噻吩-3-乙酸

噻吩-3-乙酸
	IUPAC名; (Thiophen-3-yl)acetic acid
别名	3-TAA; 3-噻吩乙酸
识别
CAS号	6964-21-2
PubChem	23404
ChemSpider	21886
SMILES	C1=CSC=C1CC(=O)O;
性质
化学式	C6H6O2S
摩尔质量	142.18 g·mol⁻¹
外观	无色或白色固体
密度	1.336 g/cm3
熔点	79—80 °C（352—353 K）
pKa	4.39
危险性
GHS提示词	危险
H-术语	H314, H315, H319, H335
P-术语	P260, P261, P264, P271, P280, P301+330+331, P302+352, P303+361+353, P304+340, P305+351+338, P310, P312, P321, P332+313
相关物质
相关化学品	吲哚-3-乙酸; 呋喃-3-乙酸
	若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

噻吩-3-乙酸是一种有机硫化合物，化学式为HO₂CCH₂C₄H₃S，它是白色固体，可用作有机合成的中间体。

合成

噻吩-3-乙酸可由噻吩-3-乙腈的水解得到^[3]，噻吩-3-乙腈则由3-溴噻吩和氰甲基阴离子（⁻CH₂CN）在紫外光下反应得到。^[4]在四(三苯基膦)钯的催化下和氢碘酸的存在下，噻吩-3-乙醇和一氧化碳反应，可以得到噻吩-3-乙酸，副产物是3-甲基噻吩。^[5]若以噻吩-3-甲基溴化镁为原料与二氧化碳反应，生成的主产物则是3-甲基噻吩-2-甲酸。^[6]

反应

噻吩-3-乙酸和N,N'-二环己基碳二亚胺（DCC）在甲苯中反应，可以得到噻吩-3-乙酸酐：^[7]

在硫酸催化下，它在甲醇中回流，可以得到噻吩-3-乙酸甲酯。^[8]

在四氯化锆催化下，它和苄胺在二甲基甲酰胺中反应，可以得到N-苄基噻吩-3-乙酰胺。^[9]它和2-溴苯甲醛（法语：2-Bromobenzaldéhyde）在碳酸钾和钯催化剂的存在下反应，可以得到萘并[1,2-b]噻吩-4-甲酸。^[10]它和氯化亚砜反应，得到噻吩-3-乙酰氯。^[11]

参考文献

^ Campaigne, E.; LeSuer, William M. 3-Substituted Thiophenes. I. Journal of the American Chemical Society (American Chemical Society (ACS)). 1948, 70 (4): 1555–1558. ISSN 0002-7863. doi:10.1021/ja01184a078 （英语）.
^ Demessence, Aude; Rogez, Guillaume; Rabu, Pierre. Grafting of Thiophenecarboxylates into Magnetic Transition Metal Hydroxide Layers. Chemistry of Materials (American Chemical Society (ACS)). 2006, 18 (13): 3005–3015. ISSN 0897-4756. doi:10.1021/cm060366w （英语）.
^ Menghin, Sonja. Analogs of histaprodifen as potent and selective agonists of the histamine H1-receptor. Synthesis, pharmacological characterization, and structure-activity relationships [dissertation]. [Ger. Diss.] D1011-1012, CAN143: 452765. 2004 （德语）.
^ Gol'dfarb, Ya. L.; Yakubov, A. P.; Belen'kii, L. I. Novel synthesis of 3-thienylacetonitrile based on the photostimulated reaction of 3-bromothiophene with cyanomethyl anion. Khimiya Geterotsiklicheskikh Soedinenii. 1979, (8): 1044-1046. ISSN 0453-8234 （俄语）.
^ Lin, Yong-Shou; Yamamoto, Akio. Palladium-catalyzed carbonylation of benzyl alcohol and its analogs promoted by HI in aqueous systems. Tetrahedron Letters (Elsevier BV). 1997, 38 (21): 3747–3750. ISSN 0040-4039. doi:10.1016/s0040-4039(97)00744-2 （英语）.
^ Campaigne, E.; Yokley, O. E. 3-Substituted Thiophenes. XI. Abnormal Products from 3-Thenyl Grignard Reagents1. The Journal of Organic Chemistry (American Chemical Society (ACS)). 1963, 28 (4): 914–917. ISSN 0022-3263. doi:10.1021/jo01039a008 （英语）.
^ Barrios Antúnez, Diego-Javier; Greenhalgh, Mark D.; Brueckner, Alexander C.; Walden, Daniel M.; Elías-Rodríguez, Pilar; Roberts, Patrick; Young, Benjamin G.; West, Thomas H.; Slawin, Alexandra M. Z.; Ha-Yeon Cheong, Paul; Smith, Andrew D. Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2 + 2] cycloaddition: a synthetic and computational study. Chemical Science (Royal Society of Chemistry (RSC)). 2019, 10 (24): 6162–6173. ISSN 2041-6520. doi:10.1039/c9sc00390h （英语）.
^ Brembilla, A.; Collard, A.; Henry, B.; Jadamiec, M.; Lapkowski, M.; Matlengiewicz, M.; Rodehüser, L. Synthesis of Functionalized Thiophenes for the Preparation of Conducting Polymer Films with Complexing Properties. Phosphorus, Sulfur, and Silicon and the Related Elements (Informa UK Limited). 2007-02-15, 182 (4): 723–734. ISSN 1042-6507. doi:10.1080/10426500601047503 （英语）.
^ Lundberg, Helena; Tinnis, Fredrik; Adolfsson, Hans. Direct Amide Coupling of Non-activated Carboxylic Acids and Amines Catalysed by Zirconium(IV) Chloride. Chemistry - A European Journal (Wiley). 2012-02-24, 18 (13): 3822–3826. ISSN 0947-6539. doi:10.1002/chem.201104055 （英语）.
^ Nitti, Andrea; Osw, Peshawa; Calcagno, Giuseppe; Botta, Chiara; Etkind, Samuel I.; Bianchi, Gabriele; Po, Riccardo; Swager, Timothy M.; Pasini, Dario. One-Pot Regiodirected Annulations for the Rapid Synthesis of π-Extended Oligomers. Organic Letters (American Chemical Society (ACS)). 2020-04-07, 22 (8): 3263–3267. ISSN 1523-7060. doi:10.1021/acs.orglett.0c01043 （英语）.
^ Lee-Ruff, E.; Ablenas, Fred J. Acid-catalyzed rearrangement of cyclobutanols. A novel rearrangement. Canadian Journal of Chemistry (Canadian Science Publishing). 1987-07-01, 65 (7): 1663–1667. ISSN 0008-4042. doi:10.1139/v87-278 （英语）.

拓展阅读

Ben Issa, Takoua; Sagaama, Abir; Issaoui, Noureddine. Computational study of 3-thiophene acetic acid: Molecular docking, electronic and intermolecular interactions investigations. Computational Biology and Chemistry (Elsevier BV). 2020, 86: 107268. ISSN 1476-9271. doi:10.1016/j.compbiolchem.2020.107268 （英语）.
Temprado, Manuel; Roux, María Victoria; Jiménez, Pilar; Foces-Foces, Concepción; Notario, Rafael. Thermochemistry of 2- and 3-Thiopheneacetic Acids: Calorimetric and Computational Study. The Journal of Physical Chemistry A (American Chemical Society (ACS)). 2008-09-25, 112 (41): 10378–10385. ISSN 1089-5639. doi:10.1021/jp804672d （英语）.

[1] Campaigne, E.; LeSuer, William M. 3-Substituted Thiophenes. I. Journal of the American Chemical Society (American Chemical Society (ACS)). 1948, 70 (4): 1555–1558. ISSN 0002-7863. doi:10.1021/ja01184a078 （英语）.

[2] Demessence, Aude; Rogez, Guillaume; Rabu, Pierre. Grafting of Thiophenecarboxylates into Magnetic Transition Metal Hydroxide Layers. Chemistry of Materials (American Chemical Society (ACS)). 2006, 18 (13): 3005–3015. ISSN 0897-4756. doi:10.1021/cm060366w （英语）.

[3] Menghin, Sonja. Analogs of histaprodifen as potent and selective agonists of the histamine H1-receptor. Synthesis, pharmacological characterization, and structure-activity relationships [dissertation]. [Ger. Diss.] D1011-1012, CAN143: 452765. 2004 （德语）.

[4] Gol'dfarb, Ya. L.; Yakubov, A. P.; Belen'kii, L. I. Novel synthesis of 3-thienylacetonitrile based on the photostimulated reaction of 3-bromothiophene with cyanomethyl anion. Khimiya Geterotsiklicheskikh Soedinenii. 1979, (8): 1044-1046. ISSN 0453-8234 （俄语）.

[5] Lin, Yong-Shou; Yamamoto, Akio. Palladium-catalyzed carbonylation of benzyl alcohol and its analogs promoted by HI in aqueous systems. Tetrahedron Letters (Elsevier BV). 1997, 38 (21): 3747–3750. ISSN 0040-4039. doi:10.1016/s0040-4039(97)00744-2 （英语）.

[6] Campaigne, E.; Yokley, O. E. 3-Substituted Thiophenes. XI. Abnormal Products from 3-Thenyl Grignard Reagents1. The Journal of Organic Chemistry (American Chemical Society (ACS)). 1963, 28 (4): 914–917. ISSN 0022-3263. doi:10.1021/jo01039a008 （英语）.

[7] Barrios Antúnez, Diego-Javier; Greenhalgh, Mark D.; Brueckner, Alexander C.; Walden, Daniel M.; Elías-Rodríguez, Pilar; Roberts, Patrick; Young, Benjamin G.; West, Thomas H.; Slawin, Alexandra M. Z.; Ha-Yeon Cheong, Paul; Smith, Andrew D. Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2 + 2] cycloaddition: a synthetic and computational study. Chemical Science (Royal Society of Chemistry (RSC)). 2019, 10 (24): 6162–6173. ISSN 2041-6520. doi:10.1039/c9sc00390h （英语）.

[8] Brembilla, A.; Collard, A.; Henry, B.; Jadamiec, M.; Lapkowski, M.; Matlengiewicz, M.; Rodehüser, L. Synthesis of Functionalized Thiophenes for the Preparation of Conducting Polymer Films with Complexing Properties. Phosphorus, Sulfur, and Silicon and the Related Elements (Informa UK Limited). 2007-02-15, 182 (4): 723–734. ISSN 1042-6507. doi:10.1080/10426500601047503 （英语）.

[9] Lundberg, Helena; Tinnis, Fredrik; Adolfsson, Hans. Direct Amide Coupling of Non-activated Carboxylic Acids and Amines Catalysed by Zirconium(IV) Chloride. Chemistry - A European Journal (Wiley). 2012-02-24, 18 (13): 3822–3826. ISSN 0947-6539. doi:10.1002/chem.201104055 （英语）.

[10] Nitti, Andrea; Osw, Peshawa; Calcagno, Giuseppe; Botta, Chiara; Etkind, Samuel I.; Bianchi, Gabriele; Po, Riccardo; Swager, Timothy M.; Pasini, Dario. One-Pot Regiodirected Annulations for the Rapid Synthesis of π-Extended Oligomers. Organic Letters (American Chemical Society (ACS)). 2020-04-07, 22 (8): 3263–3267. ISSN 1523-7060. doi:10.1021/acs.orglett.0c01043 （英语）.

[11] Lee-Ruff, E.; Ablenas, Fred J. Acid-catalyzed rearrangement of cyclobutanols. A novel rearrangement. Canadian Journal of Chemistry (Canadian Science Publishing). 1987-07-01, 65 (7): 1663–1667. ISSN 0008-4042. doi:10.1139/v87-278 （英语）.

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