Amines monoalkylation

ETS-10 is a titanosilicate with a three-dimensional 12-ring pore system and a very high ion-exchange capacity. The integral heats of adsorption of monoalkyl-amines on ETS-10 have been measured by isothermal calorimetry as a funchon of the n-alkylamine concentrahon [118]. The heats vary in the order methyl < ethyl < propyl < butyl amine. 

Treatment of a primary amine with an equimolar amount of an alkylating agent and a base generally produces a mixture of an N-monoalkylated amine (1) and an N,N-dialkylated amine (2) (2/). However, the cooperative function of weakly acidic and weakly basic sites on zeolites, together with steric demands by the zeolite cavities, brought about selective N-monoalkylation of... 

The synthesis of phosphazenium compounds is based on the reaction of phosphorus pentachloride with various dialkyl and monoalkyl amines [34-38, 144-146]. Other phosphazenium compounds catalytically active in anionic PO and EO polymerisation, are ... 

In 2015, Kempe and co-workers reported the first cobalt-catalyzed A-alkylation of (hetero)arylamines with alcohols under mild conditions (80 °C) with a relatively low catalyst loading (2 mol%) (Elq. 32) [133]. In 2016, Zhang and co-workers developed another pincer cobalt complex 19, which is an active catalyst for both imination and A-alkylation reactions of aromatic and aliphatic amines with alcohols under base-free conditions [134]. By using complex 19, monoalkylated amine products rather than the imines can be selectively achieved by simply adding 4 A molecular sieves to the reaction mixture (Eq. 33). 

An exception to the usual formation of radical-derived products in the presence of amines is a recent report that irradiation of 1-bromo- (41b) and 1-chloroadamantane (41c) and 1-chloronorbornane (8c) in the presence of primary amines afforded the substitution products 156 and 157, along with the radical products adamantane (42) and an adamantyl dimer or norbornane (9) and a norbomyl dimer.However, the quantum yields were very small (2-4 x 10 for chloride 41b and 6 x 10" for chloride 8c), and neither the chemical yields of the products nor the relative yields of substitution and radical products were reported. Likewise, no comment was provided on the formation of monoalkyl amine intermediates. Since these amines are primary, electron transfer within the charge-transfer complex may occur less readily. 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

The single largest market use for quaternary fatty amines is in fabric softeners. Monoalkyl quaternaries (chloride) have been used in Hquid detergent softener antistat formulations (LDSA), dialkyl dimethyl quaternaries (chloride) in the rinse cycle, and dialkyl dimethyl quaternaries (sulfate) as dryer softeners. 

MonoaLkylation using small alkyl groups of the 1-, 2 - and 3 -amines tends to reduce potency somewhat, whereas alkylation of the 3-amino group reduces activity considerably (147). 1-/V-Alkylation, as in the case of 1-A[-acylation, can lead to resistance to some bacterial resistance reactions, eg,... 

FORSTER - DECKER Amine Synthesis Selective monoalkylation of primary amines via imines An altemativa method is the reaction ol 1 and 2 in the preserve of NaCNBH4 or tnaceloxyborohydride (Borch reduction)/... 

A trifluoromethylsulfonamide can be prepared from a primary amine to allow monoalkylation of that amine. ... 

A trifluoromethylsulfonamide can be prepared from a primary amine to allow monoalkylation of that amine. The triflamide is not stable to strong base, which causes elimination to an imine, but when used to protect an indole, it is cleaved with K2CO3 in refluxing methanol. ... 

Unfortunately, these reactions don t stop cleanly after a single alkylation has occurred. Because ammonia and primary amines have similar reactivity, the initially formed monoalkylated substance often undergoes further reaction to yield a mixture of products. Even secondary and tertiar) amines undergo further alkylation, although to a lesser extent. For example, treatment of 1-bromooctane with... 

The development of monoalkyl phosphate as a low skin irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste and liquid-type skin cleansers, and also phosphorylation reactions from the viewpoint of industrial production [26]. Amine salts of acrylate ester polymers, which are physiologically acceptable and useful as surfactants, are prepared by transesterification of alkyl acrylate polymers with 4-morpholinethanol or the alkanolamines and fatty alcohols or alkoxylated alkylphenols, and neutralizing with carboxylic or phosphoric acid. The polymer salt was used as an emulsifying agent for oils and waxes [70]. Preparation of pharmaceutical liposomes with surfactants derived from phosphoric acid is described in [279]. Lipid bilayer vesicles comprise an anionic or zwitterionic surfactant which when dispersed in H20 at a temperature above the phase transition temperature is in a micellar phase and a second lipid which is a single-chain fatty acid, fatty acid ester, or fatty alcohol which is in an emulsion phase, and cholesterol or a derivative. 

Alcohols can be converted to amines in an indirect manner. The alcohols are converted to alkyloxyphosphonium perchlorates which in DMF successfully monoalkylate not only secondary but also primary amines. ... 

When enamines are treated with alkyl halides, an alkylation occurs that is analogous to the first step of 12-14. Hydrolysis of the imine salt gives a ketone. Since the enamine is normally formed from a ketone (16-12), the net result is alkylation of the ketone at the a position. The method, known as the Stork enamine reaction is an alternative to the ketone alkylation considered at 10-105. The Stork method has the advantage that it generally leads almost exclusively to monoalkylation of the ketone, while 10-105, when applied to ketones, is difficult to stop with the introduction of just one alkyl group. Alkylation usually takes place on the less substituted side of the original ketone. The most commonly used amines are the cyclic amines piperidine, morpholine, and pyrrolidine. 

Monoalkylation of Af-tosylallylamine 10 with dibromoalkane 101 proceeded in 60-90% yield (Eq. 10 see also Scheme 3 and Eq. 2) [17]. The bromoalkyl-amines 102 were converted to nitro compounds 103. In situ transformation of 103 into nitrile oxides led to spontaneous cycloaddition with formation of isox-azolines fused to 5-, 6-, and 7-membered ring heterocycles 104 a-c. Under very high dilution conditions, 103 d was converted to 104 d, an isoxazoline fused to an 8-membered azocine, in low (10%) yield. 

Compound (1) phosphorylates phosphate monoesters and alcohols, although with the latter a considerable excess of alcohol is necessary to obtain satisfactory yields. In the absence of mercuric ions the milder phosphorylating species (3) can be isolated which converts monoalkyl phosphates to pyrophosphate diesters in good yield but does not react appreciably with alcohols unless catalytic amounts of boron trifluoride are added. Amine salts of (3) are converted to phosphoramidates on heating. In the presence of silver ions, O-esters of thiophosphoric acid behave as phosphorylating agents and a very mild and convenient procedure suitable for preparing labile unsymmetrical pyrophosphate diesters, such as the... 

Even with a limited amount of the alkylating agent, the equilibria between protonated product and the neutral starting amine are sufficiently fast that a mixture of products may be obtained. For this reason, when monoalkylation of an amine is desired, the reaction is usually best carried out by reductive amination, a reaction that is discussed in Chapter 5. If complete alkylation to the quaternary salt is desired, use of excess alkylating agent and a base to neutralize the liberated acid normally results in complete reaction. 

Benzhydrylamine Derivatives Attachment of piperazine nitrogen directly to a benzhydryl carbon leads to a pair of compounds which show vasodilator activity, and which should be useful in disease states marked by impaired blood circulation. Reaction of piperonyl chloride (18) with a mixture of piperazine and piperazine dihydrochloride leads to the monoalkylation product (19). (It may be supposed that the mixture of free base and salt equilibrates to the monobasic salt, thus making the second amine less nucleophilic.) Alkylation of 19 by means of benzhydryl chloride then... 

Most studies of micellar systems have been carried out on synthetic surfactants where the polar or ionic head group may be cationic, e.g. an ammonium or pyridinium ion, anionic, e.g. a carboxylate, sulfate or sulfonate ion, non-ionic, e.g. hydroxy-compound, or zwitterionic, e.g. an amine oxide or a carboxylate or sulfonate betaine. Surfactants are often given trivial or trade names, and abbreviations based on either trivial or systematic names are freely used (Fendler and Fendler, 1975). Many commercial surfactants are mixtures so that purity can be a major problem. In addition, some surfactants, e.g. monoalkyl sulfates, decompose slowly in aqueous solution. Some examples of surfactants are given in Table 1, together with values of the critical micelle concentration, cmc. This is the surfactant concentration at the onset of micellization (Mukerjee and Mysels, 1970) and can therefore be taken to be the maximum concentration of monomeric surfactant in a solution (Menger and Portnoy, 1967). Its value is related to the change of free energy on micellization (Fendler and Fendler, 1975 Lindman and Wennerstrom, 1980). 

In summary, primary amine and monoalkyl derivatives of tryptamine have not yet been demonstrated to produce hallucinogenic effects in man or to consistently produce profound behavioral effects in animals. Admittedly, relatively few compounds have been examined, and few studies have been conducted. Nevertheless, present evidence suggests that these derivatives, by virtue of their inability to penetrate the blood-brain barrier and/or their rapid metabolism, may not be able to achieve adequate brain levels to elicit effects. In some cases, these factors may lead to masking of potential central effects by peripheral actions of the compounds or their metabolites. 

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