Browse history interactively

Page 1

Page 1Revision 1

Page 2

Page 2Revision 2

← Previous editContent deleted Content addedVisualWikitext

Revision as of 19:12, 26 November 2010 editThe chemistds (talk | contribs)Extended confirmed users5,761 edits Added CSID, Pubchem, (std)InChI, and (std)InChIkey← Previous edit		Latest revision as of 05:24, 23 July 2024 edit undo138.25.88.217 (talk) →Applications of derivativesTags: Mobile edit Mobile web edit
(84 intermediate revisions by 51 users not shown)
Line 1:		Line 1:
			{{Use dmy dates|date=September 2021}}
	{{chembox		{{chembox
	| Watchedfields = changed		|Verifiedfields = changed
			|Watchedfields = changed
	| verifiedrevid = 387430391
			|verifiedrevid = 399005552
	| Name = Isoquinoline
			|Name = Isoquinoline
	| ImageFile = Isoquinoline_chemical_structure.png
			|ImageFile = Isoquinoline numbered.svg
	| ImageSize = 300px
			|ImageSize = 170px
	| ImageName = Chemical structure of Isoquinoline
	| IUPACName = Isoquinoline		|ImageFileL1 = Isoquinoline-3D-balls.png
			|ImageAltL1 = Isoquinoline molecule
	| OtherNames = benzopyridine, 2-benzanine
			|ImageNameL1 = C=black, H=white, N=blue
	| Section1 = {{Chembox Identifiers
			|ImageFileR1 = Isoquinoline-3D-spacefill.png
	| CASNo_Ref = {{cascite}}
			|ImageNameR1 = C=black, H=white, N=blue
	| CASNo = 119-65-3
			|ImageAltR1 = Isoquinoline molecule
	| EINECS = 204-341-8
			|PIN = Isoquinoline<ref name=iupac2013>{{cite book | title = Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = ] | date = 2014 | location = Cambridge | page = 212 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4}}</ref>
	| SMILES = C1(C=NC=C2)=C2C=CC=C1
			|OtherNames = Benzopyridine<br />2-benzazine
	| PubChem = 8405
			|Section1 = {{Chembox Identifiers
	| ChemSpiderID = 8098
			|CASNo_Ref = {{cascite|correct|CAS}}
	| InChI = 1/C9H7N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-7H
			|CASNo = 119-65-3
	| InChIKey = AWJUIBRHMBBTKR-UHFFFAOYAX
			|EINECS = 204-341-8
	| StdInChI = 1S/C9H7N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-7H
			|PubChem = 8405
	| StdInChIKey = AWJUIBRHMBBTKR-UHFFFAOYSA-N
			|ChEMBL_Ref = {{ebicite|changed|EBI}}
	}}
			|ChEMBL = 12315
	| Section2 = {{Chembox Properties
			|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| Formula = C<sub>9</sub>H<sub>7</sub>N
			|ChemSpiderID = 8098
	| MolarMass = 129.16 g/mol
			|DrugBank_Ref = {{drugbankcite|changed|drugbank}}
	| Appearance = yellowish oily liquid, hygroscopic<br />platelets when solid
			|DrugBank = DB04329
	| Density = 1.099 g/cm³
			|UNII_Ref = {{fdacite|changed|FDA}}
	| MeltingPt = 26 - 28 °C
			|UNII = JGX76Y85M6
	| BoilingPtC = 242
			|ChEBI_Ref = {{ebicite|changed|EBI}}
	| pKa=5.14<ref>Brown, H.C., et al., in Baude, E.A. and Nachod, F.C., ''Determination of Organic Structures by Physical Methods'', Academic Press, New York, 1955.</ref>
			|ChEBI = 16092
			|SMILES = C1(C=NC=C2)=C2C=CC=C1
			|InChI = 1/C9H7N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-7H
			|InChIKey = AWJUIBRHMBBTKR-UHFFFAOYAX
			|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			|StdInChI = 1S/C9H7N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-7H
			|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			|StdInChIKey = AWJUIBRHMBBTKR-UHFFFAOYSA-N
			}}
			|Section2 = {{Chembox Properties
			| C = 9 | H = 7 | N = 1
			|Appearance = Colorless oily liquid; hygroscopic platelets when solid
			|Density = 1.099{{nbsp}}g/cm<sup>3</sup>
			|MeltingPtC = 26–28
			|BoilingPtC = 242
			|pKa = pK<sub>BH<sup>+</sup></sub>{{nbsp}}{{=}}{{nbsp}}5.14<ref name=pka>Brown, H.C., et al., in Baude, E.A. and Nachod, F.C., ''Determination of Organic Structures by Physical Methods'', Academic Press, New York, 1955.</ref>
			|MagSus = −83.9·10<sup>−6</sup>{{nbsp}}cm<sup>3</sup>/mol
	}}		}}
	}}		}}
	'''Isoquinoline''' is a ] ] ]. It is a ] of ]. Isoquinoline and quinoline are ]s, which are composed of a ] ring fused to a ] ring. In a broader sense, the term isoquinoline is used to make reference to isoquinoline ]. ] is the structural backbone in naturally occurring ] including ] and ]. The isoquinoline ring in these natural compound derives from the aromatic ] ] <ref>Gilchrist, T.L. (1997). ''Heterocyclic Chemistry'' (3rd ed.). Essex, UK: Addison Wesley Longman.</ref><ref>Harris, J.; Pope, W.J. "''iso''Quinoline and the ''iso''Quinoline-Reds" Journal of the Chemical Society (1922) volume 121, pp. 1029-1033.</ref><ref>Katritsky, A.R.; Pozharskii, A.F. (2000). ''Handbook of Heterocyclic Chemistry'' (2nd ed.). Oxford, UK: Elsevier.</ref><ref>Katritsky, A.R.; Rees, C.W.; Scriven, E.F. (Eds.). (1996). ''Comprehensive Heterocyclic Chemistry II: A Review of the Literature 1982-1995'' (Vol. 5). Tarrytown, NY: Elsevier.</ref><ref>Nagatsu, T. "Isoquinoline neurotoxins in the brain and Parkinson's disease" Neuroscience Research (1997) volume 29, pp. 99-111.</ref><ref>O'Neil, Maryadele J. (Ed.). (2001). ''The Merck Index'' (13th ed.). Whitehouse Station, NJ: Merck.</ref>.		'''Isoquinoline''' is an individual chemical specimen - a ] ] ] - as well as the name of a family of many thousands of natural plant alkaloids, any one of which might be referred to as "an isoquinoline". It is a ] of ]. Isoquinoline and quinoline are ]s, which are composed of a ] ring fused to a ] ring. In a broader sense, the term isoquinoline is used to make reference to isoquinoline ]. ] is the structural backbone in many naturally occurring ] such as ]. The isoquinoline ring in these natural compound derives from the aromatic ] ].<ref>Gilchrist, T.L. (1997). ''Heterocyclic Chemistry'' (3rd ed.). Essex, UK: Addison Wesley Longman.</ref><ref>Harris, J.; Pope, W.J. "''iso''Quinoline and the ''iso''Quinoline-Reds" Journal of the Chemical Society (1922) volume 121, pp. 1029–1033.</ref><ref>Katritsky, A.R.; Pozharskii, A.F. (2000). ''Handbook of Heterocyclic Chemistry'' (2nd ed.). Oxford, UK: Elsevier.</ref><ref>Katritsky, A.R.; Rees, C.W.; Scriven, E.F. (Eds.). (1996). ''Comprehensive Heterocyclic Chemistry II: A Review of the Literature 1982–1995'' (Vol. 5). Tarrytown, NY: Elsevier.</ref><ref>Nagatsu, T. "Isoquinoline neurotoxins in the brain and Parkinson's disease" Neuroscience Research (1997) volume 29, pp. 99–111.</ref><ref>O'Neil, Maryadele J. (Ed.). (2001). ''The Merck Index'' (13th ed.). Whitehouse Station, NJ: Merck.</ref>
	==Properties==		==Properties==
	Isoquinoline is a colorless ] liquid at room temperature with a penetrating, ]. Impure samples can appear brownish, as is typical for nitrogen heterocycles. It crystallizes platelets that have a low ] in ] but dissolve well in ], ], ], ], and other common ]s. It is also soluble in dilute ]s as the protonated derivative.		Isoquinoline is a colorless ] liquid at temperatures above its melting point with a penetrating, ]. Impure samples can appear brownish, as is typical for nitrogen heterocycles. It crystallizes in form of platelets that have a low ] in water but dissolve well in ], ], ], ], and other common ]s. It is also soluble in dilute ]s as the protonated derivative.
	Being an ] of ], isoquinoline is a weak ], with a ] of 8.6. It protonates to form ] upon treatment with ]s, such as HCl. It forms ]s with ]s, such as BF<sub>3</sub>.		Being an ] of pyridine, isoquinoline is a weak ], with a ] of 5.14.<ref name=pka /> It protonates to form ] upon treatment with ]s, such as HCl. It forms ]s with ]s, such as BF<sub>3</sub>.
	==Production==		==Production==
	Isoquinoline was first isolated from ] in 1885 by Hoogewerf and van Dorp. They isolated it by fractional crystallization of the acid sulfate. Weissgerber developed a more rapid route in 1914 by selective extraction of coal tar, exploiting the fact that isoquinoline is more basic than quinoline. Isoquinoline can then be isolated from the mixture by fractional crystallization of the acid sulfate.		Isoquinoline was first isolated from ] in 1885 by Hoogewerf and van Dorp.<ref>S. Hoogewerf and W.A. van Dorp (1885) "Sur un isomére de la quinoléine" (On an isomer of quinoline), ''Recueil des Travaux Chemiques des Pays-Bas'' (Collection of Work in Chemistry in the Netherlands), vol.4, no. 4, pages 125–129. See also: S. Hoogewerf and W.A. van Dorp (1886) "Sur quelques dérivés de l'isoquinoléine" (On some derivatives of isoquinoline), ''Recueil des Travaux Chemiques des Pays-Bas'', vol.5, no. 9, pages 305–312.</ref> They isolated it by ] of the acid sulfate. Weissgerber developed a more rapid route in 1914 by selective extraction of coal tar, exploiting the fact that isoquinoline is more basic than quinoline. Isoquinoline can then be isolated from the mixture by fractional crystallization of the acid sulfate.
	Although isoquinoline derivatives can be synthesized by several methods, relatively few direct methods deliver the unsubstituted isoquinoline. The '''Pomeranz-Fritsch reaction''' provides an efficient method for the preparation of isoquinoline. This reaction uses a ] and aminoacetoaldehyde diethyl acetal, which in an ] ] react to form isoquinoline. Alternatively, ] and a ] ] can be used, to produce the same result.		Although isoquinoline derivatives can be synthesized by several methods, relatively few direct methods deliver the unsubstituted isoquinoline. The ] provides an efficient method for the preparation of isoquinoline. This reaction uses a ] and aminoacetoaldehyde diethyl acetal, which in an ] ] react to form isoquinoline.<ref>{{cite book|last = Li|first = J. J.|title = Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications|chapter = Pomeranz&ndash;Fritz reaction|year = 2014|publisher = ]|isbn = 9783319039794|pages = 490–491|edition = 5th}}</ref> Alternatively, ] and a ] ] can be used, to produce the same result using the Schlittler-Müller modification.<ref>{{cite book|last = Li|first = J. J.|title = Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications|chapter = Schlittler&ndash;Müller modification|year = 2014|publisher = ]|isbn = 9783319039794|pages = 492|edition = 5th|url = https://books.google.com/books?id=HoXBBAAAQBAJ&q=Schlittler-Muller}}</ref>
	]		]
	Several other methods are useful for the preparation of various isoquinoline derivatives.		Several other methods are useful for the preparation of various isoquinoline derivatives.
	In the ] an β-] is acylated and cyclodehydrated by a Lewis acid, such as ] or ]. The resulting 1-substituted-3,4-dihydroisoquinoline can then be dehydrogenated using palladium. The following Bischler-Napieralski reaction produces papaverine.		In the ] an β-phenylethylamine is acylated and cyclodehydrated by a Lewis acid, such as ] or ]. The resulting 1-substituted 3,4-dihydroisoquinoline can then be dehydrogenated using palladium. The following Bischler–Napieralski reaction produces papaverine.
	]
			]
	The '''Pictet-Gams synthesis''' and the ] are both variations on the Bischler-Napieralski reaction. The differences are as follows. The Pictet-Gams reaction avoids the final ] step of the Bischler-Napieralski reaction by constructing a β-] with a hydroxy group in the ]. This reaction results in a 1-alkyl-isoquinoline.
			The ] and the ] are both variations on the Bischler–Napieralski reaction. A Pictet–Gams reaction works similarly to the Bischler–Napieralski reaction; the only difference being that an additional hydroxy group in the reactant provides a site for dehydration under the same reaction conditions as the cyclization to give the isoquinoline rather than requiring a separate reaction to convert a dihydroisoquinoline intermediate.
	]
			]
	The ] combines a β-] and an ] in an ] ], which cyclizes the imine in a reaction of the Mannich type. This produces the ] instead of the ].
			In a Pictet–Spengler reaction, a condensation of a β-] and an ] forms an imine, which undergoes a cyclization to form a ] instead of the ]. In ], the ] ({{EC number|4.2.1.78}}) is an ] that ] a biological Pictect-Spengler synthesis:
			] are ] and ], whereas its two ] are ''(S)''-] and ].]]
			{{clear}}
	Intramolecular aza Wittig reactions also afford isoquinolines.		Intramolecular aza Wittig reactions also afford isoquinolines.
	==Applications of derivatives== <!--debrisoquine redirects here-->		==Applications of derivatives== <!--debrisoquine redirects here-->
	Isoquinolines find many applications, including (but not limited to):		Isoquinolines find many applications, including:
	*anesthetics; ] is one example (shown below).		* anesthetics; ] is one example (shown below).
	]		*: ]
	*antihypertension agents, such as ], ], and ] (all derived from 1,2,3,4-tetrahydroisoquinoline).		* antihypertension agents, such as ] and ] (all derived from 1,2,3,4-tetrahydroisoquinoline).
			* antiretroviral agents, such as ] with an isoquinolyl ], (shown below).
	*antifungal agents, such as 2,2'Hexadecamethylenediisoquinolinium dichloride, which is also used as a topical antiseptic. This derivative, shown below, is prepared by N-alkylation of isoquinoline with the appropriate dihalide.
	]		*: ]
			* vasodilators, a well-known example, ], shown below.
	*disinfectants, like N-laurylisoquinolinium bromide (shown below), which is prepared by simple N-alkylation of isoquinoline.
			*: ]
	]
			* platinum complexes of urea functionalized isoquinolines have been used as anion receptors for chloride and sulfate.<ref>{{Cite journal |last=Bondy |first=Chantelle R. |last2=Gale |first2=Philip A. |last3=Loeb |first3=Stephen J. |date=2004-04-28 |title=Metal−Organic Anion Receptors: Arranging Urea Hydrogen-Bond Donors to Encapsulate Sulfate Ions |url=https://pubs.acs.org/doi/10.1021/ja039712q |journal=Journal of the American Chemical Society |language=en |volume=126 |issue=16 |pages=5030–5031 |doi=10.1021/ja039712q |issn=0002-7863}}</ref>
	*vasodilators, a well-known example, ], shown below.
	]		*: ]
			* Bisbenzylisoquinolinium compounds are compounds similar in structure to ]. They have two isoquinolinium structures, linked by a ] chain, containing two ] linkages.
			==In the human body==
	'''Bisbenzylisoquinolinium''' compounds are compounds similar in structure to ]. They have two isoquinolinium structures, linked by a ] chain, containing two ] linkages.
			], a slowly progressing movement disorder, is thought to be caused by certain ]. A neurotoxin called ] (1-methyl-4-phenyl-1,2,3,6-]), the precursor to MPP<sup>+</sup>, was found and linked to Parkinson's disease in the 1980s. The active neurotoxins destroy ]s, leading to parkinsonism and Parkinson's disease. Several ] derivatives have been found to have the same neurochemical properties as MPTP. These derivatives may act as precursors to active neurotoxins.<ref>{{cite book|doi=10.1007/978-1-4612-2000-8_1|isbn=978-1-4612-7375-2|chapter=Isoquinoline Derivatives|title=Pharmacology of Endogenous Neurotoxins|year=1998|last1=Niwa|first1=Toshimitsu|last2=Kajita|first2=Mitsuharu|last3=Nagatsu|first3=Toshiharu|pages=3–23}}</ref>
	==Isoquinolines and the human body==
	], a slowly progressing movement disorder, is thought to be caused by certain ]. A neurotoxin called ] (1-methyl-4-phenyl-1,2,3,6-]), the precursor to MPP+, was found and linked to Parkinson's disease in the 1980s. The active neurotoxins destroy ]s, leading to parkinsonism and Parkinson's disease. Several ] derivatives have been found to have the same neurochemical properties as MPTP. These derivatives may act as neurotoxin precursors to active neurotoxins.
	==Other uses==		==Other uses==
	Isoquinolines are used in the manufacture of ], ], ] and ]s. It is also used as a ] for the ] of ] and ], and as a ] inhibitor.		Isoquinolines are used in the manufacture of ]s, ]s, ] and ]s. It is also used as a ] for the ] of ]s and ], and as a ] inhibitor.
	==See also==		==See also==
			* ] (1998), an isoquinoline alkaloid
	* ], an analog with the nitrogen atom in position 1.
	* ], an analog without the fused ] ring.		* ], an analog without the nitrogen atom
	* ], an analog without the nitrogen atom.
	* ]s
	==References==		==References==
Line 88:		Line 108:
	==External links==		==External links==
			{{cite EB1911 |wstitle=Quinoline |volume=22 |pages=758–759 |short=1}}
			{{Authority control}}
	{{1911}}
	]		]
			]
			]
	]
	]
	]
	]
	]
	]
	]
	]
	]
	]