is, similarly to LB films, an important parameter for potential applications. It was found tliat SA films containing alkyl chains show some stability before an increase in tire number of gauche confonnations occurs, resulting in melting and irreversible changes in tire film. The disordering of tire... 

The above is a general procedure for preparing trialkyl orthophosphates. Similar yields are obtained for trimethyl phosphate, b.p. 62°/5 mm. triethyl phosphate, b.p. 75-5°/5 mm. tri-n-propyl phosphate, b.p. 107-5°/5 mm. tri-Mo-propyl phosphate, b.p. 83-5°/5 mm. tri-wo-butyl phosphate, b.p. 117°/5-5 mm. and tri- -amyl phosphate, b.p. 167-5°/5 mm. The alkyl phosphates are excellent alkylating agents for primary aromatic amines (see Section IV,41) they can also be ua for alkylating phenols (compare Sections IV,104-105). Trimethyl phosphate also finds application as a methylating agent for aliphatie alcohols (compare Section 111,58). 

The resulting alkyl 3 5-dinitrobenzoate may be employed for the characterisation of the ether. The method is only applicable to symmetrical or simple ethers a mixed aliphatic ether ROR would yield a mixture of inseparable solid esters. 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

We also found N-nitropyridinium salts such as C5HjN N02BF4 as convenient transfer nitrating reagents in selective, clean reaetions. Transfer nitrations are equally applicable to C- as well as to 0-nitra-tions, allowing, for example, safe, acid-free preparation of alkyl nitrates and polynitrates from alcohols (including nitroglycerine). 

In the synthesis of molecules without functional groups the application of the usual polar synthetic reactions may be cumbersome, since the final elimination of hetero atoms can be difficult. Two solutions for this problem have been given in the previous sections, namely alkylation with nucleophilic carbanions and alkenylation with ylides. Another direct approach is to combine radical synthons in a non-polar reaction. Carbon radicals are. however, inherently short-lived and tend to undergo complex secondary reactions. Escheirmoser s principle (p. 34f) again provides a way out. If one connects both carbon atoms via a metal atom which (i) forms and stabilizes the carbon radicals and (ii) can be easily eliminated, the intermolecular reaction is made intramolecular, and good yields may be obtained. 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

Two synthetic bridged nitrogen heterocycles are also prepared on a commercial scale. The pentazocine synthesis consists of a reductive alkylation of a pyridinium ring, a remarkable and puzzling addition to the most hindered position, hydrogenation of an enamine, and acid-catalyzed substitution of a phenol derivative. The synthesis is an application of the reactivity rules discussed in the alkaloid section. The same applies for clidinium bromide. 

In the last fifteen years macrolides have been the major target molecules for complex stereoselective total syntheses. This choice has been made independently by R.B. Woodward and E.J. Corey in Harvard, and has been followed by many famous fellow Americans, e.g., G. Stork, K.C. Nicolaou, S. Masamune, C.H. Heathcock, and S.L. Schreiber, to name only a few. There is also no other class of compounds which is so suitable for retrosynthetic analysis and for the application of modem synthetic reactions, such as Sharpless epoxidation, Noyori hydrogenation, and stereoselective alkylation and aldol reactions. We have chosen a classical synthesis by E.J. Corey and two recent syntheses by A.R. Chamberlin and S.L. Schreiber as examples. 

Since allylation with allylic carbonates proceeds under mild neutral conditions, neutral allylation has a wide application to alkylation of labile compounds which are sensitive to acids or bases. As a typical example, successful C-allylation of the rather sensitive molecule of ascorbic acid (225) to give 226 is possible only with allyl carbonate[l 37]. Similarly, Meldrum s acid is allylated smoothly[138]. Pd-catalyzed reaction of carbon nucleophiles with isopropyl 2-methylene-3,5-dioxahexylcarbomite (227)[I39] followed by hydrolysis is a good method for acetonylation of carbon nucleophiles. 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

Treatment of the borates with iodine leads to boron- C2 migration of an alkyl group[9]. This reaction has not been widely applied synthetically but it might be more applicable for introduction of branched alkyl groups than direct alkylation of an indol-2-yllithium intermediate. 

The appearance of the 2-(indol-3yl)ethylamine (tryptamine) unit in both tryptophan-derived natural products and in synthetic materials having potential pharmacological activity has generated a great deal of interest in the synthesis of such compounds. Several procedures which involve either direct 3-alkylation or tandem 3-functionalization/modification have been developed. Similarly, methodology applicable to preparation of tryptophan analogues has been widely explored. 

While both 2- and 3-vinylindole have been synthesized and characterized[l,2], they arc quite reactive and susceptible to polymerization. This is also true for simple l-alkyl derivatives which readily undergo acid-catalysed dimerization and polymerization[3]. For this reason, except for certain cases where in situ generation of the vinylindoles is practical, most synthetic applications of vinylindoles involve derivatives stabilized by EW-nitrogen substituents[4]. 

In this chapter we examine in turn the properties of alkyl and aryl-thiazoles that do not possess functional groups bonded directly to the thiazole ring. The general trends are underlined, and the applications of certains thiazole compounds in such areas as polymers, flavorings, and pharmacological and agricultural chemicals are discussed. 

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