四甲基銨鹽

四甲基銨陽離子
	IUPAC名; N,N,N-Trimethylmethanaminium
別名	Tetramethylammonium; Tetramethylazanium; Tetramine
識別
CAS號	51-92-3
PubChem	6380
ChemSpider	6140
SMILES	C[N+](C)(C)C;
InChI	1S/C4H12N/c1-5(2,3)4/h1-4H3/q+1;
InChIKey	QEMXHQIAXOOASZ-UHFFFAOYSA-N
ChEBI	46020
性質
化學式	C4H12N+
摩爾質量	74.14 g·mol⁻¹
危險性（四甲基氯化銨的數據）
	致死量或濃度：
LD50（中位劑量）	25 mg/kg（小鼠，腹腔注射）; 40 mg/kg（小鼠，皮下注射）
LC50（中位濃度）	462 mg/L （96 小時，Pimephales promelas（英語：Pimephales promelas））
相關物質
相關等電子體	新戊烷
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

四甲基銨陽離子，簡稱TMA或Me₄N⁺是最簡單的季銨陽離子，由四個甲基和中心的氮陽離子組成，和新戊烷是等電子體。它有正電荷，只能在平衡離子存在下才能分離。四甲基銨鹽則是這種離子形成的化合物，例如四甲基氯化銨和四甲基氫氧化銨。四甲基銨鹽可用於化學合成，並廣泛用於藥理學研究。

存在

四甲基銨鹽存在於許多海洋生物中，主要是在刺胞動物和軟體動物中，特別是在人類食用的某些香螺屬中。^[4]^[5]它也在非洲的一種植物——Courbonia virgata（英語：Courbonia virgata）中被發現。^[6]

製備、反應、溶液性質

四甲基銨鹽可以由三甲胺和一鹵甲烷直接反應而成：

Me₃N + Me−I → Me₄N⁺I⁻

有¹⁴C 標記的四甲基銨鹽可以通過這種方法製備。^[7]

儘管這個反應對簡單的鹵化物是合適的，不過有更複雜的陰離子的四甲基銨鹽需要使用複分解反應製備。舉個例子，四甲基硼氫化銨可以從四甲基氫氧化銨製備：^[8]

Me₄N⁺[OH]⁻ + Na⁺[BH₄]⁻ → Me₄N⁺[BH₄]⁻ + Na⁺ + HO⁻

類似其它季銨鹽，四甲基銨鹽是一種相轉移催化劑，但由於其高親水性而表現得異常。^[9]

四甲基銨陽離子是親水性的。^[10]

在四甲基銨陽離子中，四個甲基以四面體排列在中心氮原子的周圍，這從其鹽的X射線晶體學研究中就可以明顯看出。^[11]^[12]根據對分子模型的測量，估計四甲基銨陽離子的直徑約為 0.6 nm，^[13]更準確的物理化學測量顯示四甲基銨陽離子的離子半徑為 0.322 nm，也記錄了這種離子的幾個熱力學參數。^[14]^[15]

毒性

四甲基銨鹽的人類毒理學研究主要是在攝入香螺屬後意外中毒的情況下進行的。^[4]四甲基銨鹽中毒症狀包括噁心、嘔吐、頭痛、眩暈/頭暈、視力受損/暫時失明、復視、畏光、缺乏平衡、有中毒感和蕁麻疹。這些症狀會在 30 分鐘內出現，但通常會在幾個小時後完全恢復。只有一個人在攝入來自Courbonia virgata的四甲基銨鹽後死亡的記錄。^[6]雖然這些症狀中大多可以根據自主神經系統中的神經傳遞受損來解釋，但似乎也有明顯的中樞影響跡象。^[4]

在動物研究中，將含有四甲基銨鹽的香螺屬提取物對小鼠、貓和魚進行腸胃外給藥，主要表現出涉及骨骼肌的影響：肌肉震顫、抽搐、失去平衡、運動麻痹，最終呼吸停止。^[4]

四甲基銨鹽對人類的致死量估計為 3–4 mg/kg（口服），^[4]^[6]對大鼠的致死量則估計為 ~45–50 mg/kg（口服）和 ~15 mg/kg（腹腔注射）^[16]

參見

四乙基銨鹽

參考資料

^ ^1.0 ^1.1 Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014: 1086. ISBN 978-0-85404-182-4. doi:10.1039/9781849733069-FP001.
^ R. J. Lewis (Ed.) (2004), Sax's Dangerous Properties of Industrial Materials, 11th Ed. p. 3409, Wiley-Interscience, Wiley & Sons, Inc., Hoboken, NJ.
^ http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+7987
^ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 Anthoni, U.; Bohlin, L.; Larsen, C.; Nielsen, P.; Nielsen, N. H.; Christophersen, C. Tetramine: Occurrence in marine organisms and pharmacology. Toxicon. 1989, 27: 707–716. doi:10.1016/0041-0101(89)90037-8.
^ Dolan, L. C.; Matulka, R. A.; Burdock, G. A. Naturally occurring food toxins. Toxins (Basel). 2010, 2: 2289–2332. PMC 3153292 . PMID 22069686. doi:10.3390/toxins2092289.
^ ^6.0 ^6.1 ^6.2 Henry, A. J. The toxic principle of Courbonia virgata: its isolation and identification as a tetramethylammonium salt. Br. J. Pharmacol. Chemother. 1948, 3: 187–188. PMC 1509833 . PMID 18883998. doi:10.1111/j.1476-5381.1948.tb00373.x.
^ Tsubaki, H.; Nakajima, E.; Komai, T.; Shindo, H. The relation between structure and distribution of quaternary ammonium ions in mice and rats. Simple tetraalkylammonium and a series of m-substituted trimethylphenylammonium ions. J. Pharmacobio-Dyn. 1986, 9: 737–746. doi:10.1248/bpb1978.9.737 .
^ Banus, M. D.; Bragdon, R. W.; Gibb, T. R. P. Preparation of quaternary ammonium borohydrides from sodium and lithium borohydrides. J. Am. Chem. Soc. 1952, 74: 2346–2348. doi:10.1021/ja01129a048.
^ Fedorynski, M.; Ziolkowska, W.; Jonczyk, A. Tetramethylammonium salts: highly selective catalysts for the preparation of gem-dichlorocyclopropanes from electrophilic alkenes and chloroform under phase-transfer catalysis conditions. J. Org. Chem. 1993, 58: 6120–6121. doi:10.1021/jo00074a047.
^ Koga, Y.; Westh, P.; Nishikawa, K.; Subramanian, S. Is a methyl group always hydrophobic? Hydrophilicity of trimethylamine-N-oxide, tetramethyl urea and tetramethylammonium ion. J. Phys. Chem. B. 2011, 115: 2995–3002. doi:10.1021/jp108347b.
^ McLean, W. J.; Jeffrey, G. A. Crystal structure of tetramethylammonium fluoride tetrahydrate. J. Chem. Phys. 1967, 47: 414–417. doi:10.1063/1.1711910.
^ McCullough, J. D. The crystal structure of tetramethylammonium perchlorate. Acta Crystallogr. 1964, 17: 1067–1070. doi:10.1107/s0365110x64002687 .
^ McCleskey, E. W.; Almers, W. The Ca channel in skeletal muscle is a large pore. Proc. Natl. Acad. Sci. USA. 1985, 82: 7149–7153. PMC 391328 . PMID 2413461. doi:10.1073/pnas.82.20.7149.
^ Aue, D. H.; Webb, H. M.; Bowers, M. T. A thermodynamic analysis of solvation effects on the basicities of alkylamines. An electrostatic analysis of substituent effects. J. Am. Chem. Soc. 1976, 98: 318–329. doi:10.1021/ja00418a002.
^ Palomo, J.; Pintauro, P. N. Competitive absorption of quaternary ammonium and alkali metal cations into a Nafion cation-exchange membrane. J. Membrane Sci. 2003, 215: 103–114. doi:10.1016/s0376-7388(02)00606-3.
^ Anthoni, U.; Bohlin, L.; Larsen, C.; Nielsen, P.; Nielsen, N. H.; Christophersen, C. The toxin tetramine from the "edible" whelk Neptunea antiqua. Toxicon. 1989, 27: 717–723. doi:10.1016/0041-0101(89)90038-x.

[iupac2013-1] 1.0 ^1.1 Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014: 1086. ISBN 978-0-85404-182-4. doi:10.1039/9781849733069-FP001.

[2] R. J. Lewis (Ed.) (2004), Sax's Dangerous Properties of Industrial Materials, 11th Ed. p. 3409, Wiley-Interscience, Wiley & Sons, Inc., Hoboken, NJ.

[3] ttp://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+7987

[Ant-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 Anthoni, U.; Bohlin, L.; Larsen, C.; Nielsen, P.; Nielsen, N. H.; Christophersen, C. Tetramine: Occurrence in marine organisms and pharmacology. Toxicon. 1989, 27: 707–716. doi:10.1016/0041-0101(89)90037-8.

[5] Dolan, L. C.; Matulka, R. A.; Burdock, G. A. Naturally occurring food toxins. Toxins (Basel). 2010, 2: 2289–2332. PMC 3153292 . PMID 22069686. doi:10.3390/toxins2092289.

[Hen-6] 6.0 ^6.1 ^6.2 Henry, A. J. The toxic principle of Courbonia virgata: its isolation and identification as a tetramethylammonium salt. Br. J. Pharmacol. Chemother. 1948, 3: 187–188. PMC 1509833 . PMID 18883998. doi:10.1111/j.1476-5381.1948.tb00373.x.

[Tsu-7] Tsubaki, H.; Nakajima, E.; Komai, T.; Shindo, H. The relation between structure and distribution of quaternary ammonium ions in mice and rats. Simple tetraalkylammonium and a series of m-substituted trimethylphenylammonium ions. J. Pharmacobio-Dyn. 1986, 9: 737–746. doi:10.1248/bpb1978.9.737 .

[8] Banus, M. D.; Bragdon, R. W.; Gibb, T. R. P. Preparation of quaternary ammonium borohydrides from sodium and lithium borohydrides. J. Am. Chem. Soc. 1952, 74: 2346–2348. doi:10.1021/ja01129a048.

[9] Fedorynski, M.; Ziolkowska, W.; Jonczyk, A. Tetramethylammonium salts: highly selective catalysts for the preparation of gem-dichlorocyclopropanes from electrophilic alkenes and chloroform under phase-transfer catalysis conditions. J. Org. Chem. 1993, 58: 6120–6121. doi:10.1021/jo00074a047.

[10] Koga, Y.; Westh, P.; Nishikawa, K.; Subramanian, S. Is a methyl group always hydrophobic? Hydrophilicity of trimethylamine-N-oxide, tetramethyl urea and tetramethylammonium ion. J. Phys. Chem. B. 2011, 115: 2995–3002. doi:10.1021/jp108347b.

[11] McLean, W. J.; Jeffrey, G. A. Crystal structure of tetramethylammonium fluoride tetrahydrate. J. Chem. Phys. 1967, 47: 414–417. doi:10.1063/1.1711910.

[12] McCullough, J. D. The crystal structure of tetramethylammonium perchlorate. Acta Crystallogr. 1964, 17: 1067–1070. doi:10.1107/s0365110x64002687 .

[13] McCleskey, E. W.; Almers, W. The Ca channel in skeletal muscle is a large pore. Proc. Natl. Acad. Sci. USA. 1985, 82: 7149–7153. PMC 391328 . PMID 2413461. doi:10.1073/pnas.82.20.7149.

[Aue-14] Aue, D. H.; Webb, H. M.; Bowers, M. T. A thermodynamic analysis of solvation effects on the basicities of alkylamines. An electrostatic analysis of substituent effects. J. Am. Chem. Soc. 1976, 98: 318–329. doi:10.1021/ja00418a002.

[15] Palomo, J.; Pintauro, P. N. Competitive absorption of quaternary ammonium and alkali metal cations into a Nafion cation-exchange membrane. J. Membrane Sci. 2003, 215: 103–114. doi:10.1016/s0376-7388(02)00606-3.

[16] Anthoni, U.; Bohlin, L.; Larsen, C.; Nielsen, P.; Nielsen, N. H.; Christophersen, C. The toxin tetramine from the "edible" whelk Neptunea antiqua. Toxicon. 1989, 27: 717–723. doi:10.1016/0041-0101(89)90038-x.

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