Introduction
In a dry 2-l. three-necked, round-bottomed flask, fitted with a liquid-sealed stirrer, a 500-cc. dropping funnel, and an efficient reflux condenser protected at the top with a calcium chloride tube, is placed 400 cc. of absolute alcohol. Through the condenser tube is added 23 g. Read more about 5,5-Dimethyl-1,3-cyclohexanedione(1 gram atom) of clean sodium at such a rate that the solution is kept at the boiling temperature. After the sodium has dissolved completely, 170 g. (1.06 moles) of ethyl malonate is added, and then 100 g. (1.02 moles) of mesityl oxide (Note 1) is added slowly through the dropping funnel.
The solution is refluxed with constant stirring for two hours, after which a solution of 125 g. (2.2 moles) of potassium hydroxide in 575 cc. of water is added and the mixture is stirred and refluxed again on the water bath for six hours.
The mixture while still hot is made just acid to litmus with dilute hydrochloric acid (1 volume concentrated acid to 2 volumes water; sp. gr. 1.055); about 550 cc. is required. The flask is fitted with a condenser set for distillation, and as much alcohol as possible (about 550 cc.) is distilled by heating on a water bath.
The residue in the flask is boiled with about 15 g. of Norite (Note 2), filtered, and the treatment with the decolorizing charcoal repeated. The residue is again neutralized to litmus with dilute hydrochloric acid (about 150 cc.) and again boiled with charcoal.
The hot, neutral or alkaline, yellow filtrate is finally made distinctly acid to methyl orange with additional dilute hydrochloric acid (50 to 100 cc.), boiled for a few minutes, and allowed to cool, whereupon the methone crystallizes. The product is filtered by suction from the acid liquid, washed with ice-cold water, and dried in the air. The yield is 96–122 g. (67–85 per cent of the theoretical amount) (Note 3).
1. Recent developments in the chemistry of Enaminones
This report includes synthetic approaches to enaminones 1 through different methods. The chemical reactivity toward electrophilic and nucleophilic reagents is reported. Photochemical, pericylic, dipolar cycloaddition, reduction and oxidation reactions are also included. It includes 126 references.
2. Section snippets
1. Condensation reactions
Active methylene ketones 2 condense readily with dialkylamino dimethyl acetals 3 to yield the enaminones 1. In general, enaminone formation has been conducted in refluxing aromatic hydrocarbons,5., 6., 7., 8., 9., 10. ethanol,10b ether,11 under nitrogen,12 toluene,8 DMF13 or without solvent.1 Both cyclic and acyclic ketones condense readily under these conditions, the condensation of cyclohexanone 4 with N,N-dimethylformamide dimethyl acetal, for example, (DMF DMA) affording the enaminone 5 in..
2. Reactions with carbon electrophiles
The reaction of the enaminones 1 with trifluoroacetic anhydride has afforded the corresponding trifluoroacetyl derivatives 76.11
Reacting 77 with methyl propionate afforded 79 via the intermediacy of the non-isolable 78 in 44% yield.49
3. Acknowledgements
The authors are grateful to Professor M. H. Elnagdi and Dr Fatima Al-Omran for their help and valuable advice.Read More
Abdel-Zaher A. Elassar was born in 1960 in Monoufia, Egypt. He received his BSc in chemistry (First Class Honours with Distinction from Monoufia University, Egypt, in 1982. Both his MSc (Organic Synthesis) and PhD (Organic Polymer Chemistry) were received from Helwan University Cairo, Egypt, in 1988 and 1993, respectively. He was promoted to the rank of associated professor in 2000. He worked at the National Center of Radiation Research and Technology, Cairo, Egypt (1983) and moved in the same…
3. Notes
- The yield of methone depends on the purity of the mesityl oxide(Org. Syn. Coll. Vol. I, 1941, 345), which should be freshly distilled, the fraction boiling at 126–131°being collected.
- Care is necessary when adding the decolorizing charcoal or the hot acid solution may foam vigorously owing to the liberation of carbon dioxide. A large containershould be used, and the charcoal should be added very slowly.
- The submitters in carrying out this preparation invariably obtained yields ranging from 120 to 128 g.of a product melting between 145° and 147°. Crystallization from about 1 l. of acetonegave 100 g. (70 per cent) of pure white material melting at 147°.
The checkers (using mesityl oxide purchased from the Eastman Kodak Co. and freshly distilled) obtained yields ranging from 96 to 112 g., but their product melted at 147–148° and recrystallization failed to raise the melting point. The melting point of methone is given in the literature as 148–150°.
Working with Hazardous Chemicals
The procedures in Organic Syntheses are intended for use only by persons with proper training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as “Prudent Practices in the Laboratory” (The National Academies Press, Washington, D.C., 2011; the full text can be accessed free of charge at http://www.nap.edu/catalog.php?record_id=12654). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see
In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red “Caution Notes” within a procedure. It is important to recognize that the absence of a caution note does not imply that no significant hazards are associated with the chemicals involved in that procedure.
Prior to performing a reaction, a thorough risk assessment should be carried out that includes a review of the potential hazards associated with each chemical and experimental operation on the scale that is planned for the procedure. Guidelines for carrying out a risk assessment and for analyzing the hazards associated with chemicals can be found in Chapter 4 of Prudent Practices.
The procedures described in Organic Syntheses are provided as published and are conducted at one’s own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
The paragraphs above were added in September, 2014.
The statements above do not supersede any specific hazard caution notes and safety instructions included in the procedure.
4. POTENTIAL HEALTH EFFECTS
ACUTE HEALTH EFFECTS
1. SWALLOWED
The material has NOT been classified as “harmful by ingestion”. This is because of the lack of corroborating animal or human evidence. The material may still be damaging to the health of the individual, following ingestion, especially where pre-existing organ (e.g. liver, kidney) damage is evident. Present definitions of harmful or toxic substances are generally based on doses producing mortality (death) rather than those producing morbidity (disease, ill-health). Gastrointestinal tract discomfort may produce nausea and vomiting. In an occupational setting however, unintentional ingestion is not thought to be cause for concern.Read more Effect 5 5 Dimethyl 1 3 cyclohexanedione
2. EYE
Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals.
3. SKIN
The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting. ! Repeated exposure may cause skin cracking, flaking or drying following normal handling and use. ! Open cuts, abraded or irritated skin should not be exposed to this material. ! Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected.
4. INHALED
Inhalation of vapours may cause drowsiness and dizziness. This may be accompanied by narcosis, reduced alertness, loss of reflexes, lack of coordination and vertigo. ! Inhalation of dusts, generated by the material during the course of normal handling, may be damaging to the health of the individual. !
There is some evidence to suggest that the material can cause respiratory irritation in some persons. The body’s response to such irritation can cause further lung damage. ! Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled.
5. CHRONIC HEALTH EFFECTS
Long-term exposure to the product is not thought to produce chronic effects adverse to the health (as classified using animal models); nevertheless exposure by all routes should be minimized as a matter of course. Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Prime symptom is breathlessness; lung shadows show on X-ray. Read more 5 5 Dimethyl 1 3 cyclohexanedione.
6. PROTECTIVE ACTIONS FOR SPILL
1. FOOTNOTES
- PROTECTIVE ACTION ZONE is defined as the area in which people are at risk of harmful exposure. This zone assumes that random changes in wind direction confines the vapour plume to an area within 30 degrees on either side of the predominant wind direction, resulting in a crosswind protective action distance equal to the downwind protective action distance. read more 5,5-Dimethyl-1,3-cyclohexanedione
- PROTECTIVE ACTIONS should be initiated to the extent possible, beginning with those closest to the spill and working away from the site in the downwind direction. Within the protective action zone a level of vapour concentration may exist resulting in nearly all unprotected persons becoming incapacitated and unable to take protective action and/or incurring serious or irreversible health effects.
- INITIAL ISOLATION ZONE is determined as an area, including upwind of the incident, within which a high probability of localised wind reversal may expose nearly all persons without appropriate protection to life-threatening concentrations of the material.
- SMALL SPILLS involve a leaking package of 200 litres (55 US gallons) or less, such as a drum (jerrican or box with inner containers). Larger packages leaking less than 200 litres and compressed gas leaking from a small cylinder are also considered “small spills”. LARGE SPILLS involve many small leaking packages or a leaking package of greater than 200 litres, such as a cargo tank, portable tank or a “one-tonne” compressed gas cylinder.
- Guide No guide found. is taken from the US DOT emergency response guide book.
- IERG information is derived from CANUTEC – Transport Canada
8. ACUTE EXPOSURE GUIDELINE LEVELS (AEGL) (in ppm)
AEGL 1: The airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic nonsensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
AEGL 2: The airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.
AEGL 3: The airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.
9. Molecules with versatile biological activities bearing antipyrinyl nucleus as pharmacophore
Jyotirmaya Sahoo, … Sudhir Kumar Paidesetty, in European Journal of Medicinal Chemistry, 2020
4.14 Synthesis and antibacterial action of antipyrinylazo subst. dimedone
The attempt of coupling of diazonium salt of 4-aminoantipyrine with dimedone to give 2,3-dimethyl-4-[2-(5,5-dimethyl-2,6-dioxocyclohex-2-ylidene)-hydrazino]-5-oxo-1-phenylpyrazoline 3 by azo coupling reaction was pursued. Further, the hot solution of 2,3-dimethyl-4-[2-(5 5 Dimethyl 1 3 cyclohexanedione-2,6-dioxocyclohex-2-ylidend)-hydrazino]-5-oxo-1-phenylpyrazoline 3 was treated with methanolic solution of phenylhydrazine hydrochloride in presence of acetic acid, sodium acetate and the mixture was refluxed to get 4-{2-[2,6-bis(phenylhydrazono)-5,5,5-Dimethyl-1,3-cyclohexanedione-2-ylidene]hydrazino}-2,3-dimethyl-5-oxo-1-phenylpyrazoline 4.
The ethanolic solution of 2,3-dimethyl-4-[2-(5,5-dimethyl-2,6-dioxocyclohex-2-ylidend)-hydrazino]-5-oxo-1-phenylpyrazoline treated with mixture of hydroxylamine hydrochloride and sodium acetate was refluxed to obtain 4-{2-[2,6-bis(hydroxyimino)-5,5-dimethylcyclohex-2-ylidene]hydrazino}-2,3-dimethyl-5-oxo-1-phenylpyrazoline 5.
The mixture of 2,3-dimethyl-4-[2-(5,5-dimethyl-2,6-dioxocyclohex-2-ylidend)-hydrazino]-5-oxo-1-phenylpyrazoline 4 and hydroxylamine hydrochloride in acetic anhydride was heated after re-crystallization the final product 4-acetoxyimino-6,6-dimethyl-2-(2,3-dimethyl-1-phenylpyrazolin-5-on-4-yl)-4,5,6,7-tetrahydrobenzo-[d] [1–3]triazole 7 was obtained by heating the mixture of product 6 and acetic anhydride (Scheme 20).
The antimicrobial activity of antipyrine derivatives was evaluated against S. aureus, E. coli and C. albicans by agar diffusion method. Ampicillin and clotrimazole was used as standard. The compound 2,3-Dimethyl-4-[2-(5,5-dimethyl-2,6-dioxocyclohex-2-ylidene)hydrazino]-5-oxo-1-phenylpyrazoline 3 showed better antifungal activity against C. albicans than the standard control, whereas the compound 2,3-dimethyl-4-[2-(5,5-dimethyl-2,6-dioxocyclohex-2-ylidene)-hydrazino]-5-oxo-
1-phenylpyrazoline 4, 4-{2-[2,6-Bis(hydroxyimino)-5,5-dimethylcyclohex-2-ylidene]hydrazino}-2,3-dimethyl-5-oxo-1-phenylpyrazoline 5 and 4-acetoxyimino-6,6-dimethyl-2-(2,3-dimethyl-1-phenylpyrazolin-5-on-4-yl)-4,5,6,7-tetrahydrobenzo-[d] [1–3]triazole 7 had moderate antibacterial activity against S. aureus [16].
10.The thio-Claisen rearrangement 1980–2001
Krishna C. Majumdar, Subhojit Ghosh, Manish Ghosh
Various aspects of the thio-Claisen rearrangement along with its synthetic utility are reviewed. The report contains 85 references.
Section snippets
1. Mechanistic aspects
The role of a wide variety of both neutral and anionic nucleophiles12 in the concerted [3,3] sigmatropic rearrangement of phenyl allyl sulfides 1 leading to 2-allylthiophenols 2 has been thoroughly investigated. Scheme 1 illustrates the proposed reaction course and the geometrical details of the transition state involved.
Overman et al.13 have advanced a mechanistic proposal for the cyclisation-induced catalysis of the [3,3] sigmatropic rearrangement in the sulfur series involving the following…
2. Stereoselectivity
The stereospecificity26., 27., 28. of the TCR has been investigated quite thoroughly and this finds use in diastereoselective syntheses. The β-hydroxythioamides 10 undergo di-deprotonation with LDA at −40°C. Allylation of the dilitho species 11 with various allyl bromides affords the α-allyl-β-hydroxy thioamides 13 through a TCR of 12, with preponderant syn diastereoselectivity ranging from 80:20 to 98:2, through the TCR of the S-allylic ketene aminothioacetals (Scheme 6).29
3. Synthesis of natural products
A number of naturally occurring compounds use the TCR in their synthesis. 3-Butenoylthiopyrrolidine 51 reacts43 with 9-bromolimonene 52 in t-butanol in the presence of DBU to furnish the thioamide 53 through a thio-Claisen process. The occurrence of a Cope rearrangement in 53 leads to a diastereomeric mixture of lanceoyl thiopyrrolidine 54 which is finally converted into an (E/Z) mixture of ethyl lanceolate 55 (Scheme 23).
4. Synthesis of sulfur heterocycles
The TCR provides a very efficient synthetic route to a number of sulfur heterocycles (for a preliminary review, see Ref. 50). 2-(Allylthio)tropone 80 and 2-(propargylthio)tropone 81 give51 the 2,3-dihydro-(8H)-cyclohepta[b]thiophene-8-one 82 and (8H)-cyclohepta[b]thiophene-8-one 83, respectively. The corresponding γ-substituted allyl derivatives give poor results when subjected to rearrangement, e.g. 2-(prenylthio)tropone affords isoprene through elimination (Scheme 30).
5. Miscellaneous examples
The synthetic utility of the sulfoxide TCR is manifested in the conversion22 of diallyl sulfide 156 to 2-methylene-5-pentenal 160. Treatment of 156 with N-chlorosuccinimide affords 157. Oxidation of 157 gives the sulfine 158. Exposure of 158 to HgO–BF3 produces 159, which, on dehydrochlorination, with diazabicycloundecene (DBU) finally gives 160. The same transformation cannot be achieved from the corresponding sulfide due to the instability of this compound and its rearrangement products under .
6. Catalysis of the thio-Claisen rearrangement
The catalytic effect on the course of the TCR is much less documented than that of the corresponding oxy- and amino-Claisen rearrangements. Only a few examples are available in the literature. The S-allyl-γ-hydroxyketenedithioacetals 174 undergo80 a facile and diastereoselective TCR into the 2-allyl-3-hydroxydithioesters 175 over different zeolites (Scheme 57).
7. Conclusions
The area of the TCR has not been investigated as thoroughly as those of the corresponding oxy- or amino-Claisen rearrangements. In this review, only recent examples of the utilisation of the TCR in various synthetic strategies has been included. Several stereo-regulated C–C bond formations have involved the use of this reaction. Mechanistic aspects of the rearrangement have been studied in detail. Its synthetic aspects, however, especially the synthesis of sulfur heterocycles and asymmetric..
11.Natural abundance deuterium NMR spectroscopy: Developments and analytical applications in liquids, liquid crystals and solid phases
Philippe Lesot, Jacques Courtieu, in Progress in Nuclear Magnetic Resonance Spectroscopy, 2009
Comparison of averaged (2H/1H)i isotopic ratios measured from the NAD spectrum of methyl linoleate for a recycling time of 1 s (continuous line) and 2 s (dash line) versus the deuterium sites i (2–18). Methyl group 1 was not quantified as it possesses an extra botanical origin. Note the odd/even effect along the aliphatic chain..
Selenoprotein Structure and Function
Ryosuke Masuda, Kei Goto, in Methods in Enzymology, 2022
4.4.2 Protocol for the 1H NMR monitoring of the reaction of Sec–SeOH with dimedone
We examined the 1H NMR monitoring of the reaction of Sec–SeOH 11a with dimedone (16) (Scheme 17) (Masuda, Kimura, et al., 2021). After generation of Sec–SeOH 11a by oxidation of Sec–SeH 10a (14.6 mg, 7.21 μmol) according to the protocol described in Section 4.4.1, a 1H NMR spectrum of the resulting mixture was recorded at − 20 °C (Sec–SeOH 11a and diselenide 36a were observed in 65% and 11% NMR yields, respectively) and then the J-Young NMR sample tube containing the mixture was cooled to − 65 °C in a Dewar bottle. After 10 min, dimedone (16) (9.2 mg, 66 μmol, 9.1 equiv) was added to the mixture at − 65 °C. After 10 min, a 1H NMR spectrum was recorded again at − 20 °C. The formation of selenide 37a, dehydroalanine 14a, diselenide 36a, and Sec–SeOH 11a was observed in 34%, 9%, 16%, and 10% NMR yields, respectively…
12.Synthesis and biological activity of structurally diverse phthalazine derivatives: A systematic review
Jaiprakash Sangshetti, … Devanand B. Shinde, in Bioorganic & Medicinal Chemistry, 2019
2.7 Synthesis of phthalazine-triones
Recently, Khajoee et al., synthesized phthlazine-triones 26 by reacting phthalic anhydride 1 with dimedone 25, aryl
aldehyde and hydrazine hydrate in the presence of a nickel catalyst in acetic acid as depicted in Scheme 7.67
Question
1. What is dimedone used for?
Several biological and medicinal activities have been reported for Dimedone (5 5 Dimethyl 1 3 cyclohexanedione) and its derivatives including antimicrobial [8], [9], [10], anti-cancer [11], anti-inflammation [12], [13], anti-HIV, anti-diabetes [14], antifungal [15], anti-protozoal [16], anti-tuberculosis [17], anti-inflammatory [9], [18], anti- …
2. What is the mechanism of synthesis of dimedone?
The first step of the synthesis of dimedone is a Michael addition, which is then followed by a Dieckmann cyclization, basic ester hydrolysis, and decarboxylation (5) steps, for all of which there are relatively few stage-2 undergraduate laboratory practicals available.14-Jul-2023
3. What is the appearance of Dimedone?
Its white to light yellow crystals have been utilized as substrate in wide range of organic reactions including multi-component transformations. The notability of dimedone is due to the acidic property of its methylene group which is in equilibrium with its tautomeric enol form.
What is 3 5 dimethyl 1 phenylpyrazole?.
4. What is 3 5 dimethyl pyrazole used for?
Uses at industrial sites
This substance is used in the following products: polymers, coating products, fillers, putties, plasters, modelling clay and laboratory chemicals.09-Oct-2024
5. How to prepare 3,5-dimethylpyrazole?
3,5-5 5 Dimethyl 1 3 cyclohexanedione also has been prepared by hydrolysis and decarboxylation of the 1-carbamido- or 1-carboxamidine derivatives, obtained by reaction of semicarbazide7 or aminoguanidine8 with acetylacetone, and from 1,2-pentadien-4-one and hydrazine hydrate.