Triethylamine N-oxide

Triethylamine, 61,83,87,88,94,99,100,112 Triethylamine N-oxide, 84 Triethylbenzylammonium chloride, 49 Triethylsilane, 104,127.128 Trifluoroacetic acid, 59 Trimethyi-m-dimethylaminophenylsilane, 40 Trimethyl orthoformate, 109... 

Problem 18.60 Synthesize the following compounds from alcohols of four or fewer C s, cyclohexanol and any needed solvents and inorganic reagents, (a) n-hexylamine, (h) triethylamine N-oxide, (c) 4-(N-methylamino)heptane, (d) cyclohexyldimethylamine, (e) cyclopentylamine, (/) 6-aminohexanoic acid. 

A number of symmetrically substituted cyclopentadienone metal complexes have been prepared by metalcarbonyl-mediated dimerization of alkynes [23a, 24]. The (tetracyclopropylcyclopentadienone)tricarbonyliron complex 27 can easily be obtained as the major product by ironcarbonyl-mediated dimerization with CO insertion of dicyclopropylacetylene [25]. Upon treatment of the complex 27 with triethylamine N-oxide, the uncomplexed tetracyclopropylcy-clopentadienone 28 apparently is liberated however, in contrast to the kineti-cally sufficiently stabilized tetra-ferf-butylcyclopentadienone 19 (see Scheme 5)... 

Accordingly, cyclic nitronates can be a useful synthetic equivalent of functionalized nitrile oxides, while reaction examples are quite limited. Thus, 2-isoxazoline N-oxide and 5,6-dihydro-4H-l,2-oxazine N-oxide, as five- and six-membered cyclic nitronates, were generated in-situ by dehydroiodination of 3-iodo-l-nitropropane and 4-iodo-l-nitrobutane with triethylamine and trapped with monosubstituted alkenes to give 5-substituted 3-(2-hydroxyethyl)isoxazolines and 2-phenylperhydro-l,2-oxazino[2,3-fe]isoxazole, respectively (Scheme 7.26) [72b]. Upon treatment with a catalytic amount of trifluoroacetic acid, the perhydro-l,2-oxazino[2,3-fe]isoxazole was quantitatively converted into the corresponding 2-isoxazoline. Since a method for catalyzed enantioselective nitrone cycloadditions was established and cyclic nitronates should behave like cyclic nitrones in reactivity, there would be a good chance to attain catalyzed enantioselective formation of 2-isoxazolines via nitronate cycloadditions. 

Substituted pyrimidine N-oxides such as 891 are converted analogously into their corresponding 4-substituted 2-cyano pyrimidines 892 and 4-substituted 6-cya-no pyrimidines 893 [18]. Likewise 2,4-substituted pyrimidine N-oxides 894 afford the 2,4-substituted 6-cyano pyrimidines 895 whereas the 2,6-dimethylpyrimidine-N-oxide 896 gives the 2,6-dimethyl-4-cyanopyrimidine 897 [18, 19] (Scheme 7.6). The 4,5-disubstituted pyridine N-oxides 898 are converted into 2-cyano-4,5-disubsti-tuted pyrimidines 899 and 4,5-disubstituted-6-cyano pyrimidines 900 [19] (Scheme 7.6). Whereas with most of the 4,5-substituents in 898 the 6-cyano pyrimidines 900 are formed nearly exclusively, combination of a 4-methoxy substituent with a 5-methoxy, 5-phenyl, 5-methyl, or 5-halo substituent gives rise to the exclusive formation of the 2-cyanopyrimidines 899 [19] (Scheme 7.6). The chemistry of pyrimidine N-oxides has been reviewed [20]. In the pyrazine series, 3-aminopyrazine N-ox-ide 901 affords, with TCS 14, NaCN, and triethylamine in DMF, 3-amino-2-cyano-pyrazine 902 in 80% yield and 5% amidine 903 [21, 22] which is apparently formed by reaction of the amino group in 902 with DMF in the presence of TCS 14 [23] (Scheme 7.7) (cf. also Section 4.2.2). Other 3-substituted pyrazine N-oxides react with 18 under a variety of conditions, e.g. in the presence of ZnBr2 [22]. 

The N-oxide of l-pyrrolo[2,3-b]pyridine 936 is converted by the combination tri-methylsilylisothiocyanate Me3SiNCS 937/MeOCOCl to 21% 6-isothiocyanato-l-methoxycarbonyl-pyrrolo[2,3-b]pyridine 938 and 18% 6-chloro-l-methoxycarbonyl-pyrrolo[2,3-F]pyridine 939 [51] (Scheme 7.14). To avoid formation of the chloro compound 939 a reagent combination of MesSiNCS 937 with triethylamine or DBU, which lacks any competing chloride ion, might give much higher yields of... 

Cations of the type 265, possessing both a thiopyrylium and a dithiole ring, when treated with triethylamine lead to unstable neutral compounds. However, if the reaction is followed by the addition of benzohydroxymoyl chloride [PhC(=NOH)CI], which in situ generates benzonitrile N-oxide, compounds of the type 266 are obtained. A mechanism has been suggested for such transformation [80BSF(2)577]. 

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their N- oxides are prepared from 3-chloropyridazines and their N- oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397>. 

Thiazolo[5,4-(/]pyrimidines are obtained accordingly, starting from 6-chloro-5-nitrouracil with mercaptans and triethylamine. The resulting N-oxide has proved to be an important intermediate for the preparation of several thiazolopyrimidines (81CC278 82JHC77). 

Column Ultrasphere C8 (150x4.6 nm ID), mobile phase acetonitrile - methanol - tetrahydrofuran -0.01 M aqueous triethylamine (pH 2.5 with phosphoric acid)(5 5 3 87), flow rate 1.0 ml/min, fluorescence detection (excitation 245 nm, emission 435 nm). Peaks 1, quinidine-10,11-dihydro-diol 2, 3-hydroxyquinidine 3, quinidine N-oxide 4, quinidine 5, dihydroquinidine 6, 3-me-thyl-5-triazolophtalazine (internal standard) 7, 2 -quinidinone. (Reproduced with permission from ref. 65, by the courtesy of Clinical Chemistry)... 

In more detailed accounts, a range of aromatic and aliphatic nitrile N-oxides, prepared in situ by reaction of the corresponding hydroxamoyl chloride with triethylamine, underwent cycloaddition to 1,3,3-trimethylcylopropene to give 2-oxa-3-azabicyclo[3.1.0]hex-3-enes 2.274,275... 

N-oxide salts (HBTU and TBTU, respectively) [39], or from l-hydroxy-7-azabenzotriazole (HOAt) such as N-[(dimethylamino)-lH-l,2,3-triazolo[4,5-fe] pyridino-l-y]methylene]-N-methy]methanaminium tetrafluoroborate N-oxide (HATU) [40], are well established reagents. They are especially devoted to peptide coupling reactions due to their efficiency and the low degree of undesirable race-mization produced in the final peptide compared to the use of classical carbodi-imide-coupling methods. Therefore, as the polystyrene-supported HOBt is an often used polymeric reagent (Section 7.6.3) [41], its transformation in a supported HOBt and tetramethylurea-derived aminium salt analog to HBTU and TBTU resulted directly. Thus, the reaction of polystyrene-2% divinylbenzene copolymer resin P-HOBt (20) with tetramethylchloroformamidinium tetrafluoroborate (21) (4 equivalents) in the presence of triethylamine gave polymeric N-[(lH-benzotriazol-l-yl)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate N-oxide (P-TBTU, 22) (Scheme 7.6) [42],... 

A convenient synthesis of the triethylamine-sulphur trioxide complex Et3NS03 (129) has been reported by Nair and Bernstein177. A 75% yield of 129 was obtained by the reaction of triethylamine with chlorosulphonic acid. Reaction of quinuclidine N-oxide with SO2 yield a stable colourless, non-hygroscopic material which was identified by X-ray and elemental analysis to be the quinuclidine-sulphur trioxide complex 130178. The complex was exceedingly stable and its hydrolysis in water even at 86 °C was very slow, 280 times slower than the analogous rate for triethylamine-sulphur trioxide (129). A single X-ray structure determination of the complex showed a sulphamic acid type coordination of SO3 to the quinuclidine nucleus [N-S =1.831 (6) A]. 

The transformation shown in equation (27) is inq>ressive since DMSO had pievioasly been tried and shown to fail for this substrate. The reaction was also performed as a one-pot procedure, widi pyridine N-oxide and silver nitrate in acetonitrile followed by addition of triethylamine. This is the preferred method of these authors for these substrates. 

A mixture of phenyl isothiocyanate and diphenylphosphine oxide heated 5 hrs. at 70-80° in the presence of a little triethylamine -> N-phenylthiocarbamyldi-phenylphosphine oxide. Y 15%. F. e. s. I. Ojima, K. Akiba, and N. Inamoto, Bull. Chem. Soc. Japan 42, 2975 (1969). 

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