2-Carboxybenzaldehyde

Typography, demoting focus on synonyms and instead using consistent terminology, conversion from non-idiomatic translation April 2019 September 2017 2-Carboxybenzaldehyd Struktur.svg 150px 2-Formylbenzoic acid 2-Phthaldehydic acid 119-67-5 correct CAS correct FDA OAEGSO7G3Y 8406 204-342-3 17605 234213 8099 742381 1S/C8H6O3/c9-5-6-3-1-2-4-7(6)8(10)11/h1-5H,(H,10,11) DYNFCHNNOHNJFG-UHFFFAOYSA-N C1=CC=C(C(=C1)C=O)C(=O)O C8H6O3 solubleWilliam M. Haynes CRC Handbook of Chemistry and Physics, 97th Edition CRC Press Boca Raton, FL, U.S.A. 3–278 978-1-4987-5429-3 2016 soluble in diethylether, ethanol 2-Carboxybenzaldehyde is a chemical compound. It consists of a benzene ring, with an aldehyde and a carboxylic acid as substituents that are ortho to each other. The compound exhibits ring–chain tautomerism: the two substituents can react with each other to form 3-hydroxyphthalide, a cyclic lactol. This lactol reacts readily with Grignard reagents, forming alkyl- and aryl-substituted phthalides.P. Cannone J. Plamondon M. Akssira Tetrahedron Reactions selectives de organomagnesiens avec les lactols et les lactones. Synthese des diols primaires-secondaires 44 10 2903–2912 1988 10.1016/S0040-4020(88)90027-0 Other benzo-fused heterocyclic compounds can be derived from 2-carboxybenzaldehyde, including isoindolinones and phthalazinones, with a variety of pharmacological properties, such as the antihistamine azelastine. Synthesis 2-Carboxybenzaldehyde was first prepared from phthalide and characterized in 1887.S. Racine Justus Liebigs Ann. Chem. VIII. Ueber Phthalaldehydsäure 239 1 78–91 1887 German 10.1002/jlac.18872390106 https://zenodo.org/record/1427413 The reaction of bromine with phthalide produces 2-bromophthalide, which is converted into 2-formylbenzoic acid by heating with water in a total yield of 78 to 83%.CV3P0737 R.L. Shriner, F.J. Wolf Phthalaldehydic acid 1943 23 74 3 737 10.15227/orgsyn.023.0074 cs2 none 400px|center|Synthese von 2-Carboxybenzaldehyd aus Phthalid An analogous process based on a chlorination reaction can also be used: 250px|center The synthesis of 1-dichloromethyl-2-(trichloromethyl)benzene by photochlorination of o-xylene was also reported in 1887.A. Colson H. Gautier Ann. Chim. Phys. Nouveau mode de chloruration des carbures 6 11 19–32 1887 400px|center|Synthese von 2-Carboxybenzaldehyd aus o-Xylol The hydrolysis of the pentachloroxylene to the 2-carboxybenzaldehyde is carried out by boiling it with FeCl3-containing hydrochloric acid. In the reaction of phthalic anhydride with sodium tetracarbonylferrate, only one of the carboxyl groups is reduced to the aldehyde, the second remains unchanged.Y. Watanabe M. Yamashita T-a. Mitsudo M. Tanaka Y. Takegami Tetrahedron Lett. The facile synthesis of aldehydes and aldehydic acids from carboxylic acid anhydrides using sodium tetracarbonylferrate 14 37 3535–3536 1973 10.1016/S0040-4039(01)86963-X 350px|center|Synthese von 2-Carboxybenzaldehyd aus Phthalsäureanhydrid This gives 2-carboxybenzaldehyde in a yield of 61%. In a laboratory procedure, the oxidation of naphthalene with alkaline potassium permanganate is given, which, however, yields only a yield of 39% 2-carboxybenzaldehyde.CV2P0523 J.H. Gardner, C.A. Naylor, Jr. Phthalaldehydic acid 1936 16 68 2 523 10.15227/orgsyn.016.0068 cs2 none Also the oxidation of naphthalene with ozone to 2-formylbenzoic acid offers no significant advantages.L. Seekles Rec. Trav. Chim. Ortho phthalaldehydic acid 43 5 329–340 1924 10.1002/recl.19240430506 600px|center|Synthese von 2-Carboxybenzaldehyd aus Naphthalin Properties Pure 2-carboxybenzaldehyde is a white crystalline powder which dissolves in water and in short-chain alcohols. In solid form and in most solvents, the substance is present as racemic 3-hydroxyphthalide (a lactol) as a result of ring–chain tautomerism.D.D. Wheeler D.C. Young D.S. Erley J. Org. Chem. Reactions of phthalaldehydic acid 22 5 547–556 1957 10.1021/jo01356a022 300px|center|Gleichgewicht 2-Carboxybenzaldehyd-3-Hydroxyphthalid The refractive index is = 1.4500 (at 25 °C, 589 nm).Carl L. Yaws Thermophysical Properties of Chemicals and Hydrocarbons, 2nd Edition Elsevier Inc. Oxford, UK 183 978-0-323-28659-6 2015 Application In the lactol form, 2-carboxybenzaldehyde behaves like a carboxylic acid anhydride and reacts smoothly with alcohols forming 3-alkoxyphthalides. 300px|center|Reaktion von 3-Hydroxyphthalid mit Nukleophilen Also with other nucleophilic compounds, such as, thiols, amines, amides, etc., 3-hydroxyphthalide reacts without a catalyst to give the corresponding derivatives. For example, it reacts with morpholine in 91% yield to 3-morpholinyl phthalide.K.B. Sloan S.A.M. Koch J. Org. Chem. Effect of Nucleophilicity and Leaving Group Ability on the SN2 Reactions of Amines with (Acyloxy)alkyl α-Halides: A Product Distribution Study 48 5 635–640 1983 10.1021/jo00153a002 3-Hydroxyphthalide reacts with thionyl chloride at the hydroxyl group smoothly (80–90% yield) to 3-chlorophthalide. With Grignard reagents, the hydroxy group can be exchanged for the corresponding alkyl or aryl group: 300px|center|Reaktion von 3-Hydroxyphthalid mit Grignard-Verbindungen In the presence of (+)-cinchonine, in the reaction of (racemic) 3-hydroxyphthalide with carboxylic acid anhydrides to the corresponding chiral 3-substituted phthalides an enantiomeric excess of up to 90% ee can be achieved besides high product yields.D. Niedek S.M.M. Schuler C. Eschmann R.C. Wende A. Seitz F. Keul P.R. Schreiner Synthesis Synthesis of enantioenriched phthalides and isoindolinone derivatives from 2-formylbenzoic acid 49 2 371–382 2017 10.1055/s-0036-1589404 100313676 An alternative approach to (racemic) 3-substituted phthalides with high yields is opened up by the reaction of 2-carboxybenzaldehyde and β-keto acids in the presence of base 4-anisidine in glycerol as solvent.L. Jia F. Han Beilstein J. Org. Chem. Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol 13 1425–1429 2017 10.3762/bjoc.13.139 5530723 28781708 400px|center|Reaktion von 3-Hydroxyphthalid mit β-Ketosäuren 2-Carboxybenzaldehyde undergoes a double condensation reaction with hydrazine or alkylhydrazines, 1(2H)-phthalenazinones are obtained under acid catalysis with K10-montmorillonite and microwave irradiation in high yield.V.M. Outerbridge S.M. Landge H. Tamaki B. Török Synthesis Microwave-promoted solid-acid-catalyzed one-pot synthesis of phthalazinones 2009 1801–1806 2009 11 10.1055/s-0028-1088074 450px|center|Reaktion von 2-Carboxybenzaldehyd mit Alkylhydrazinen Phthalazinones (1(2H)-phthalenazinones) are important building blocks for natural products, fine chemicals and pharmaceutical active ingredients,L. Shi L. Hu J. Wang X. Cao H. Gu Org. Lett. Highly efficient synthesis of N-substituted isoindolinones and phthalazinones using Pt nanowires as catalysts 14 7 1876–1879 2012 10.1021/ol300471a 22420427 such as the antihypertensive vasodilator hydralazine.J. Druey B.H. Ringier Helv. Chim. Acta 21. Hydrazinderivate der Phthalazin- und Pyridazinreihe 34 1 195–210 1951 German 10.1002/hlca.19510340122 2-carboxybenzaldehyde can also be used for the preparation of N-substituted isoindolinones (1-isoindolinones, 2,3-dihydroindol-1-ones) which are formed when reacting 2-carboxybenzaldehyde with primary amines in the presence of platinum nanowires and low hydrogen pressure in 1,4-dioxane in very high yields: 500px|center|Synthese von Isoindolinonen durch 3-Komponentenreaktion When the reaction of 2-carboxybenzaldehyde is carried out with primary amines in the presence of dimethylphosphite, the corresponding isoindolin-1-one-3-phosphonates are obtained first. After activation with butyllithium with aromatic aldehydes (such as, benzaldehyde in a Horner–Wadsworth–Emmons reaction), these can be converted in very high yields to 3-(arylmethylene)isoindolin-1-ones.M.A. Reyes-Gonzàlez A. Zamundio-Medina M. Ordónez Tetrahedron Lett. Practical and highly selective synthesis of 3-(arylmethylene)isoindolin-1-ones from 2-formylbenzoic acid 53 43 5756–5758 2012 10.1016/j.tetlet.2012.08.040 700px|center|Synthese von Arylmethylenisoindolinonen More recently, 2-formylbenzoic acid became due to its reactivity of some interest as versatile molecular building block in multicomponent reactions, for example the Ugi reaction, for the synthesis of heterocyclic annellated aromatics. Functionalized isoindolinones are accessible in high yields in a three-component reaction with 2-formylbenzoic acid and 2-bromoanilines by palladium-catalyzed carbonylation.K. Natte J. Chen H. Li H. Neumann M. Beller X.F. Wu Chem. Eur. J. Palladium-catalyzed carbonylation of 2-bromoanilines with 2-formylbenzoic acid and 2-halobenzaldehydes: Efficient synthesis of functionalized isoindolinones 20 44 14184–14188 2014 10.1002/chem.201404446 25212125 600px|center|Synthese von funktionalisierten Isoindolinonen Another three-component reaction (here carried out as a Strecker synthesis) with 2-carboxybenzaldehyde, primary amines and potassium cyanide in methanol yields in the acidic medium an N-substituted isoindolinone-1-carbonitrile, formally an aminoacetonitrile derivative of isoindolinone with two moles of HCN.T. Opatz D. Ferenc J. Org. Chem. An unexpected three-component condensation leading to amino-(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)-acetonitriles 69 24 8496–8499 2004 10.1021/jo0486802 15549828 600px|center|Synthese von Isoindolinonen aus 2-Carboxybenzaldehyd via Strecker-Synthese When substituted 2-formylbenzoic acid, potassium cyanide and equimolar amounts of primary aromatic amines and acetic acid are used, substituted isochromes-1-ones (isocumarins, 1H-2-benzopyran-1-ones) are obtained in good yields.T. Opatz D. Ferenc Eur. J. Org. Chem. Facile preparation of 3-amino-4-(arylamino)-1H-isochromen-1-ones by a new multi-component reaction 2005 817–821 2005 5 10.1002/ejoc.200400685 600px|center|Synthese von Isochromenonen durch 3-Komponentenreaktion mit Kaliumcyanid The isochromenones obtained are quantitatively converted into isoindolinones by reacting in DMSO upon ring constriction into substituted isobenzofurans or with catalytic amounts of iodine in triethylamine.T. Opatz D. Ferenc Eur. J. Org. Chem. Ring contracting rearrangements of 3-amino-4-(arylamino)-1H-isochromen-1-ones 1 121–126 2006 10.1002/ejoc.200500575 With isonitriles instead of potassium cyanide, 2-carboxybenzaldehyde and primary aromatic amines react in methanol to form substituted isochromen-1-ones, which are converted to isoindolinones with traces of acid.C. Faggi M. Garcia-Valverde S. Macaccini G. Menchi Org. Lett. Isolation of Ugi four-component condensation primary adducts: A straightforward route to isocoumarins 12 4 788–791 2010 10.1021/ol9028622 20104888 600px|center|Synthese von Isochromenonen durch 3-Komponentenreaktion mit Isocyaniden Synthesis pathways for the isoquinoline derivativeJ.W. Wilson N.D. Dawson W. Brooks G.E. Ullyot J. Am. Chem. Soc. Local anesthetics. Aminoalkoxyisoquinoline derivatives 71 3 937–938 1949 10.1021/ja01171a047 18129083 quinisocaineF. v. Bruchhausen etal Hagers Handbuch der Pharmazeutischen Praxis, 5. Aufl. Springer Berlin 482 978-3-642-63389-8 1994 German 10.1007/978-3-642-57880-9 (acting as a local anesthetic) and the antihistamine azelastineG. Scheffler J. Engel B. Kutscher W.S. Sheldrick P. Bell Arch. Pharm. Synthese und Kristallstrukturanalyse von Azelastin 321 4 205–208 1988 German 10.1002/ardp.19883210406 96004319 are also based on 2-carboxybenzaldehyde as starting material. References Category:Benzaldehydes Category:Benzoic acids Category:Aldehydic acids