Cyclobutanol
Cyclobutanol
CAS: 2919-23-5
Molecular Formula: C4H8O
Cyclobutanol - Names and Identifiers
| Name | Cyclobutanol |
| Synonyms | CYCLOBUTANOL Cyclobutanol 1-Cyclobutanol Cyclobutane-1-ol HYDROXYCYCLOBUTANE Cyclobutyl alcohol Cyclobutyl hydroxide |
| CAS | 2919-23-5 |
| EINECS | 220-858-1 |
| InChI | InChI=1/C4H8O/c5-4-2-1-3-4/h4-5H,1-3H2 |
| InChIKey | KTHXBEHDVMTNOH-UHFFFAOYSA-N |
Cyclobutanol - Physico-chemical Properties
| Molecular Formula | C4H8O |
| Molar Mass | 72.11 |
| Density | 0.921 g/mL at 25 °C (lit.) |
| Melting Point | 262-263 °C |
| Boling Point | 123 °C/733 mmHg (lit.) |
| Flash Point | 70°F |
| Solubility | Partly soluble. |
| Vapor Presure | 6.1mmHg at 25°C |
| Appearance | Liquid |
| Color | Clear colorless |
| BRN | 2035937 |
| pKa | 15.31±0.20(Predicted) |
| Storage Condition | Sealed in dry,2-8°C |
| Refractive Index | n20/D 1.435(lit.) |
Cyclobutanol - Risk and Safety
| Risk Codes | 10 - Flammable |
| Safety Description | S23 - Do not breathe vapour. S24/25 - Avoid contact with skin and eyes. S16 - Keep away from sources of ignition. |
| UN IDs | UN 1987 3/PG 2 |
| WGK Germany | 3 |
| TSCA | Yes |
| HS Code | 29061990 |
| Hazard Class | 3 |
| Packing Group | II |
Cyclobutanol - Reference Information
| NIST chemical information | Information provided by: webbook.nist.gov (external link) |
| EPA chemical information | Information provided by: ofmpub.epa.gov (external link) |
| Overview | There are two orientations of hydroxyl groups in cyclobutanol, namely the equatorial direction or the axial direction, which adds a new degree of freedom and can form four molecular conformations, namely equatorial-trans (Eq-t, equatorial-trans), equatorial-intertorsional (Eq-g, equatorial-gauche), axial-trans (Ax-t, axial-trans) and axial-intertorsional (Ax-t, axial-trans-gauche). In recent years, as a synthetic precursor, cyclobutanol has been successfully applied to the regioselective synthesis of γ-substituted fatty ketones. Among them, the C- C bond is broken mainly through the β-carbon elimination reaction of transition metal alkoxide and the participation of free radicals in the oxidative ring-opening reaction. Compared with conventional methods, cyclobutanol raw materials are prepared by Grignard reaction, and the source is cheap and easy to obtain; secondly, by reacting with different coupling reagents, the diverse synthesis of γ-substituted fatty ketones can be achieved. |
| Ring-opening reaction | Cyclobutanol ring-opening functionalization reaction is one of the important strategies for preparing γ-substituted fatty ketones. Through the construction of regioselective C- C bond cleavage and new chemical bonds (e. g. C- C, C- N, C- O, C- F bond, etc.), the ring-opening reaction of cyclobutanol can efficiently introduce various substituents at the γ position of the carbonyl group. The ring-opening reaction pathways of cyclobutanol are mainly divided into two types: 1. Ring-opening through the β-carbon elimination reaction catalyzed by transition metal palladium and rhodium; 2. Ring-opening through single electron oxidation of cyclobutanol with free radical history. Palladium-catalyzed ring-opening reaction of cyclobutanol In 1999, the Uemura team reported that under oxygen conditions, Pd (II) catalyzed ring-opening reaction of cyclobutanol to prepare β,γ-unsaturated ketones. In this reaction, they speculated that the cyclobutanol palladium (Ⅱ) salt may be formed first, and then the intermediate can easily undergo β-carbon elimination on the side with less resistance, thereby breaking the C- C bond to form alkyl palladium (Ⅱ) intermediates, and finally undergo β-hydrogen elimination to obtain olefin products. The following figure: In the above reaction conditions, oxygen is required as an oxidant, indicating that the reaction is a catalytic cycle of Pd(Ⅱ)/Pd(0) species. On the other hand, the catalytic cycle of Pd(0)/Pd (II) also often occurs in palladium catalytic reactions involving halogenated aromatics. Inspired by the above reaction, they used Pd(0) as a catalyst to catalyze the reaction of cyclobutanol and halogenated aromatic hydrocarbons, realized the four-membered ring-opening arylation, and constructed γ-aryl fatty ketone. During the reaction, Pd(0) and the Pd (II) intermediate formed in situ from halogenated aromatics react with cyclobutanol to form palladium, followed by β-carbon elimination and reduction elimination reactions to obtain arylation products. The transformation has high reaction yield and good substrate compatibility. See the following figure: the ring-opening reaction of free radical process cyclobutanol oxidation ring-opening construction, carbon-carbon bond-four-membered ring in which free radicals participate, ring-opening is usually used as a "free radical clock" reaction in free radical-related kinetic research. Using the principle of "free radical clock", cyclobutanol is used as the precursor to undergo a ring-opening reaction involving free radicals, and various functionalization reactions of carbonyl γ can be realized. Rocek found that Ce(Ⅳ) of ceric ammonium nitrate can oxidize cyclobutanol to open the ring. Based on this study, in 1993, the Kapustina team developed a Minisci reaction involving cyclobutanol and prepared a series of fatty ketones substituted by γ-azaaryl ring. When acetic acid is used as solvent and equivalent Pb(OAc)4 or Mn(OAc)3 is used as oxidant, cyclobutanol is oxidized to generate cyclobutyl oxygen radical, which isomerizes to open the ring to generate γ-carbonyl alkyl radical. Alkyl radicals are added to the protonated electricity-deficient heterocycle to obtain the product of γ-azaaryl ring substitution. When the heterocyclic ring is pyridine, the ortho position of the nitrogen atom is the main reaction site, and the ratio of the ortho product to the para product is about 3:1; and when the heterocyclic ring is quinoline, the reaction selectivity is poor, and the ortho The ratio of the product to the para product is about 1:1. Later, they developed the reaction to solid-phase catalysis, which was more efficient. |
| Use | manganese-catalyzed cyclobutanol ring-opening to construct γ-azide aliphatic ketones. Alkyl azide is a very important synthetic intermediate. It is widely used in the chemical synthesis of nitrogen-containing compounds. In addition, due to the mild conversion conditions, the biocompatible reaction involving alkyl azide is also widely used in chemical biology research. Using cheap manganese acetate as catalyst, TMSN3 as azide source, high iodide BI-OH as oxidant, cyclobutanol can open the ring to obtain γ-azide products. The reaction conditions are mild, the functional group compatibility is wide, and the first, second and third aliphatic azides can be obtained regioselectively. In addition, under this reaction condition, cyclobutanol with a ring skeleton can undergo an expanded azide reaction to obtain a series of azide-substituted benzocyclone products that are difficult to synthesize by other methods. Preliminary mechanism studies believe that the reaction is achieved through the catalytic cycle of MnIII/MnV with the participation of free radicals. |
| There is a problem | With the aid of the ring tension of the four-membered ring, the ring-opening reaction of cyclobutanol can be carried out under mild reaction conditions. In addition, the preparation of cyclobutanol is simple and easy to derivatize. Therefore, the ring-opening functionalization reaction of cyclobutanol is realized by regioselective C- C bond cleavage. It has become one of the most important ways to efficiently synthesize γ-substituted fatty ketones. From the use of early equivalent metal reagents to the realization of the ring-opening reaction of the recent catalytic cycle, the ring-opening functionalization reaction of cyclobutanol has undergone great development. Even so, the application of ring-opening reaction of cyclobutanol is still in the primary stage, and there are still many problems to be optimized and solved, such as the diversity of ring-opening reactions, enantioselective synthesis and its application in complex molecular synthesis. These challenges will also be the focus of future research on ring-opening reactions of cyclic framework compounds. |
| References | [1] Zhang Huanjun, Cheng Xuerui, Ren Yufen, Zhu Xiang, Yuan Chaosheng. In-situ Raman Spectroscopy Study on Temperature Phase Change of Cyclobutanol [J]. Spectroscopy and Spectral Analysis, 2016,02:408-412. [2] Yan Hong, Zhu Chen. Cyclobutanol Ring Opening Functionalization Reaction: A New Strategy for Selective Construction of γ-Substituted Fatty Ketone by C- C Bond Fracture Region [J]. Chemical Progress, 2016,01:1-8. [3] Manganese-catalyzed Ring Opening of Cyclobutanol to Construct γ-Azide Fatty Ketone [J]. Organic Chemistry, 2015,12:2660. |
Last Update：2024-04-10 22:29:15
