2033-24-1

Basic information

• Product Name: 2,2-Dimethyl-1,3-dioxane-4,6-dione
• Synonyms: MELDRUMS ACID;'MELDRUM'S ACID';MELDRUM'S ACID;MALONIC ACID CYCLIC ISOPROPYLIDENE ESTER;LABOTEST-BB LT00233174;CYCLIC-ISOPROPYLIDENE MALONATE;CYCL-ISOPROPYLIDENE MALONATE;ISOPROPYLIDENE MALONATE
• CAS NO: 2033-24-1
• Molecular Formula: C₆H₈O₄
• Molecular Weight: 144.13
• EINECS: 217-992-8
• Product Categories: Dioxanes;Dioxanes & Dioxolanes;Drug Discovery;pharmaceutical intermediates;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 2033-24-1.mol
• Article Data: 44

Chemical Properties

• Melting Point: 92-96 °C(lit.)
• Boiling Point: 182.71°C (rough estimate)
• Flash Point: 195.1 °C
• Appearance: Brownish-white to beige-brown/Crystals or Powder
• Density: 1.1311 (rough estimate)
• Vapor Pressure: 1.89E-05mmHg at 25°C
• Refractive Index: 1.4434 (estimate)
• Storage Temp.: 0-6°C
• Solubility: dioxane: soluble5%, clear to very slightly hazy, colorless to fa
• PKA: 5.1(at 25℃)
• Water Solubility: 2.5 g/100 mL (20 ºC)
• Merck: 14,5817
• BRN: 117310
• CAS DataBase Reference: 2,2-Dimethyl-1,3-dioxane-4,6-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 2,2-Dimethyl-1,3-dioxane-4,6-dione(2033-24-1)
• EPA Substance Registry System: 2,2-Dimethyl-1,3-dioxane-4,6-dione(2033-24-1)

Safety Data

• Hazard Codes: Xi,T
• Statements: 36/37/38-45
• Safety Statements: 37/39-24/25-53-45-36-26
• WGK Germany: 3
• RTECS: JH0800000
• F: 10-21
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 2033-24-1(Hazardous Substances Data)

Usage

Chemical Properties

Crystals, white to beige

Uses

Different sources of media describe the Uses of 2033-24-1 differently. You can refer to the following data:
1. Meldrum`s acid is an intermediate for different organic syntheses. For typical reactions please consult the Meldrum`s acid brochure, which you can order. Contact us. Product Data Sheet
2. An antimicrobial agent
3. In organic synthesis as a substitute for acyclic malonic esters and generally as a C3O2 synthon.
4. 2,2-Dimethyl-1,3-dioxane-4,6-dione was used in the synthesis of:macrocyclic β-keto lactone4-pyridyl-substituted heterocycles2-substituted indolesisofraxidin.

Preparation

2,2-Dimethyl-1,3-dioxane-4,6-dione is usually prepared by condensation of malonic acid with acetone in acetic anhydride in the presence of sulfuric acid. Excellent yield of the product was achieved when acetic anhydride was added in a slow, controlled manner to a mixture of acetone, malonic acid and an acid catalyst.

Synthesis Reference(s)

Journal of the American Chemical Society, 70, p. 3426, 1948 DOI: 10.1021/ja01190a060

General Description

2,2-Dimethyl-1,3-dioxane-4,6-dione (Meldrum′s acid) is widely used in organic synthesis, especially for multiple C-C bond formations due to its adequate acidity (pKa 4.83) and steric rigidity. Knoevenagel condensation reaction between aldehydes and Meldrum′s acid are accelerated in ionic liquids.

Flammability and Explosibility

Nonflammable

Purification Methods

Crystallise the dione from Me2CO/H2O. It is a synthon for the C3 malonic acid moiety. [Arnette et al. J Am Chem Soc 106 6759 1984, Bihlmayer et al. Monatsh Chem 98 564 1967, Review: McNab Chem Soc, Rev 7 345 1978, Chan & Huang Synthesis 452 1982, Beilstein 19/5 V 8.]

InChI:InChI=1/C6H8O4/c7-3-5-4(10-5)2-1-8-6(3)9-2/h2-7H,1H2

Synthetic route

2,2-dimethyl-5-(phenyl-λ3-iodaneylidene)-1,3-dioxane-4,6-dione (34107-52-3) → cycl-isopropylidene malonate (2033-24-1) + iodobenzene (591-50-4) + acetone (67-64-1)

Conditions	Yield
With dirhodium tetraacetate In dichloromethane at 20℃; Product distribution;	A 33% B 100% C 5%

5-(bis(4-tert-phenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1,1-bis(4-t-butylphenyl)methane (19099-48-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 99%

5-((2-methoxyphenyl)(phenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + o-benzyl anisole (883-90-9)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 98%

5-(bis(4-methoxyphenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (1190929-81-7) → cycl-isopropylidene malonate (2033-24-1) + 4,4'-dianisylmethane (726-18-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 96%

5-((4-(tert-butyl)phenyl)(phenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1-benzyl-4-tert-butylbenzene (16251-99-3)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 96%

5-((3-methoxyphenyl)(phenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + m-benzylanisole (23450-27-3)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 95%

6,6-dimethyl-4,8-dioxo-5,7-dioxa-1,2-diazaspiro<2.5>oct-1-ene (68695-08-9) → cycl-isopropylidene malonate (2033-24-1)

Conditions	Yield
With benzophenone In methanol Irradiation;	93%

5-(bis(3-methoxyphenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + bis(3-methoxyphenyl)methane (51095-48-8)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 93%

5-(2-(4-isopropylphenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1,4-bis(1-methylethyl)benzene (100-18-5)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethyl acetate at 65℃; under 760.051 Torr; for 96h; Sealed tube;	A n/a B 91%

2,2-dimethyl-5-(2-(4-(octyloxy)phenyl)hexan-2-yl)-1,3-dioxane-4,6-dione (1190929-78-2) → cycl-isopropylidene malonate (2033-24-1) + 1-(hexan-2-yl)-4-(octyloxy)benzene (1190929-84-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 90%

2,2-dimethyl-5-(2-(2-(octyloxy)phenyl)propan-2-yl)-1,3-dioxane-4,6-dione (1190929-75-9) → cycl-isopropylidene malonate (2033-24-1) + 1-isopropyl-2-(octyloxy)benzene (1190929-83-9)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 48h;	A n/a B 90%

5-(2-(4-butylphenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1-butyl-4-(1-methylethyl)benzene (55169-03-4)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 90%

2,2-dimethyl-5-(2-(4-(octyloxy)phenyl)butan-2-yl)-1,3-dioxane-4,6-dione (1190929-77-1) → cycl-isopropylidene malonate (2033-24-1) + 1-(sec-butyl)-4-octyloxybenzene (148924-08-7)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 86%

5-[1-(2-ethylphenyl)-1-methylethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione (1098072-98-0) → cycl-isopropylidene malonate (2033-24-1) + 1-ethyl-2-isopropylbenzene (18970-44-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 83%

2,2-dimethyl-5(1-(4-(octyloxy)phenyl)cyclohexyl)-1,3-dioxane-4,6-dione (1190929-76-0) → cycl-isopropylidene malonate (2033-24-1) + 1-cyclohexyl-4-(octyloxy)benzene (172752-17-9)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 82%

5-(2-(4-isopropoxyphenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1-isopropoxy-4-isopropylbenzene (28530-36-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 82%

5-((4-fluorophenyl)(4-methoxyphenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (1266101-51-2) → cycl-isopropylidene malonate (2033-24-1) + 1-(4-fluorobenzyl)-4-methoxybenzene (38695-26-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 81%

5-((4-fluorophenyl)(phenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (1266101-38-5) → cycl-isopropylidene malonate (2033-24-1) + 4-fluorodiphenylmethane (587-79-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 81%

5-(2-(4-neopentylphenyl)propan-2-yl)-2,2-dimethy-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1-isopropyl-4-neopentylbenzene (37920-33-5)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 81%

2,2-dimethyl-5-(1-methyl-1-phenylethyl)-1,3-dioxane-4,6-dione (81710-07-8) → cycl-isopropylidene malonate (2033-24-1) + Isopropylbenzene (98-82-8)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A 80% B n/a

5-(2-([1,1'-biphenyl]-4-yl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione (1190929-69-1) → cycl-isopropylidene malonate (2033-24-1) + 4-isopropylbiphenyl (7116-95-2)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 80%

5-(2-(3-(tert-butyl)phenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione (1381982-75-7) → cycl-isopropylidene malonate (2033-24-1) + 1-tert-butyl-3-isopropylbenzene (20033-12-9)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethyl acetate at 65℃; under 760.051 Torr; for 24h; Sealed tube;	A n/a B 80%

malonic acid (141-82-2) + acetone (67-64-1) → cycl-isopropylidene malonate (2033-24-1)

Conditions	Yield
With sulfuric acid; acetic anhydride at 60℃;	78%
Stage #1: malonic acid With sulfuric acid; acetic anhydride at 0℃; for 1h; Stage #2: acetone In acetic anhydride at 0℃; for 30h;	77%
With sulfuric acid; acetic anhydride at -5 - 0℃; for 3h;	70.9%

2,2-dimethyl-5-(2-(4-(octyloxy)phenyl)propan-2-yl)-1,3-dioxane-4,6-dione (1190929-65-7) → cycl-isopropylidene malonate (2033-24-1) + 1-isopropyl-4-(octyloxy)benzene (1190929-82-8)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 78%

5-(2-(4-(tert-butyl)phenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione (1381982-70-2) → cycl-isopropylidene malonate (2033-24-1) + p-tert.-Butyl-cumol (4132-49-4)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethyl acetate at 65℃; under 760.051 Torr; for 48h; Sealed tube;	A n/a B 76%

5-(2-(4-isobutylphenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1-isobutyl-4-isopropylbenzene (34349-70-7)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 72%

2,2-dimethyl-5-(3-methyl-2-(4-(octyloxy)phenyl)butan-2-yl)-1,3-dioxane-4,6-dione (1190929-79-3) → cycl-isopropylidene malonate (2033-24-1) + 1-(3-methylbutan-2-yl)-4-(octyloxy)benzene (1190929-85-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 24h;	A n/a B 70%

5-(2-(4-(tert-butoxy)phenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione → cycl-isopropylidene malonate (2033-24-1) + 1-tert-butoxy-4-isopropylbenzene (16215-76-2)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 760.051 Torr; for 48h;	A n/a B 70%

methanol (67-56-1) + 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dion (7270-63-5) → 6,6-dimethyl-4,8-dioxo-5,7-dioxa-1,2-diazaspiro<2.5>oct-1-ene (68695-08-9) + cycl-isopropylidene malonate (2033-24-1) + methyl 2,2-dimethyl-5-oxo-1,3-dioxolane-4-carboxylate (62609-79-4) + 2,2-dimethyl-4,6-dioxo-5-methoxy-1,3-dioxane (97801-91-7)

Conditions	Yield
for 1.16667h; Product distribution; Irradiation;	A 4.5% B 3% C 64% D 2.5%
In tetrahydrofuran at 18 - 20℃; for 9h; UV-irradiation;	A 23% B 8% C 25% D n/a

pyrrolidine (123-75-1) + cycl-isopropylidene malonate (2033-24-1) + 2-Methylbutyraldehyde (96-17-3, 57456-98-1) → 2,2-Dimethyl-5-(2-methyl-1-pyrrolidin-1-yl-butyl)-[1,3]dioxane-4,6-dione

Conditions	Yield
In diethyl ether for 0.166667h;	100%

pyrrolidine (123-75-1) + cycl-isopropylidene malonate (2033-24-1) + d,l-2-ethylhexanal (123-05-7) → 5-(2-Ethyl-1-pyrrolidin-1-yl-hexyl)-2,2-dimethyl-[1,3]dioxane-4,6-dione (93498-12-5)

Conditions	Yield
In diethyl ether for 0.166667h;	100%

pyrrolidine (123-75-1) + cycl-isopropylidene malonate (2033-24-1) + benzaldehyde (100-52-7) → 2,2-Dimethyl-5-(phenyl-pyrrolidin-1-yl-methyl)-[1,3]dioxane-4,6-dione (93498-11-4)

Conditions	Yield
In diethyl ether for 0.166667h;	100%

pyrrolidine (123-75-1) + cycl-isopropylidene malonate (2033-24-1) + propionaldehyde (123-38-6) → 2,2-Dimethyl-5-(1-pyrrolidin-1-yl-propyl)-[1,3]dioxane-4,6-dione (93498-07-8)

Conditions	Yield
In diethyl ether for 0.166667h;	100%

pyrrolidine (123-75-1) + cycl-isopropylidene malonate (2033-24-1) + butyraldehyde (123-72-8) → 2,2-Dimethyl-5-(1-pyrrolidin-1-yl-butyl)-[1,3]dioxane-4,6-dione (93498-08-9)

Conditions	Yield
In diethyl ether for 0.166667h;	100%

pyrrolidine (123-75-1) + cycl-isopropylidene malonate (2033-24-1) + isobutyraldehyde (78-84-2) → 2,2-Dimethyl-5-(2-methyl-1-pyrrolidin-1-yl-propyl)-[1,3]dioxane-4,6-dione (93498-09-0)

Conditions	Yield
In diethyl ether for 0.166667h;	100%

4-methyleneoxetan-2-one (674-82-8) + cycl-isopropylidene malonate (2033-24-1) → 2,2-dimethyl-5-(1-hydroxy-3-oxobutylidene)-1,3-dioxane-4,6-dione (84257-12-5)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 2h;	100%
Stage #1: 4-methyleneoxetan-2-one; cycl-isopropylidene malonate With triethylamine In dichloromethane at 0 - 20℃; for 2h; Stage #2: With hydrogenchloride In dichloromethane; water	100%
With triethylamine In dichloromethane at 20℃;	100%

cycl-isopropylidene malonate (2033-24-1) + 1,1-bis(phenylsulfonyl)ethylene (39082-53-6) → 5-(2,2-Bis-benzenesulfonyl-ethyl)-2,2-dimethyl-[1,3]dioxane-4,6-dione (87625-91-0)

Conditions	Yield
N-benzyl-trimethylammonium hydroxide In 1,4-dioxane	100%

cycl-isopropylidene malonate (2033-24-1) + (+/-)-3-Methyl-4,4,4-trichlorobutanoyl Chloride (91238-98-1) → 2,2-Dimethyl-5-(4,4,4-trichloro-3-methyl-butyryl)-[1,3]dioxane-4,6-dione (91265-41-7)

Conditions	Yield
With pyridine In dichloromethane 1. 1 h/-5 deg C 2. 30 min/room temperature;	100%

cycl-isopropylidene malonate (2033-24-1) + Rhodinoic acid chloride (88373-61-9) → 5-(3,7-Dimethyl-oct-7-enoyl)-2,2-dimethyl-[1,3]dioxane-4,6-dione (88373-62-0)

Conditions	Yield
With pyridine In dichloromethane at 0℃;	100%

cycl-isopropylidene malonate (2033-24-1) + C18H14N4O2 (107798-95-8) → 2-<(4,4-dimethyl-2,6-dioxo-3,5-dioxanylidene)methyl>-3-methylindole (103865-88-9)

Conditions	Yield
With triethylamine In tetrahydrofuran for 0.333333h; Ambient temperature;	100%
With triethylamine In tetrahydrofuran for 0.5h; Ambient temperature; Yield given;

cycl-isopropylidene malonate (2033-24-1) + Hexanoyl chloride (142-61-0) → 2,2-dimethyl-5-(1-oxohexyl)-1,3-dioxane-4,6-dione (254907-27-2)

Conditions	Yield
With dmap In dichloromethane at 20℃; for 16h; Inert atmosphere;	100%
With pyridine In dichloromethane	62%
With pyridine In dichloromethane Ambient temperature;

cycl-isopropylidene malonate (2033-24-1) + orthoformic acid triethyl ester (122-51-0) → 5-(ethoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (15568-86-2)

Conditions	Yield
at 80℃; for 3h;	100%
With zinc diacetate at 90℃; for 1h; Condensation;	85%
at 105℃; for 2h;	80%

cycl-isopropylidene malonate (2033-24-1) + phenylacetyl chloride (103-80-0) → 5-(1-hydroxy-2-phenylethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (66696-84-2)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; Acylation;	100%
With dmap Inert atmosphere;	75%
Stage #1: cycl-isopropylidene malonate With pyridine In dichloromethane at 0℃; Stage #2: phenylacetyl chloride In dichloromethane at 0 - 20℃; Stage #3: With hydrogenchloride In dichloromethane; water Cooling with ice;	71%

cycl-isopropylidene malonate (2033-24-1) + tert-butyl alcohol (75-65-0) → mono-tert-butyl malonate (40052-13-9)

Conditions	Yield
for 6h; Reflux;	100%
Reflux;	97%
Stage #1: cycl-isopropylidene malonate; tert-butyl alcohol for 5h; Reflux; Stage #2: With ammonia; water In ethanol at 5℃; for 0.0833333h; Stage #3: With hydrogenchloride In water	62%

cycl-isopropylidene malonate (2033-24-1) → 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dion (7270-63-5)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; 4-toluenesulfonyl azide; triethylamine for 3h; Ambient temperature;	100%
With 2-azido-1,3-dimethylimidazolinium chloride; triethylamine In tetrahydrofuran at 0℃; for 0.166667h;	95%
With 2-azido-1,3-dimethylimidazolinium chloride; triethylamine In tetrahydrofuran at 0℃; for 0.166667h; Inert atmosphere;	95%

cycl-isopropylidene malonate (2033-24-1) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-[1-benzyl-2-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester (109579-08-0)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 16h;	100%
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 12h; Inert atmosphere;	95%
Stage #1: cycl-isopropylidene malonate; N-tert-butoxycarbonyl-L-phenylalanine With dmap In dichloromethane for 0.166667h; Cooling with ice; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane for 10h; Cooling with ice;	77%

cycl-isopropylidene malonate (2033-24-1) + cyclopropanecarboxylic acid chloride (4023-34-1) → 5-(cyclopropyl(hydroxy)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (146380-13-4)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; Acylation;	100%
Stage #1: cycl-isopropylidene malonate With pyridine In dichloromethane at 0℃; for 0.25h; Stage #2: cyclopropanecarboxylic acid chloride In dichloromethane at 0 - 20℃; for 3h;	60%
With pyridine In dichloromethane at 0 - 20℃; for 3h; Acylation;

cycl-isopropylidene malonate (2033-24-1) + 4-hydroxy-benzaldehyde (123-08-0) → 5-(4-hydroxy-benzylidene)-2,2-dimethyl-[1,3]dioxane-4,6-dione (17474-27-0)

Conditions	Yield
at 50℃; for 1h; Knoevenagel condensation;	100%
In water; toluene at 23 - 33℃; for 4.66667h; Knoevenagel condensation; Large scale reaction;	99%
With cobalt(III) oxide In water for 0.0833333h; Knoevenagel Condensation; Reflux;	99%

cycl-isopropylidene malonate (2033-24-1) + 4-dimethylamino-benzaldehyde (100-10-7) → 5-(4-N,N-dimethylaminobenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (15795-57-0)

Conditions	Yield
at 50℃; for 1h; Knoevenagel condensation;	100%
With ethylammonium nitrate at 20℃; for 0.5h; Knoevenagel condensation;	97%
In various solvent(s) at 20℃; for 0.5h; Knoevenagel condensation;	97%

cycl-isopropylidene malonate (2033-24-1) + isopropyl alcohol (67-63-0) → i-propyl malonic half ester (56766-77-9)

Conditions	Yield
In acetonitrile for 22h; Heating;	100%
Reflux;	76%
In toluene for 5h; Heating;

cycl-isopropylidene malonate (2033-24-1) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (2'S)-5-<(1-hydroxy-3-phenyl-2-t-butoxycarbonylamino)-propylidene>-2,2-dimethyl-1,3-dioxane-4,6-dione (112700-36-4, 112700-37-5)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;	100%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 25℃; for 14h; Inert atmosphere;
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;

cycl-isopropylidene malonate (2033-24-1) + Boc-D-Phe-OH (18942-49-9) → 5-[(2R)-2-(tert-Butoxycarbonylamino)-1-hydroxy-3-phenylpropylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (112700-37-5)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;	100%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 2h;

cycl-isopropylidene malonate (2033-24-1) + 2-methyl-benzyl alcohol (89-95-2) → 2-oxo-2H-chromene-3-carboxylic acid (531-81-7)

Conditions	Yield
With piperdinium acetate In ethanol for 2h; Heating;	100%
With piperidine; acetic acid In benzene Knoevenagel condensation; Heating;	92%
With lithium perchlorate for 0.0138889h; Irradiation;	89%

cycl-isopropylidene malonate (2033-24-1) + 3-methoxy-2-hydroxybenzaldehyde (148-53-8) → 8-methoxy-2-oxo-2H-chromene-3-carboxylic acid (2555-20-6)

Conditions	Yield
With piperdinium acetate In ethanol for 2h; Heating;	100%
In water for 1h; Reflux;	99%
With β‐cyclodextrin In water at 70℃; for 0.25h; Green chemistry;	97%

cycl-isopropylidene malonate (2033-24-1) + Farnesol (106-28-5) → 3-oxo-3-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyloxy)propanoic acid

Conditions	Yield
In toluene at 100℃; Inert atmosphere;	100%
In toluene Heating;	85%

cycl-isopropylidene malonate (2033-24-1) + [3-(3,5-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-benzyloxy)-5-hydroxymethyl-phenyl]-methanol (642442-36-2) → Malonic acid mono-[3-(3,5-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-benzyloxy)-5-(2-carboxy-acetoxymethyl)-benzyl] ester

Conditions	Yield
at 120℃; for 4h;	100%

cycl-isopropylidene malonate (2033-24-1) + {3-[3,5-bis-(3,5-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-benzyloxy)-benzyloxy]-5-hydroxymethyl-phenyl}-methanol (642442-37-3) → Malonic acid mono-[3-[3,5-bis-(3,5-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-benzyloxy)-benzyloxy]-5-(2-carboxy-acetoxymethyl)-benzyl] ester

Conditions	Yield
at 120℃; for 4h;	100%

cycl-isopropylidene malonate (2033-24-1) + C113H164O41 → C119H168O47

Conditions	Yield
at 120℃; for 4h;	100%

Upstream product

• 594-71-8 2-chloro-2-nitro-propane 
• 996-82-7 sodium diethylmalonate 
• 141-82-2 malonic acid 
• 67-64-1 acetone 
• 105-53-3 diethyl malonate 
• 67-56-1 methanol 
• 7270-63-5 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dion 
• 7664-93-9 sulfuric acid 
• 108-24-7 acetic anhydride 
• 64-17-5 ethanol 
• 68695-08-9 6,6-dimethyl-4,8-dioxo-5,7-dioxa-1,2-diazaspiro<2.5>oct-1-ene 
• 1266101-51-2 5-((4-fluorophenyl)(4-methoxyphenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 1266101-38-5 5-((4-fluorophenyl)(phenyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 1190929-77-1 2,2-dimethyl-5-(2-(4-(octyloxy)phenyl)butan-2-yl)-1,3-dioxane-4,6-dione 

Downstream Products

• 70912-54-8 5-azepan-2-ylidene-2,2-dimethyl-[1,3]dioxane-4,6-dione 
• 67996-11-6 5-<1H-indol-3-yl(phenyl)methyl>-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 67996-13-8 5-<(2,5-dimethoxyphenyl)-1H-indol-3-ylmethyl>-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 93498-11-4 2,2-Dimethyl-5-(phenyl-pyrrolidin-1-yl-methyl)-[1,3]dioxane-4,6-dione 
• 86193-13-7 5-[2,3-Bis-(4-methoxy-phenyl)-1-oxo-1H-indolizin-7-ylidene]-2,2-dimethyl-[1,3]dioxane-4,6-dione 
• 86193-18-2 2,2-Dimethyl-5-[1-oxo-2,3-bis-(2,4,6-trimethyl-phenyl)-1H-indolizin-7-ylidene]-[1,3]dioxane-4,6-dione 
• 86222-47-1 2,2-Dimethyl-5-(1-oxo-2,3-diphenyl-1H-indolizin-7-ylidene)-[1,3]dioxane-4,6-dione 
• 86193-36-4 5-(3,7-dihydro-1,2-diphenyl-3-oxoindolizin-7-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 72651-97-9 5-(furan-2-ylmethyl)-2,2-dimethyl[1,3]dioxane-4,6-dione 
• 15875-49-7 5-furfurylidene-2,2-dimethyl-[1,3]dioxane-4,6-dione 
• 15875-50-0 2,2-dimethyl-5-thiophen-2-ylmethylene-[1,3]dioxane-4,6-dione 
• 83260-82-6 2,2-dimethyl-5-(quinolin-2-yl)-1,3-dioxane-4,6-dione 
• 86728-40-7 ethyl 3-oxo-4-(thiophen-2-yl)butanoate 
• 67-64-1 acetone 

Relevant articles and documents

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Search for dioxocarbenes in photochemical reactions of 5-diazo-4,6-dioxo-1, 3-dioxanes, associated diazirines, and S-ylides

On direct photolysis of 2,2-dialkyl-5-diazo-4,6-dioxo-1,3-dioxanes in the presence of pyridine, methanol or dimethyl sulfide as carbene traps, the yield of 'carbene' products does not exceed 27-28%. At the same time photochemical transformations of the re

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IMPROVED METHOD OF SYNTHESIZING 2,2-DIMETHYL-4,6-DIOXO-1,3-DIOXANE (MELDRUM'S ACID)

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Rhodium(II)-catalyzed olefin cyclopropanation with the phenyliodonium ylide derived from Meldrum's acid

The phenyliodonium ylide 3a derived from Meldrum's acid reacts with olefins in the presence of Rh(II) carboxylate catalysts to afford cyclopropanes. The reaction is stereospecific. Enantioselectivities of up to 63% have been observed for the cyclopropanation of pent-1-ene. No 1,3-cycloadducts are formed between 3a and polarized olefins such as furan or 2,3-dihydrofuran.

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Chemical synthesis, molecular docking and MepA efflux pump inhibitory effect by 1,8-naphthyridines sulfonamides

This study aimed to evaluate the antibacterial activity and to verify, in silico and in vitro, the inhibition of efflux mechanisms using a series of synthesized 1,8-naphthyridines sulfonamides against Staphylococcus aureus strains carrying MepA efflux pumps. The chemical synthesis occurred through the thermolysis of the Meldrum's acid adduct. The sulfonamide derivatives were obtained by the sulfonylation of 2-amino-5?chloro-1,8-naphthyridine with commercial benzenesulfonyl chloride. Antibacterial activity was assessed by the broth microdilution test. Efflux pump inhibitory capacity was evaluated in silico by molecular docking and in vitro by analyzing synergistic effects on ciprofloxacin and ethidium bromide (EtBr) and by EtBr fluorescence emission assays. The following 1,8-naphthyridines were synthesized: 4-methyl-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10a); 2,5-dichloro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10b); 4-fluoro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10c); 2,3,4-trifluoro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10d); 3-trifluoromethyl-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10e); 4?bromo-2,5-difluoro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10f). The 1,8-naphthyridines derivatives associated with sulfonamides did not show antibacterial activity. However, they showed a favorable pharmacokinetic profile with possible MepA efflux pump inhibitory action, demonstrated in molecular docking. In addition to the promising results in reducing the concentration of intracellular EtBr. 1,8-naphthyridines act as putative agents in the inhibitory action of the MepA efflux pump.

Enhancement of anticancer potential of pterostilbene derivative by chalcone hybridization

Pterostilbene, a natural metabolite of resveratrol, has been indicated as a potent anticancer molecule. Recently, several pterostilbene derivatives have been reported to exhibit better anticancer activities than that of the parent pterostilbene molecule. In the present study, a series of pterostilbene derivatives were designed and synthesized by the hybridization of pterostilbene, chalcone, and cinnamic acid. The cytotoxic effect of these hybrid molecules was determined using two oral cancer cell lines, HSC-3 and OECM-1. (E)-3-(2-((E)-4-Hydroxystyryl)-4,6-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (4d), with IC50 of 16.38 and 18.06 μM against OECM-1 and HSC-3, respectively, was selected for further anticancer mechanism studies. Results indicated that compound 4d effectively inhibited cell proliferation and induced G2/M cell cycle arrest via modulating p21, cyclin B1, and cyclin A2. Compound 4d ultimately induced cell apoptosis by reducing the expression of Bcl-2 and surviving. In addition, cleavage of PARP and caspase-3 were enhanced following the treatment of compound 4d with increased dose. To conclude, a number of pterostilbene derivatives were discovered to possess potent anticancer potentials. Among them, compound 4d was the most active, more active than the parent pterostilbene.