610-99-1

Basic information

• Product Name: 2'-Hydroxypropiophenone
• Synonyms: 2-HYDROXYPHENYL ETHYL KETONE;2'-HYDROXYPROPIOPHENONE;2-HYDROXYPROPIOPHENONE;O-HYDROXYPROPIOPHENONE;2-HYDROXYNITROBENZENE;2''-HYDROXYACETOPHENONEPROPAFENONE;2''-HYDROXYPROPRIOPHENONE;o-Hydroxylpropiophenone
• CAS NO: 610-99-1
• Molecular Formula: C₉H₁₀O₂
• Molecular Weight: 150.17
• EINECS: 210-244-1
• Product Categories: Aromatic Propiophenones (substituted);Building Blocks;C9;Carbonyl Compounds;Chemical Synthesis;Ketones;Organic Building Blocks
• Mol File: 610-99-1.mol

Chemical Properties

• Melting Point: 20-22 °C
• Boiling Point: 115 °C15 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Clear brownish liquid
• Density: 1.094 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.548(lit.)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 8.33±0.35(Predicted)
• BRN: 1860264
• CAS DataBase Reference: 2'-Hydroxypropiophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 2'-Hydroxypropiophenone(610-99-1)
• EPA Substance Registry System: 2'-Hydroxypropiophenone(610-99-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 610-99-1(Hazardous Substances Data)

Usage

Preparation

Obtained by Fries rearrangement of phenyl propionatewith aluminium chloride in refluxing carbon disulfide ?, then at 130–150° for 2–3 h after solvent elimination (32–35%)with aluminium chloride in chlorobenzene using microwave irradiation for 3 ? min at 106° (28%) with aluminium chloride in nitrobenzene at 50° for 18 h (16%) or at ? 20° for 48 h (10%) with aluminium chloride in nitromethane at 20° for 7 days (20%) with aluminium chloride in heptane at 80–90° for 7 h (53%) or in tetrachlo-? roethane at 95° for 5 h (43%) with aluminium chloride without solvent at 250° for 5 min or at 180–200° for ? 15 min (76–78%), at 140–160° (32–35%), at 140°with zirconium chloride in o-dichlorobenzene at 120° for 3 h (83%) with titanium tetrachloride in o-dichlorobenzene at 150° for 1 h (62%) ?, in nitromethane at 20° for 7 days (13%) or without solvent at 50° for 10 h (30%)with titanium tetrabromide in o-dichlorobenzene at 150° for 1 h (60%) with stannic chloride at 50° for 3 h (25%) with boron trifluoride at 120–135° for 15 min (15%) with zinc chloride at 180–200° for 15 min (10%) with polyphosphoric acid at 100° (13%) Also obtained by Friedel–Crafts acylation of phenol with propionyl chloride in the presence of aluminium chloride (40%), at 120–130° for 1 h (45%) according to the method Also obtained by acylation of phenol with propionic acidin the presence of boron trifluoride at 165° for 1 h (45%) or at 80° for ? 2 h (8%) in the presence of polyphosphoric acid at 100° for 10 min (by-product) in the presence of zinc chloride at 160° for 1 h Also obtained by isomerization of 4-hydroxypropiophenone with aluminium chloride (1.5 equiv) at 165° for 1 h (40%) or at 180–200° for 15 min (55%) Also obtained by demethylation of 2-propionylanisole with fuming hydrochloric acid (d = 1.19) in a sealed tube at 110° for 6 h Also obtained (by-product) by heating 3-tert-butyl-4-hydroxypropiophenone with aluminium chloride at 170° for 15 min (13%) Also obtained by treatment of 2,3-dimethylchromone with sodium ethoxide in boiling ethanol for 30 h according to the method Also obtained from 2-allylphenol by treatment with perbenzoic acid in ethyl ether, first at 0°, then between 0° and 25° for 24 h (78%) Also obtained by reaction of 2-bromophenyl propionate in a ethyl ether/hexane/THF mixture at low temperature (?78 to ?95°) with sec-butyllithium to give, after hydrolysis, the titled ketone (metal-promoted Fries rearrangement) (17%) Also obtained by reaction of ethylmagnesium bromidewith 2-hydroxybenzamide in boiling benzene, followed by hydrolysis ? (30%)with 2-hydroxy-N,N-diethylbenzamide in boiling benzene, followed by ? hydrolysis (82–84%) Also isolated by heating of 1-(o-hydroxyphenyl)cyclopropyltrimethylam-monium iodide for 1 h at 140° with 1.5 equiv of N,N-diisopropylethylamine (not water-free) (38%) Also obtained by hydrolysis of 2-(1-methyliminopropyl)phenol (4aa) with aqueous acetic acid/THF at 40° for 4 h (86%)Also obtained by photolysis of phenyl propionate in water or in solution containing b-cyclodextrine (254 nm) at 25° for 2 h Also obtained by treatment of 2-(1-hydroxypropyl)phenol with MnO2 in methylene chloride for 7 h at r.t.

Upstream product

• 79-03-8 propionyl chloride 
• 108-95-2 phenol 
• 121-45-9 phosphorous acid trimethyl ester 
• 637-27-4 phenyl propionate 
• 74-96-4 ethyl bromide 
• 611-20-1 salicylonitrile 
• 74-85-1 ethene 
• 69-72-7 salicylic acid 
• 802294-64-0 propionic acid 
• 88284-48-4 2-(trimethylsilyl)phenyl trifluoromethanesulfonate 
• 994-30-9 triethylsilyl chloride 
• 19311-91-2 N,N-diethylsalicylamide 
• 65009-00-9 O-phenyl N,N-diethylcarbamate 
• 69730-61-6 C₁₁H₉F₃O₃ 

Downstream Products

• 64686-65-3 2'-benzyloxypropiophenone 
• 19728-14-4 2-(2-propanoylphenoxy)acetic acid 
• 20924-63-4 ethyl 3-methyl-4-oxo-4H-chromene-2-carboxylate 
• 31826-78-5 2-propionylphenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 
• 154050-14-3 2-cyanato-propiophenone 
• 56481-70-0 2,4-dipropionylphenol 
• 36039-26-6 5-acetyl-2-hydroxypropiophenone 
• 142819-88-3 1-(2-isopropoxyphenyl)propan-1-one 
• 107075-29-6 1-(2-Hydroxy-phenyl)-2-methyl-3-pyrrolidin-1-yl-propan-1-one 
• 211801-15-9 (Z)-4,4,5,5,6,6,6-Heptafluoro-3-(2-propionyl-phenoxy)-hex-2-enoic acid ethyl ester 
• 929341-33-3 1-(2-difluoromethoxy-phenyl)-propan-1-one 
• 644-35-9 5-propylphenol 
• 1481-84-1 2-hydroxy-α-ethylbenzylalcohol 
• 71972-66-2 3-methyl-2-phenyl-4H-1-benzopyran-4-one 

Relevant articles and documents

Relay Catalysis by Achiral Borane and Chiral Phosphoric Acid in the Metal-Free Asymmetric Hydrogenation of Chromones

A strategy of relay catalysis by achiral borane and chiral phosphoric acid was successfully developed for the asymmetric hydrogenation of chromones, giving the desired products in high yields with up to 95% ee. Achiral borane and chiral phosphoric acid are highly compatible in this reaction. The achiral borane acts as a Lewis acid for the first-step hydrogenation, and the chiral phosphoric acid acts as an effective chiral proton shuttle to control the enantioselectivity.

Photoredox/nickel-catalyzed hydroacylation of ethylene with aromatic acids

We report a general, practical and scalable hydroacylation reaction of ethylene with aromatic carboxylic acids with the synergistic combination of nickel and photoredox catalysis. Under ambient temperature and pressure, feedstock chemicals such as ethylene can be converted into high-value-added aromatic ketones in moderate to good yields (up to 92%) with reaction time of 2-6 hours.

Rhoda-Electrocatalyzed Bimetallic C?H Oxygenation by Weak O-Coordination

Rhodium-electrocatalyzed arene C?H oxygenation by weakly O-coordinating amides and ketones have been established by bimetallic electrocatalysis. Likewise, diverse dihydrooxazinones were selectively accessed by the judicious choice of current, enabling twofold C?H functionalization. Detailed mechanistic studies by experiment, mass spectroscopy and cyclovoltammetric analysis provided support for an unprecedented electrooxidation-induced C?H activation by a bimetallic rhodium catalysis manifold.

C?H Oxygenation Reactions Enabled by Dual Catalysis with Electrogenerated Hypervalent Iodine Species and Ruthenium Complexes

The catalytic generation of hypervalent iodine(III) reagents by anodic electrooxidation was orchestrated towards an unprecedented electrocatalytic C?H oxygenation of weakly coordinating aromatic amides and ketones. Thus, catalytic quantities of iodoarenes in concert with catalytic amounts of ruthenium(II) complexes set the stage for versatile C?H activations with ample scope and high functional group tolerance. Detailed mechanistic studies by experiment and computation substantiate the role of the iodoarene as the electrochemically relevant species towards C?H oxygenations with electricity as a sustainable oxidant and molecular hydrogen as the sole by-product. para-Selective C?H oxygenations likewise proved viable in the absence of directing groups.

The insertion of arynes into the O-H bond of aliphatic carboxylic acids

The insertion of arynes into the O-H bond of aliphatic carboxylic acids promoted by sodium carboxylates is described. The reactions led to the formation of aryl carboxylates in good yields with good chemoselectivities under mild conditions.

Lithiation of a silyl ether: Formation of an ortho-fries hydroxyketone

A hydroxy-directed alkylation of an N,N-diethylarylamide using CIPE-assisted α-silyl carbanions (CIPE=complex-induced proximity effect) has been developed using a simple reagent combination of LDA (lithium diisopropylamide) and chlorosilane. A study of the mechanism, and the application of the procedure to an anionic Snieckus-Fries rearrangement for a highly efficient synthesis of the potent phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, are reported.

Broadening the catalyst and reaction scope of regio- and chemoselective C-H oxygenation: A convenient and scalable approach to 2-acylphenols by intriguing Rh(ii) and Ru(ii) catalysis

A unique Rh(ii) and Ru(ii) catalyzed C-H oxygenation of aryl ketones and other arenes has been developed for the facile synthesis of diverse functionalized phenols. The reaction demonstrates excellent reactivity, regio- and chemoselectivity, good functional group compatibility and high yields. The practicality of this method has been proved by gram-scale synthesis of a few different 2-acylphenols. Its utility has been well exemplified in further applications in heterocycle synthesis and direct modifications of drug Fenofibrate.

Synthesis of ortho-acylphenols through the palladium-catalyzed ketone-directed hydroxylation of arenes

ortho-Acylphenols are an important structural motif found in a diversity of bioactive molecules ranging from natural products to drugs (Figure 1). Moreover, they also serve as versatile building blocks for the synthesis of various pharmaceuticals, such as warfarin, as well as agrichemicals, flavors, and fragrances. Classic approaches to the synthesis of o-acylphenols generally involve a two-step process: acylation of phenols followed by Fries rearrangement of the resulting phenyl esters (Scheme 1a). On the other hand, direct C-acylation of phenols has also been known under more forcing conditions. Although effective, these approaches are often complicated by the formation of undesired p-substituted products when bulky acyl groups need to be introduced, as well as the limited variety of ketones that can be generated.

Pd-catalyzed C-H oxygenation with TFA/TFAA: Expedient access to oxygen-containing heterocycles and late-stage drug modification

Functionalized phenols are valuable industrial chemicals related to pharmaceuticals, agrochemicals, and polymers. Therefore, the direct catalytic hydroxylation of arenes to produce phenols has attracted much attention. Although tremendous progress has been made in this field, there are still difficult substrates which remain unmet challenges for direct hydroxylation in terms of regio- and chemoselectivity, as well as the practicality of current methods (Scheme 1). For example, 2-hydroxy aromatic ketones are useful synthetic intermediates for the preparation of various oxygen-containing heterocycles such as benzofuranone, chromanone, benzoxazole, and dibenzooxazepine; they also serve as key building blocks for drugs such as celiprolol, acebutolol, and propafenone. Traditional strategies for accessing 2-hydroxy aromatic ketones have mainly involved the oxidation of benzylic alcohols, the hydrolysis of aromatic halides, Fries rearrangement of esters or the demethylation of methyl phenyl ether. These methods generally suffer from one limitation or another, such as tedious reaction procedures, harsh reaction conditions, low yields, or the formation of side products. Hence, direct transformation of readily available aromatic ketones into valuable 2-hydroxylated products by transition metal-catalyzed C-H functionalization is arguably a highly efficient and atom-economic method to access these compounds. Moreover, developing a more general strategy for the regio- and chemoselective C-H oxygenation of a variety of challenging arenes would be especially desirable for phenol synthesis (Scheme 1).

Low-energy collision-induced fragmentation of negative ions derived from ortho-, meta-, and para-hydroxyphenyl carbaldehydes, ketones, and related compounds

Collision-induced dissociation (CID) mass spectra of anions derived from several hydroxyphenyl carbaldehydes and ketones were recorded and mechanistically rationalized. For example, the spectrum of m/z 121 ion of deprotonated ortho-hydroxybenzaldehyde shows an intense peak at m/z 93 for a loss of carbon monoxide attributable to an ortho-effect mediated by a charge-directed heterolytic fragmentation mechanism. In contrast, the m/z 121 ion derived from meta and para isomers undergoes a charge-remote homolytic cleavage to eliminate an ?H and form a distonic anion radical, which eventually loses CO to produce a peak at m/z 92. In fact, for the para isomer, this two-step homolytic mechanism is the most dominant fragmentation pathway. The spectrum of the meta isomer on the other hand, shows two predominant peaks at m/z 92 and 93 representing both homolytic and heterolytic fragmentations, respectively. 18O-isotope-labeling studies confirmed that the oxygen in the CO molecule that is eliminated from the anion of meta-hydroxybenzaldehyde originates from either the aldehydic or the phenolic group. In contrast, anions of ortho-hydroxybenzaldehyde and 2-hydroxy-1-naphthaldehyde, both of which show two consecutive CO eliminations, specifically lose the carbonyl oxygen first, followed by that of the phenolic group. Anions from 2-hydroxyphenyl alkyl ketones lose a ketene by a hydrogen transfer predominantly from the α position. Interestingly, a very significant charge-remote 1,4-elimination of a H2 molecule was observed from the anion derived from 2,4-dihydroxybenzaldehyde. For this mechanism to operate, a labile hydrogen atom should be available on the hydroxyl group adjacent to the carbaldehyde functionality. Copyright