Synthesis of Primary Amines via Alkylation of the Sodium Salt of Trifluoroacetamide: An Alternative to the Gabriel Synthesis

Harland, Philip A.; Hodge, Philip; Maughan, Wilfrid; Wildsmith, Eric

doi:10.1055/s-1984-31028

Cited by 37 publications

(7 citation statements)

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“…3-(4-Iodobutyloxy)propanenitrile ( 31 ) was obtained by cyanoethylation of 1,4-butanediol, followed by treatment of the resulting nitrile 30 with methyltriphenoxyphosphonium iodide. , Alkylation of 29 with 31 afforded the nitrile 32 . Conversion of the nitrile group in 32 to the amino group using LiAlH 4 and simultaneous removal of the trifluoroacetyl protecting group afforded the diallyl protected polyamine 20 . The di-BOC protected polyamine 19 was prepared from 20 by treatment with di( tert -butyl) dicarbonate followed by cleavage of the allyl groups as described above.…”

Section: Resultsmentioning

confidence: 99%

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

et al. 1999

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Philanthotoxin-433 (PhTX-433), a natural polyamine wasp toxin, is a noncompetitive antagonist of certain ionotropic receptors. Six analogues of PhTX-343 (a synthetic analogue of the natural product), in which the secondary amino groups are systematically replaced by oxygen or methylene groups, have been synthesized by coupling of N-(1-oxobutyl)tyrosine with 1,12-dodecanediamine, 4,9-dioxa-1, 12-dodecanediamine, or appropriately protected di- and triamines, the latter being obtained by multistep syntheses. The resulting PhTX-343 analogues were purified and characterized, and their protolytic properties (stepwise macroscopic pK(a) values) were determined by (13)C NMR titrations. All analogues are fully protonated at physiological pH. The effects of these compounds on acetylcholine-induced currents in TE671 cells clamped at various holding potentials were determined. All of the analogues noncompetitively antagonized the nicotinic acetylcholine receptor (nAChR) in a concentration-, time-, and voltage-dependent manner. The amplitudes of acetylcholine-induced currents were compared at their peaks and at the end of a 1 s application in the presence or absence of the analogues. Most of the analogues were equipotent with or more potent than PhTX-343. The dideaza analogue PhTX-12 [IC(50) of 0.3 microM (final current value)] was the most potent, representing the highest potency improvement (about 50-fold) yet achieved by modification of the parent compound (PhTX-343). Thus, the presence of multiple positive charges in the PhTX-343 molecule is not necessary for antagonism of nAChR. In contrast, the compounds were much less potent than PhTX-343 at locust muscle ionotropic glutamate receptors sensitive to quisqualate (qGluR). The results demonstrate that the selectivity for different types of ionotropic receptors can be achieved by manipulating the polyamine moiety of PhTX-343.

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Section: Resultsmentioning

confidence: 99%

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

et al. 1999

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“…The solution was stirred for 1 h and cooled to -78 °C. A solution of vinylmagnesium bromide in methylene chloride was prepared by three freeze, evaporation, and dilution cycles of the commercially available (Aldrich) 1 M in THF solution of vinylmagnesium bromide. To the aldehyde/magnesium bromide complex was added a 1 M solution of vinylmagnesium bromide in methylene chloride (0.59 mL, 0.59 mmol) slowly via syringe over 15 min.…”

Section: Methyl (S)-4-oxo-3-(phenylmethoxy)butanoate (1) Tomentioning

confidence: 99%

“…(m, 2 ),2.19 (d, J = 6.4 Hz,1 H); 13C NMR (CDC13) 172.4, 138.1, 134.8, 128.7, 128.1,128.1, 117.0, 77.9, 73.2, 72.6, 52.0, 38.2, 36.3; IR (neat) 3480 (br), 3070, 3035, 2955, 2910,1740,1645,1500,1455, 1440.1360.1270.1195.1170.1075.1025, 990, 915, 735, 695; HRMS exact mass caled for (M + 1) C15H2104 265.14203, found 265.14398. Anal.…”

mentioning

confidence: 99%

A useful new enantiomerically pure synthon from malic acid: chelation controlled activation as a route to regioselectivity

Keck¹,

Andrus²,

Romer³

1991

J. Org. Chem.

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“…for electrophilic aromatic substitution reactions [49] or solvolysis studies [50]. Trifluoroacetamide has been used in an alternative procedure to the Gabriel synthesis for amines [51] (Figure 8.5). Conversely, the medium is highly efficient in solvating anions through hydrogen bonding.…”

Section: Trifluoroacetic Acidmentioning

confidence: 99%

Functional Compounds Containing Oxygen, Sulphur or Nitrogen and their Derivatives

Chambers

2004

Fluorine in Organic Chemistry

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This chapter contains only a brief survey of the chemistry of a range of derivatives that are of interest to the organic chemist; further aspects have been discussed in detail and may be referred to elsewhere [1,2]. Because of the extreme electronegativity of fluorine and fluorocarbon groups, the acidities of various functions are increased by introduction of these groups. Some examples are given in Table 8.1: it is clear that fluorocarbon groups have a dramatic effect on the acidities of alcohols and carboxylic acids. Moreover, the CF 3 SO 2 group is one of the most electron-withdrawing groups known [3] and consequently the carbon acid ðCF 3 SO 2 Þ 2 CH 2 is more acidic than trifluoroacetic acid. Also, the sulphonamide ðCF 3 SO 2 Þ 2 NH is a strong acid [4].Conversely, fluorine or fluorocarbon groups have a major effect in reducing the base strength of amines, ethers and carbonyl compounds; for example, 2,2,2-trifluoroethylamine (pK b ¼ 3:3) is ca. 10 5 times less basic than ethylamine. Also, pentafluoropyridine is only protonated in strong acid [6], whereas hexafluoroacetone is not protonated even in superacids [7-9] and perfluorinated tertiary amines and ethers are sufficiently non-basic for them to be used as inert fluids interchangeably with perfluorocarbons.

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Synthesis of Primary Amines via Alkylation of the Sodium Salt of Trifluoroacetamide: An Alternative to the Gabriel Synthesis

Cited by 37 publications

References 0 publications

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

A useful new enantiomerically pure synthon from malic acid: chelation controlled activation as a route to regioselectivity

Functional Compounds Containing Oxygen, Sulphur or Nitrogen and their Derivatives

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