106-02-5

Basic information

• Product Name: Cyclopentadecanolide
• Synonyms: Pentadecanoicacid, 15-hydroxy-, x-lactone (6CI,7CI);1,15-Pentadecanolide;1-Oxacyclohexadecan-2-one;15-Hydroxypentadecanoic acid lactone;15-Pentadecanolide;15-Pentadodecanolactone;2-Pentadecalone;CPE 215;Oxacyclohexadecan-2-one;Exaltolide;Muskalactone;NSC 36763;Pentadecalactone;Pentadecanolactone;Pentadecanolide;Pentalide;Thibetolide;cpd Supra;w-Pentadecalactone
• CAS NO: 106-02-5
• Molecular Formula: C₁₅H₂₈O₂
• Molecular Weight: 252.3923
• EINECS: 203-354-6
• Product Categories: Biochemicals and Reagents;Building Blocks;Carbonyl Compounds;Chemical Synthesis;Fatty Acids and conjugates;Fatty Acyls;Lactones;Lipids;Organic Building Blocks;Others;Saturated Fatty Acids and Derivatives
• Mol File: 106-02-5.mol

Chemical Properties

• Melting Point: 32-38℃
• Boiling Point: 344.797 °C at 760 mmHg
• Flash Point: 143.392 °C
• Appearance: white crystalline low melting solid
• Density: 0.885 g/cm³
• Vapor Pressure: 6.18E-06mmHg at 25°C
• Refractive Index: 1.457
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform, Ethyl Acetate, Methanol (Slightly)
• Water Solubility: Soluble in alcohol, dipropylene glycol. Insoluble in water.
• Merck: 14,3910
• BRN: 143710
• CAS DataBase Reference: Cyclopentadecanolide(CAS DataBase Reference)
• NIST Chemistry Reference: Cyclopentadecanolide(106-02-5)
• EPA Substance Registry System: Cyclopentadecanolide(106-02-5)

Safety Data

• Safety Statements: S24/25:
• WGK Germany: 1
• RTECS: RN9775000
• TSCA: Yes
• Hazardous Substances Data: 106-02-5(Hazardous Substances Data)

Usage

Chemical Properties

Different sources of media describe the Chemical Properties of 106-02-5 differently. You can refer to the following data:
1. white crystalline low melting solid
2. Cyclopentadecanolide occurs in small quantities in, for example, angelica root oil. It forms colorless crystals (mp 37–38°C) with a delicate, musk-like odor.
3. ω-Pentadecalactone has an extraordinarily persistent, musk-like odor.

Occurrence

Originally reported found in the essential oil from angelica roots.

Uses

Different sources of media describe the Uses of 106-02-5 differently. You can refer to the following data:
1. As a fixative in perfumery.
2. Pentadecanolide is a monomer used to make PGA-co-pentadecalactone polymers to be used in the development of directly compressed prolonged release tablets of slightly soluble drugs such as ketoprofen.
3. Pentadecanolide may be used for the synthesis of poly(pentadecanolide) (PPDL) by Novozyme 435 catalyzed ring-opening polymerization. It may be employed as starting reagent for the synthesis of terminally-branched iso-fatty acids (iso-C15-C17).

Preparation

The main industrial syntheses start from compounds produced from cyclododecatriene: either by ring expansion of cyclododecanone or by depolymerization of polyesters of 15-hydroxypentadecanoic acid (from 1,12-dodecanediol).

Aroma threshold values

Detection: 1 to 4 ppb

Taste threshold values

Taste characteristics at 75 ppm: vanilla bean, powdery helioropine, creamy and licorice.

Synthesis Reference(s)

Tetrahedron Letters, 34, p. 6107, 1993 DOI: 10.1016/S0040-4039(00)61741-0The Journal of Organic Chemistry, 50, p. 2394, 1985 DOI: 10.1021/jo00213a044

General Description

Pentadecanolide is one of the major components, isolated from the root of Angelica archangelica L., species. It is a synthetic musk, which exists as a widespread contaminant in the environment.

Flammability and Explosibility

Nonflammable

Trade name

Macrolide? (Symrise), Exaltolide?, Exaltolide?Total (Firmenich), Pentalide (Soda Aromatic).

Purification Methods

It has been recrystallised from MeOH (4 parts) at -15o. [Hundieck

InChI:InChI=1/C16H28O2/c17-16-14-12-10-8-6-4-2-1-3-5-7-9-11-13-15(14)18-16/h14-15H,1-13H2/t14-,15-/m0/s1

Synthetic route

15-pentadecyn-2-olide → pentadecanolide (106-02-5)

Conditions	Yield
With hydrogen; platinum(IV) oxide	100%

15-hydroxylpentadecanoic acid (4617-33-8) → pentadecanolide (106-02-5) + 1,17-dioxa-cyclodotriacontane-2,18-dione (659-76-7)

Conditions	Yield
With p-nitrobenzoic anhydride; scandium tris(trifluoromethanesulfonate) In tetrahydrofuran; acetonitrile Heating; Yields of byproduct given;	A 99% B n/a
With dmap; 2-methyl-6-nitrobenzoic anhydride In dichloromethane at 20℃; for 15h;	A 92% B 1%
With dmap; di-2-thienyl carbonate; hafnium(IV) trifluoromethanesulfonate In toluene; acetonitrile at 100℃; for 5h;	A 92% B n/a

(E)-6-pentadecen-15-olide (63294-84-8) → pentadecanolide (106-02-5)

Conditions	Yield
With hydrogen; palladium-barium carbonate under 1520 Torr; for 3h; Ambient temperature;	99%

(E/Z)-oxacyclohexadec-11-en-2-one (76293-72-6, 76293-73-7, 4941-77-9) → pentadecanolide (106-02-5)

Conditions	Yield
With palladium on activated charcoal; hydrogen In ethyl acetate at 20℃; under 760.051 Torr; for 16h; Solvent; Concentration; Schlenk technique; Glovebox;	99%
With hydrogen; palladium on activated charcoal under 760 Torr;	94%
With hydrogen; palladium on activated charcoal	94%
With hydrogen; platinum(IV) oxide under 760 Torr;
With 5%-palladium/activated carbon; hydrogen In methanol at 25℃; for 24h;	89.2 %Chromat.

E-Pentadec-2-ene-15-olide (87227-39-2) → pentadecanolide (106-02-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal	99%
With hydrogen; palladium on activated charcoal In ethyl acetate at 20℃; under 760 Torr; for 3h;	98%
With hydrogen; palladium on activated charcoal In ethanol; ethyl acetate for 48h; Ambient temperature;	48 mg

15-hydroxylpentadecanoic acid (4617-33-8) → pentadecanolide (106-02-5)

Conditions	Yield
With dmap; polymer bound carbodiimide; 4-(dimethylamino)pyridine hydrochloride In tetrahydrofuran; chloroform Cyclization; lactonisation; Heating;	97%
With dmap; 4-(dimethylamino)pyridine hydrochloride; dicyclohexyl-carbodiimide In tetrahydrofuran; chloroform Heating;	95%
With dmap; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In tetrahydrofuran; chloroform for 18h; Reflux; Inert atmosphere;	95%

(Z)-Oxacyclohexadec-6-en-2-one (195320-68-4) → pentadecanolide (106-02-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal under 760 Torr;	95%
With hydrogen; palladium on activated charcoal	95%

trimethylsilyl 15-(trimethylsiloxy)pentadecanoate (93472-40-3) → pentadecanolide (106-02-5)

Conditions	Yield
dipropylboryl triflate In toluene Heating;	94%

15-hydroxypentadecanoic acid butyl ester → pentadecanolide (106-02-5)

Conditions	Yield
With titanium(IV) isopropylate at 70 - 250℃; under 3.75038 Torr; for 0.333333h; Reagent/catalyst; Inert atmosphere;	92.9%

12-iodo-15-pentadecanolide (118072-05-2) → pentadecanolide (106-02-5)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene Irradiation;	92%
With 2,2'-azobis(isobutyronitrile); iodine; tri-n-butyl-tin hydride; 1,8-diazabicyclo[5.4.0]undec-7-ene 1.) THF, reflux, 40 min, 2.) THF, ether; Multistep reaction;

(14-Carboxy-tetradecyl)-diphenyl-sulfonium; perchlorate → pentadecanolide (106-02-5)

Conditions	Yield
With potassium carbonate In acetone for 12h; Heating;	92%
With potassium carbonate In acetone for 48h; Heating; Yield given;

1-(N,4-dimethylphenylsulfonylamino)vinyl 15-hydroxypentadecanoate → pentadecanolide (106-02-5) + N-methyl-N-tosylacetamide (16697-83-9)

Conditions	Yield
With camphor-10-sulfonic acid In dichloromethane at 20℃; for 4h;	A 92% B n/a

1-(N,4-dimethylphenylsulfonylamino)vinyl 15-hydroxypentadecanoate → pentadecanolide (106-02-5)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane at 20℃;	92%

15-(tert-butyldimethylsilyloxy)-pentadecanoic acid (77744-43-5) → pentadecanolide (106-02-5)

Conditions	Yield
With tetrabutylammonium tetrafluoroborate; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In chloroform for 18h; Reflux; Inert atmosphere;	91%
Multi-step reaction with 4 steps 1.1: n-BuLi / diethyl ether / 0 °C 1.2: (COCl)2; DMF / diethyl ether 2.1: Et3N / CH2Cl2 / 0 - 20 °C 3.1: 96 percent / 3HF*Et3N / acetonitrile / 20 °C 4.1: 58 percent / Cu(OTf)2 / tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-BuLi / diethyl ether / 0 °C 1.2: (COCl)2; DMF / diethyl ether 2.1: Et3N / CH2Cl2 / 0 - 20 °C 3.1: 57 percent / 3HF*Et3N / acetonitrile / 20 °C 4.1: 83 percent / Cu(OTf)2 / tetrahydrofuran / 20 °C View Scheme

12-oxo-15-pentadecanolide (38223-29-9) → pentadecanolide (106-02-5)

Conditions	Yield
With hydrogenchloride; zinc In acetic anhydride at 0 - 5℃; for 1h;	90%
With hydrogenchloride; zinc In toluene at 0℃;	84%
With sodium cyanoborohydride; toluene-4-sulfonic acid; toluene-4-sulfonic acid hydrazide 1.) DMF, sulfolane, 15 min., 2.) cyclohexane, reflux, 4 h;	50%
Multi-step reaction with 2 steps 1: methanol / 0.67 h / Heating 2: <<(C6H5)3P>Cu>BH4 / CHCl3 / 4 h / Heating View Scheme

15-Hydroxy-pentadecanoic acid (Z)-2-dimethylcarbamoyl-1-methyl-vinyl ester (89611-22-3) → pentadecanolide (106-02-5) + N,N-Dimethylacetoacetamid (2044-64-6)

Conditions	Yield
With magnesium bromide In tetrahydrofuran at 55℃; other solvents, temperatures and reagent;	A 90% B n/a

13-Benzenesulfonyl-oxacyclohexadecan-2-one (81238-39-3) → pentadecanolide (106-02-5)

Conditions	Yield
With disodium hydrogenphosphate; sodium amalgam In methanol; 1,2-dimethoxyethane at -25℃; for 3h;	90%

Acrylic acid 12-iodo-dodecyl ester (109182-98-1) → pentadecanolide (106-02-5) + 1,17-dioxa-cyclodotriacontane-2,18-dione (659-76-7)

Conditions	Yield
With sodium cyanoborohydride In methanol for 3h; Ambient temperature; Irradiation;	A 90% B 7 % Chromat.

trimethylsilyl 15-(trimethylsiloxy)pentadecanoate (93472-40-3) → pentadecanolide (106-02-5) + 1,17-dioxa-cyclodotriacontane-2,18-dione (659-76-7)

Conditions	Yield
With 4-(trifluoromethyl)benzoic anhydride; silver perchlorate; titanium tetrachloride In dichloromethane for 3h; Ambient temperature;	A 89% B 4%
With 4-(trifluoromethyl)benzoic anhydride; silver perchlorate; titanium tetrachloride In dichloromethane; toluene at 20℃; for 33h;	A 89% B 2%

Z-oxacyclohexadec-3-en-2-one (173790-14-2) → pentadecanolide (106-02-5)

Conditions	Yield
With samarium diiodide; 2,4-dichlorophenoxyacetic acid dimethylamine; tert-butyl alcohol In tetrahydrofuran for 0.5h; Ambient temperature;	88%

methyl 15-hydroxypentadecanoate (76529-42-5) → pentadecanolide (106-02-5)

Conditions	Yield
With Lipase B immobilized on acrylic resin from Candida antarctica In cyclohexane; water at 40℃; for 2h; Enzymatic reaction;	88%
Multi-step reaction with 4 steps 1: Imidazole / dimethylformamide 2: 5.0 M NaOH / tetrahydrofuran; methanol; H2O / 7 h 3: 1.) DCC, DMAP; 2.) CH3COOH / 1.) THF, -25 deg C, 4 days; 2.) H2O, room temp., 8 h 4: 45 percent Chromat. / t-BuOK / benzene; tetrahydrofuran View Scheme
Multi-step reaction with 4 steps 1: Imidazole / dimethylformamide 2: 5.0 M NaOH / tetrahydrofuran; methanol; H2O / 7 h 3: 1.) DCC, DMAP; 2.) CH3COOH / 1.) THF, -25 deg C, 4 days; 2.) H2O, room temp., 8 h 4: 74 percent / t-BuOK, molecular sieves / benzene; tetrahydrofuran / Heating; also without molecuar sieves and reflux View Scheme
Multi-step reaction with 4 steps 1: Imidazole / dimethylformamide 2: 5.0 M NaOH / tetrahydrofuran; methanol; H2O / 7 h 3: 1.) 1-<3-(Dimethylamino)propyl>-3-ethylcarboximide hydrochloride, DMAP; 2.) CH3COOH / 1.) DMF, 1 day; 2.) H2O, 12 h 4: 81 percent / t-BuOK, molecular sieves / benzene; tetrahydrofuran / Heating; also without molecuar sieves and reflux View Scheme
Multi-step reaction with 4 steps 1: Imidazole / dimethylformamide 2: 5.0 M NaOH / tetrahydrofuran; methanol; H2O / 7 h 3: 1.) DCC, DMAP; 2.) CH3COOH / 1.) THF, -25 deg C, 5 days; 2.) THF-H2O, room temp., 20 h 4: 43 percent Chromat. / t-BuOK, 19-crown-6 / benzene; tetrahydrofuran View Scheme

cyclopentadecanone (502-72-7) → pentadecanolide (106-02-5)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 108h;	86%
Stage #1: cyclopentadecanone With N-hydroxyphthalimide; 1,1-Diphenylmethanol; 2,2'-azobis(isobutyronitrile); oxygen In acetonitrile at 75℃; under 760.051 Torr; for 22h; Baeyer-Villiger oxidation; Stage #2: With 1,1,1,3',3',3'-hexafluoro-propanol; toluene-4-sulfonic acid at 60℃; Baeyer-Villiger oxidation; Inert atmosphere;	70%
With potassium peroxomonosulphate; sulfuric acid; Petroleum ether at 50 - 65℃;

15-bromo-pentadecanoic acid (56523-59-2) → pentadecanolide (106-02-5)

Conditions	Yield
With tetraoctylammonium (2-pyrrolidonide) In N,N-dimethyl-formamide for 24h; Ambient temperature;	84%
With potassium carbonate In dimethyl sulfoxide at 75℃; for 4h;	78%
With potassium carbonate; butanone

15-hydroxylpentadecanoic acid (4617-33-8) + 2-chloro-1-methyl-pyridinium iodide (14338-32-0) → pentadecanolide (106-02-5)

Conditions	Yield
With triethylamine In acetonitrile	84%
With tributyl-amine In acetonitrile	74%
With triethylamine In toluene	63%.

15-hydroxy-pentadecanoic acid 6-methyl-pyridin-2-yl ester (874583-99-0) → pentadecanolide (106-02-5)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In tetrahydrofuran at 20℃;	83%

15-Hydroxy-pentadecanethioic acid S-[(2R,3aR,19aS)-1-(tetradecahydro-4,7,10,13,16,19-hexaoxa-cyclopentacyclooctadecen-2-yl)methyl] ester (77744-39-9) → pentadecanolide (106-02-5)

Conditions	Yield
With molecular sieve; potassium tert-butylate In tetrahydrofuran; benzene Heating;	81%
With molecular sieve; potassium tert-butylate In tetrahydrofuran; benzene Product distribution; Heating; also without molecuar sieves and reflux;	81%

N-nitro-15-pentadecanelactam (122695-16-3) → pentadecanolide (106-02-5)

Conditions	Yield
In tetrachloromethane for 12h; Heating;	80%

methyl 15-hydroxypentadecanoate (76529-42-5) → pentadecanolide (106-02-5) + 1,17-dioxa-cyclodotriacontane-2,18-dione (659-76-7)

Conditions	Yield
In benzene at 40℃; for 72h; Lipase P;	A 78% B n/a
With Lipase P In benzene at 40℃; for 72h; Product distribution;

15-hydroxylpentadecanoic acid (4617-33-8) + 2-chloro-1-ethyl-3-methylpyridinium tetrafluoroborate → pentadecanolide (106-02-5)

Conditions	Yield
With triethylamine In acetonitrile	78%

methanol (67-56-1) + pentadecanolide (106-02-5) → methyl 15-hydroxypentadecanoate (76529-42-5)

Conditions	Yield
With sulfuric acid Reflux;	100%
With sulfuric acid Reflux;	100%
With toluene-4-sulfonic acid for 24h; Esterification; Ring cleavage; Heating;	99%

pentadecanolide (106-02-5) → 15-hydroxylpentadecanoic acid (4617-33-8)

Conditions	Yield
With (Z)-9-octadecen-1-amine; lipase PS from Pseudomonas cepacia; water In Hexadecane at 40℃; for 0.5h; Miniemulsion system; Enzymatic reaction;	100%
With sodium hydroxide In tetrahydrofuran; methanol; water	100%
With potassium hydroxide In methanol; water for 5.5h; Heating;	99%

pentadecanolide (106-02-5) → 15-iodo-pentadecanoic acid (71736-22-6)

Conditions	Yield
With hydrogen iodide In acetic acid for 3h; Ring cleavage; iodination; Heating;	100%
With aluminium(III) iodide In acetonitrile at 80℃; for 18h;	99%
With hydrogen iodide In acetic acid for 6h; Heating;	93%

pentadecanolide (106-02-5) → potassium 15-hydroxypentadecanoate (871570-58-0)

Conditions	Yield
With ethanol; potassium hydroxide for 2h; Reflux;	100%
With potassium hydroxide In ethanol for 2h; Reflux;	100%
With potassium hydroxide In ethanol for 2h; Reflux;	100%
With potassium hydroxide In methanol

pentadecanolide (106-02-5) + sodium methylate (124-41-4) → methyl 15-hydroxypentadecanoate (76529-42-5)

Conditions	Yield
In methanol at 20℃; for 16h; Inert atmosphere; Darkness;	99%
In methanol at 20℃;	80%

pentadecanolide (106-02-5) → 1,15-pentadecanediol (14722-40-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 72h;	98.6%
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 4h; Inert atmosphere;	97%
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 4h; Inert atmosphere;	96%

pentadecanolide (106-02-5) → 15-bromo-pentadecanoic acid (56523-59-2)

Conditions	Yield
With sulfuric acid; hydrogen bromide for 84h; Heating;	98%
With hydrogen bromide; acetic acid at 60℃; for 16h; Product distribution / selectivity; Autoclave; Inert atmosphere;	91%
With sulfuric acid; hydrogen bromide for 20h; Heating;	84%

methanol (67-56-1) + pentadecanolide (106-02-5) + sodium methylate (124-41-4) → methyl 15-hydroxypentadecanoate (76529-42-5)

Conditions	Yield
for 3h; Heating / reflux;	98%

pentadecanolide (106-02-5) + methylmagnesium bromide (75-16-1) → 15-methylhexadecan-1,15-diol (728935-75-9)

Conditions	Yield
Stage #1: pentadecanolide; methylmagnesium bromide In tetrahydrofuran at -78 - 20℃; for 16h; Inert atmosphere; Stage #2: With acetic acid In tetrahydrofuran; water Cooling with ice;	98%

indole (120-72-9) + pentadecanolide (106-02-5) → ω-(3-indolyl)pentadecanoic acid (74022-43-8)

Conditions	Yield
With sodium hydroxide at 250℃; for 18h; Product distribution; autoclave, other base, other temperature;	95%

pentadecanolide (106-02-5) + chlorophosphoric acid diphenyl ester (2524-64-3) → Phosphoric acid (E)-(oxacyclohexadec-2-en-2-yl) ester diphenyl ester

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.5h;	91%

pentadecanolide (106-02-5) + n-Octylamine (111-86-4) → N-octyl-15-hydroxypentadecanoylamine (1220909-19-2)

Conditions	Yield
With lipase PS from Pseudomonas cepacia; water In Hexadecane at 40℃; for 192h; Miniemulsion system; Enzymatic reaction;	91%

Upstream product

• 502-72-7 cyclopentadecanone 
• 56523-59-2 15-bromo-pentadecanoic acid 
• 121942-41-4 15-(tert-Butyl-dimethyl-silanyloxy)-pentadecanoic acid methyl ester 
• 4617-33-8 15-hydroxylpentadecanoic acid 
• 67-63-0 isopropyl alcohol 
• 173790-14-2 Z-oxacyclohexadec-3-en-2-one 
• 174390-08-0 1-hydroperoxy-16-oxabicyclo[10.4.0]hexadecane 
• 98-11-3 benzenesulfonic acid 
• 71-43-2 benzene 
• 57395-52-5 12-iodo-1-dodecanol 
• 71736-22-6 15-iodo-pentadecanoic acid 
• 112405-41-1 12-(N,N-Dimethylaminomethyl)-15-pentadecanolid-N-oxide 
• 78350-13-7 15-methoxypentadecanoic acid 
• 13362-52-2 1,13-tridecanediol 

Downstream Products

• 918876-31-0 2-(14-(benzyloxy)tetradecyl)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-6-yl acetate 
• 918876-27-4 2-(14-(benzyloxy)tetradecyl)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-6-ol 
• 918876-35-4 2-(14-(benzyloxy)tetradecyl)-6-methoxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene 
• 918876-24-1 17-(benzyloxy)-3-methylheptadec-1-en-3-ol 
• 76529-42-5 methyl 15-hydroxypentadecanoate 
• 175358-58-4 3-Phenylselanyl-oxacyclohexadecan-2-one 
• 4617-33-8 15-hydroxylpentadecanoic acid 
• 146964-66-1 2-Diphenylphosphinoyl-17-hydroxyheptadecan-3-one 
• 18270-60-5 15-hydroxy-pentadecanoic acid hydrazide 
• 14722-40-8 1,15-pentadecanediol 

Relevant articles and documents

A Short Synthesis of 15-Pentadecanolide

15-Pentadecanolide was synthesised by a five step, two pot reaction sequence, starting from 2-nitrocyclododecanone in a 60percent overall yield.

A THREE STEP SYNTHESIS OF EXALTOLIDE AND PHORACANTHOLIDE I

The synthesis of phoracantholide I and exaltolide are described in 3 steps and in good yields.

Macrolactonization of hydroxy acids using a polymer bound carbodiimide

An efficient macrolactonization procedure using a polymer bound carbodiimide is described. The procedure uses the polymer supported reagent as a replacement for dicyclohexylcarbodiimide and thus considerably simplifies the workup for such reactions. Partitioning between macrolactone and diolide is shown to depend upon the equivalents of reagent used in cases for which lactonization is difficult. (C) 2000 Published by Elsevier Science Ltd.

Lack of a "Cesium Effect" on Macrolactonization

The lactonization of ω-bromoalkanoate ions, run in DMF under preparative conditions and in the presence of counterions, is exploited to show that those synthetic effects whose manifestations has led to the coinage of the term "cesium effect" are simply due to the operation of well-established, rate-decreasing ion-pairing phenomena upon the reactivity of anionic nucleophiles.No peculiarity emerges with cesium when compared with the other alkali-metal ions.

Synthesis of ω-hydroxy carboxylic acids and α,ωdimethyl ketones using α,ω-diols as alkylating agents

"Chemical equation presented" Synthesis of ω-hydroxy carboxylic acids and α,ω-dimethyl diketones was successfully achieved by using α,ω-diols as alkylating agents under the influence of an iridium catalyst. For example, the alkylation of butyl cyanoacetate with 1,13-tridecanediol in the presence of [IrCl(cod)]2 or [rrCl(coe) 2]2 gave rise to butyl 2-cyano-15-hydroxypentadecanoate in good yield which is easily converted to cyclopentadecanolide (CPDL). In addition, the alkylation of acetone with 1,10-decanediol in the presence of [IrCl(cod)]2 and KOH resulted in an important muscone precursor, 2,15-hexadecanedione (HDDO), in good yield.

Tin(IV)-catalyzed lactonization of ω-hydroxy trifluoroethyl esters

1,1,1-Trifluoroethyl esters of ω-hydroxycarboxylic acids were prepared and their conversion to macrocyclic lactones, including ricinelaidic lactone, was studied in the presence of catalytic quantities of tin(IV) reagents; a mechanism involving exchange of alkoxytrialkyltin species is proposed.

Cyanuric chloride, a useful reagent for macrocyclic lactonization

Six ω-hydroxy acids have been converted to macrocyclic lactones by treatment with cyanuric chloride and triethylamine in acetone at room temperature. The mechanism apparently involves activation of both the carboxyl and hydroxyl groups.

A Simple Method for the Synthesis of Exaltolide

Copper-catalyzed reaction of β-propiolactone with 12-methoxydodecylmagnesium bromide, derived from 1,12-dodecanediol, gives 15-methoxypentadecanoic acid in a high yield, which is easily converted into exaltolide.

A novel and efficient macrolactonization of ω-hydroxycarboxylic acids using 2-methyl-6-nitrobenzoic anhydride (MNBA)

A variety of lactones were prepared in high yields at room temperature from the corresponding ω-hydroxycarboxylic acids using 2-methyl-6-nitrobenzoic anhydride in the presence of 4-(dimethylamino)pyridine. A similar reaction also occurs with triethylamine when using a catalytic amount of 4-(dimethylamino)pyridine 1-oxide as an effective promoter for the intramolecular condensation reaction. These methods were successfully applied to the synthesis of erythro-aleuritic acid lactone and the efficiency of the cyclizations is compared to those of other reported mixed anhydride methods.

An acid-catalyzed macrolactonization protocol.

[reaction: see text] An efficient macrolactonization protocol devoid of any base was developed derived from the use of vinyl esters in transesterification. Subjecting a hydroxy acid and ethoxyacetylene to 2 mol % [RuCl(2)(p-cymene)](2) in toluene followed by addition of camphorsulfonic acid or inverse addition provided macrolactones in good yields.