N-Tosylamides

The synthesis of 11 (an analogue of 7 in which its 12-membered cyclen had been replaced by 14-membered cyclam rings) was reported in 1998 using the tri-N-tosylamide derivative of cyclam and l,3,5-tris(bromomethyl)benzene as precursors [24], The trinuclear Hg(II) derivative was shown to selectively recognise and bind a tripodal tris(histidine) ligand in which the three (S)-histidines are 12 A apart. The system was seen as a model for peptide recognition. 

The reaction of secondary sulfonamides with carboxylic acids in the presence of DCC and4-pyrrolidinopyridine affords N-tosylamides. Also intramolecular cyclization to lactames is achieved using DCC. 

Sulfonamide acridinium derivatives have been utilized as signal labels for sensitive immunoassays because of their stability and high chemiluminescence yield. Two acridinium derivatives, N-sulfopropyl N-tosylamide acridinium [Acr or Acr(spcp)] and N,N-disulfopropyl N-p-(3-carboxypropyl)phenylsulfonamide acridinium [Acr(spsp)], were used in our conjugates.4 Their structures and chemiluminescence reaction mechanism are illustrated in Fig 1. 

Conjugates of Acridinium and MAb Anti-HCV core. Acr-cll-10 IgG (Control Conjugate). Monoclonal antibody (MAb) cl 1-10 anti-HCV core IgG was directly labeled with N-hydroxysuccinimide ester of N-sulfopropyl N-tosylamide acridinium (Fig 1) in a phosphate buffer. After conjugation, the conjugate was separated by sec-HPLC into fractions with Acr/IgG molar ratios ranging from 3 to 5 estimated by A370 and A28o-... 

Acr-BSA and activation with SMCC. Bovine albumin (BSA) was labeled with active ester of N-sulfopropyl N-tosylamide acridinium in a phosphate buffer. Acr-BSA was separated from free acridinium through a disposable G-25 column. Multiple lots of Acr-BSA were made and their Acr/BSA ratios ranging from 10 to 25 were estimated by A370 and A28o. Acr-BSA was activated with LC-SMCC active ester (Pierce Biotech, Rockford, IL, USA) in a phosphate buffer. The LC-SMCC linked Acr-BSA was separated from free SMCC with a G-25 column. 

Dialkylation of an amine or sulfonamide with a 1,3-dihalide provides a further route to azetidines <79CRV33l, 64HC( 19-2)88 5). Examples of this approach are the formation of N-tosylazetidine from tosylamide and l-bromo-3-chloropropane and the formation of N-alkylazetidinyl esters (36). The latter reaction works well except for R=Me the former provides a useful route to azetidine since the tosyl group can be removed by reductive methods. 

Die kathodische Reduktion von N,N-Dichlor-tosylamid fiihrt zum entsprechenden Ni-tren, in Gegenwart von 1,4-Dioxan entsteht neben Tosylamid (Graphit-Kathode, max. 90% d.Th.) bis zu 32% d.Th. (Platin) 2-Tosylamino-J,4-dioxan (in Acetonitril/Lithium-perchlorat)3. 

The reaction can be done intramolecularly. N-Benzyl pent-4-ynamide reacted with tetrabutylammonium fluoride to an alkylidene lactam. Similar addition of a tosylamide-alkene, with a palladium catalyst, led to a vinyl Al-tosyl pyrrolidine. Similar cyclization reactions occur with tosylamide-alkynes. ... 

Hydroaminomethylahon of alkenes [path (c)j wiU not be considered [12]. This review deals exclusively with the hydroaminahon reaction [path (d)], i.e. the direct addition of the N-H bond of NH3 or amines across unsaturated carbon-carbon bonds. It is devoted to the state of the art for the catalytic hydroamination of alkenes and styrenes but also of alkynes, 1,3-dienes and allenes, with no mention of activated substrates (such as Michael acceptors) for which the hydroamination occurs without catalysts. Similarly, the reachon of the N-H bond of amine derivatives such as carboxamides, tosylamides, ureas, etc. will not be considered. 

Propargylated tosylamides also isomerize efficiently [221, 281]. On the other hand, rare examples are propargylated hydrazines [251], N-propargylated imines [282], isonitriles (must be N-propargylated) [283], ammonium salts [284] and azides [285],... 

The nucleophilic addition of lithiated methoxyallene to N-tosylimines delivers tosylamides 174. Treatment of the latter with AgN03 leads cleanly to dihydropyrroles 175, which under acidic conditions provide pyrrolidin-3-ones 176. Another example is the reaction of 177 to 178 (Scheme 15.55) [113]. 

Yu and co-workers have expanded upon Ojima s work through development of an effective Rh-catalyzed protocol for the cyclization/hydrosilylation of allenyl carbonyl compounds to form silylated vinylcycloalkanols and heterocyclic alcohols.For example, reaction of tosylamide 44 (X = NTs, R = H, n= ) and triethylsilane catalyzed by Rh(acac)(GO)2 (1 mol%) under GO (10 atm) at 70 °G for 8h gave the silylated vinyl pyrrolidinol 45 (X = NTs, R = H, n= ) in 74% yield with exclusive formation of the m-diastereomer (Equation (29)). The rhodium-catalyzed reaction was also effective for the cyclization of alleneones and for the formation of carbocycles, oxygen heterocycles, and six-membered cyclic alcohols (Equation (29)). However, Rh-catalyzed cyclization/hydrosilylation of allenyl carbonyl compounds that possessed substitution on an allenyl carbon atom was not established (Equation (29)). The efficiency of the Rh-catalyzed reaction of allenyl carbonyl compounds depended strongly on GO pressure. Reactions run under 10 atm GO were more efficient than were... 

While extended reaction times (up to three days) have not been found to be detrimental, it is critical that the temperature of the reaction be maintained at 120°C. Above 130°C, N-dealkylation of the macrocyclic ring accompanies hydrolysis of the tosylamide group, yielding a nearly intractable mixture of mono- and dialkylated ligands. 

Sulfonamides can also be alkylated by support-bound electrophiles (Table 8.10). Polystyrene-bound allylic alcohols have been used to N-alkylate sulfonamides under the conditions of the Mitsunobu reaction. Oxidative iodosulfonylamidation of support-bound enol ethers (e.g. glycals Entry 3, Table 8.10) has been used to prepare /V-sulfonyl aminals. Jung and co-workers have reported an interesting variant of the Baylis-Hillman reaction, in which tosylamide and an aromatic aldehyde were condensed with polystyrene-bound acrylic acid to yield 2-(sulfonamidomethyl)acrylates (Entry 4, Table 8.10). 

Intramolecularity was the next issue to be probed within the context of alkynyliodonium salt/nucleophile addition reactions.53 1 No prior history was available to guide us, and so the prospects for success remained uncertain. Of primary concern was the potential for iodonium salt/base destructive interactions in competition with the desired N-H deprotonation reaction. A substrate that bore some resemblance to key portions of the agelastatin precursor 33 was prepared (Scheme 6), compound 39. This species duplicated the alkynyliodonium/"amide" pairing of the real system, but it lacked the complex piperazine carbene trap of 33. The tosylimide (pre)nucleophile was proposed as a compromise between what we really wanted (an N-methyl amide) and what would likely work (a tosylamide). Simple treatment of 39 with mild base effected the desired bicyclization to afford the tosylimide product 41 in decent yield. A transition state model 40 for C-H insertion that features an equatorial phenyl unit might rationalize the observed sense of diastereoselectivity. So, at least for 39, no evidence for possible interference by iodonium/base reactions was detected. 

Iron salts (e.g. FeCls) have been identified as new catalysts for intramolecular hydroamination. A number of olefinic tosylamides underwent the reaction at 80 °C to form the corresponding the N-tosylpyrrolidine derivatives in good yield.63 The same salt can also catalyse Markovnikov addition of electron-rich arenes and heteroarenes to styrenes, giving rise to 1,1-diarylalkanes at 80 °C.64... 

Anions of secondary-sulfonamides, especially N-substituted tosylamidate ions, have emerged as premier partners for C-N bond forming reactions with alkynyliodonium salts. To a much lesser extent secondary-carboxamidate ions have also been used for this purpose. For example, the sequential treatment of -substituted tosylamides with n-butyllithium and phenyl(trimethylsi-lylethynyl)iodonium triflate (26) affords the corresponding N-trimethylsi-lylethynyl-p-toluenesulfonamides, which can be desilylated with tetrabutylam-monium fluoride in wet THF (Scheme 51) [ 151 ]. It is noteworthy that the presence of such groups as n-Bu and CH2 = CH(CH2)2- in the tosylamidate ions did... 

Reactions of phenyl(propynyl)iodonium triflate (30) with tosylamidate ions possessing N-alkyl chains of two or more carbon atoms follow the carbene insertion pathway leading to AT-tosyldihydropyrroles 31 (Scheme 54) [154,155]. The N-cyclohexyl tosylamidate ion leads stereospecifically to the ds-fused bicyclic dihydropyrrole under these conditions. 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

The selective consecutive cycloisomerization/isomerization of 1,6-dienes to form exocyclic and then endocyclic olefinic compounds is not a common transformation. At 80 °C, with RuCl2(p-cymene)(N-mesitylmethylbenzi-midazole) activated by reaction with diphenylpropynol in the presence of AgOTf as the catalyst, as an attempt to generate allenylidene intermediate, diallyl tosylamide is selectively transformed into 3-mclhyl-4-mclhylene-N-tosylpyrrolidine. When this catalytic cycloisomerization is completed, the isomerization into 3,4-dimethyl-AMosylpyrrolidine starts without external modification of the catalytic system (Scheme 27) [68]. 

There is also a palladium(O) catalytic route involving formation of the 3-3a bond assembly of an N-aUcynyl-orf/to-iodoaniline-tosylamide is followed by exposure to the catalyst and an amine, which becomes incorporated into the indole at C-2. ... 

The reaction of sodium tosylamide (or tosylamide in the presence of base) with the ditosylate ester of triethylene glycol gave N,Al -ditosyldiaza-18-crown-6 in 9% or 77% yields depending on reaction conditions, while the dichloro starting material gave a 15% yield of the diaza-crown (method... 

Benzenesulfonamide, N-ethyl-4-methyl- CCRIS 6037 EINECS 201-275-1 Ethyl tosylamide N-Ethyl-4-methylbenzenesulfonamide N-Ethyl-p-methylbenzene-sulfonamide N-Ethyl-4-... 

When the electrolysis medium is rendered more and more basic, one may note a splitting of the step and its shift to more cathodic values. Excesses of a strong base lead to total deactivation of the tosylamide. On the other hand, the addition of phenol permits the occurrence of a four-electron step where the two N-Ts bonds are cleaved simultaneously. 

It -L. i. v with tosylamide anions to provide iic " cJiates. When a nucleofugal group ivc" -n point, automatic elimination gives a - H Tid leads to an indole. 

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