80-59-1

Usage

Uses

Used in Perfume Manufacturing Industry:
Tiglic acid is used as a raw material to synthesize esters for the perfume manufacturing industry, contributing to the creation of various fragrances.
Used in Food and Beverage Industry:
Tiglic acid serves as a raw material to produce acids and esters that are applied as flavoring agents in the food and beverage industry, enhancing the taste and aroma of various products.
Used in Pharmaceutical Industry:
Tiglic acid is a useful starting material in the synthesis of pharmaceutical intermediates, playing a crucial role in the development of new medications and therapies.

References

[1] H. Panda (2010) Perfumes and Flavours Technology Handbook. [2] Paul T. Anastas (2009) Handbook of Green Chemistry, Green Catalysis, Biocatalysis. [3] https://en.wikipedia.org/wiki/Tiglic_acid

Air & Water Reactions

Slightly soluble in water.

Reactivity Profile

TIGLIC ACID is a carboxylic acid. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Carboxylic acids in aqueous solution and liquid or molten carboxylic acids can react with active metals to form gaseous hydrogen and a metal salt. Such reactions occur in principle for solid carboxylic acids as well, but are slow if the solid acid remains dry. Even "insoluble" carboxylic acids may absorb enough water from the air and dissolve sufficiently in Tiglic acid to corrode or dissolve iron, steel, and aluminum parts and containers. Carboxylic acids, like other acids, react with cyanide salts to generate gaseous hydrogen cyanide. The reaction is slower for dry, solid carboxylic acids. Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide. Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat. Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents. These reactions generate heat. A wide variety of products is possible. Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions.

Health Hazard

TOXIC; inhalation, ingestion or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.

Fire Hazard

Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes. Some are oxidizers and may ignite combustibles (wood, paper, oil, clothing, etc.). Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated.

Safety Profile

Low toxicity by ingestion and skin contact. A severe skin irritant. When heated to decomposition it emits acrid smoke and irritating fumes.

Synthesis

Synthesized from 2-hydroxy-2-methylbutyronitrile

Purification Methods

Crystallise it from water. It is steam volatile and is soluble in organic solvents. [Beilstein 2 IV 1552.]

InChI:InChI=1/C5H8O2/c1-3-4(2)5(6)7/h3H,1-2H3,(H,6,7)/b4-3-

Synthetic route

(S)-12-hydroxypentadecanoic acid 12-O-(6-O-(S)-2-methylbutyryl)-β-D-glucopyranosyl-(1->3)-O-[4-O-tigloyl-α-L-rhamnopyranosyl-(1->4)]-O-[2-O-(S)-2-methylbutyryl]-α-L-rhamnopyranosyl-(1->4)-O-α-L-rhamnopyranosyl-(1->2)-β-D-glucopyranoside (1400908-83-9) → 2-Methylbutanoic acid (116-53-0, 600-07-7) + Tiglic acid (80-59-1) + (S)-12-hydroxypentadecanoic acid 12-O-β-D-glucopyranosyl-(1->3)-O-[α-L-rhamnopyranosyl-(1->4)]-O-α-L-rhamnopyranosyl-(1->4)-O-α-L-rhamnopyranosyl-(1->2)-β-D-glucopyranoside (1400908-78-2)

Conditions	Yield
With potassium hydroxide at 85℃; for 4h; pH=4;	A 98% B 98% C 3 mg

turpethoside acid B (1400908-85-1) → 2-Methylbutanoic acid (116-53-0, 600-07-7) + Tiglic acid (80-59-1) + (S)-12-hydroxyhexadecanoic acid 12-O-β-D-glucopyranosyl-(1->3)-O-[α-L-rhamnopyranosyl-(1->4)]-O-α-L-rhamnopyranosyl-(1->4)-O-α-L-rhamnopyranosyl-(1->2)-β-D-glucopyranoside (1400908-79-3)

Conditions	Yield
With potassium hydroxide at 85℃; for 4h; pH=4;	A 98% B 98% C 3 mg

(E)-2-bromobut-2-ene (3017-71-8) + carbon monoxide (201230-82-2) → Tiglic acid (80-59-1)

Conditions	Yield
With sodium hydroxide; cetyltrimethylammonim bromide; nickel cyanide In toluene at 95℃; under 735.5 Torr; for 6h;	89%
With calcium hydroxide; methyl iodide; dicobalt octacarbonyl In 1,4-dioxane; water at 20℃; under 760 Torr; for 20h;	88 % Chromat.

dicobalt octacarbonyl (15226-74-1, 61091-28-9, 61117-58-6) + (E)-2-bromobut-2-ene (3017-71-8) → Tiglic acid (80-59-1)

Conditions	Yield
With calcium hydroxide; carbon monoxide; methyl iodide In 1,4-dioxane; water 20°C, 20 h.;	88%

dicobalt octacarbonyl (15226-74-1, 61091-28-9, 61117-58-6) + (Z)-2-Bromo-2-butene (3017-68-3) → Tiglic acid (80-59-1)

Conditions	Yield
With calcium hydroxide; carbon monoxide; methyl iodide In 1,4-dioxane; water 20°C, 20 h.;	87%

Cp2TiOOC(trans-C(CH3)=CHCH3) → Tiglic acid (80-59-1)

Conditions	Yield
With water In diethyl ether for 1h; Ambient temperature;	85%

(E)-3-methylpent-3-en-2-one (1567-73-3) → Tiglic acid (80-59-1)

Conditions	Yield
With sodium hypochlorite solution; sodium hydroxide at 55 - 60℃; for 1h; Large scale;	84.3%

2-hydroxy-2-methylbutyric acid (3739-30-8) → Tiglic acid (80-59-1)

Conditions	Yield
With sulfuric acid at 140℃;	76.5%
Erhitzen;
With sulfuric acid at 115 - 130℃; im geschlossenen Rohr;

2-chloro-2-methylbutyric acid (73758-54-0) → Tiglic acid (80-59-1)

Conditions	Yield
With potassium hydroxide In ethanol for 6h; Reflux;	70%

2-methylenebutyric acid (3586-58-1) → Tiglic acid (80-59-1)

Conditions	Yield
With water at 230℃; for 3h;	62%
With sulfuric acid

2-acetylpropanoic acid ethyl ester (609-14-3) → Tiglic acid (80-59-1)

Conditions	Yield
With methanol; calcium borate anschliessend mit methanol. Natronlauge und Erhitzen des nach dem Ansaeuern mit wss. Salzsaeure erhaltenen Reaktionsprodukts in Gegenwart von Toluol-4-sulfonsaeure;
Multi-step reaction with 2 steps 1: sodium amalgam; diluted alcohol / man haelt die Reaktion mit verduennter Schwefelsaeure stets schwach saurer 2: Destillation View Scheme

carbon disulfide (75-15-0) + Angelic acid (565-63-9) → Tiglic acid (80-59-1)

Conditions	Yield
bei Gegenwart von Spuren Brom;in dem direkten Sonnenlicht;

3-methyl-4,5-dihydro-3H-pyrazole-3-carboxylic acid ethyl ester → Tiglic acid (80-59-1) + 1-methylcyclopropanecarboxylic acid ethyl ester (71441-76-4)

Conditions	Yield
at 140℃;

2-methylbut-2-enal (497-03-0) → Tiglic acid (80-59-1)

Conditions	Yield
an der Luft;
Stage #1: 2-methylbut-2-enal With palladium(II) trifluoroacetate at 10℃; for 0.166667h; Stage #2: With dihydrogen peroxide In water at 10℃; chemoselective reaction;	47 %Chromat.

(E)-2-bromobut-2-ene (3017-71-8) → Tiglic acid (80-59-1)

Conditions	Yield
With tetrahydrofuran; magnesium anschliessend mit Kohlendioxid;
With diethyl ether; lithium anschliessend mit Kohlendioxid;

Angelic acid (565-63-9) → Tiglic acid (80-59-1)

Conditions	Yield
Kochen;
at 300℃; im geschlossenen Rohr;
With sulfuric acid at 100℃;

pent-2-enoic acid (626-98-2, 13991-37-2, 16666-42-5) → Tiglic acid (80-59-1) + butanone (78-93-3)

Conditions	Yield
With sulfuric acid

Upstream product

• 609-14-3 2-acetylpropanoic acid ethyl ester 
• 497-03-0 2-methylbut-2-enal 
• 3017-71-8 (E)-2-bromobut-2-ene 
• 565-63-9 Angelic acid 
• 626-98-2 pent-2-enoic acid 
• 3739-30-8 2-hydroxy-2-methylbutyric acid 
• 91114-65-7 2,3-dibromo-2-methylbutanoic acid 
• 3586-58-1 2-methylenebutyric acid 
• 4111-08-4 2-hydroxy-2-methyl-butyronitrile 
• 473-86-9 3-hydroxy-2-methylbutyric acid 
• 27372-03-8 ethyl 3-hydroxy-2-methylbutyrate 
• 90271-22-0 3-acetoxy-2-methyl-butyric acid 
• 108-24-7 acetic anhydride 
• 137-40-6 sodium proprionate 

Downstream Products

• 6622-76-0 methyl (E)-2-methyl-2-butenoate 
• 5837-78-5 Ethyl tiglate 
• 28127-58-4 sec-butyl tiglate 
• 61692-84-0 (E)-2-Methyl-2-butensaeureisobutylester 
• 116-53-0 2-Methylbutanoic acid 
• 565-63-9 Angelic acid 
• 35660-94-7 (E)-2-methylbut-2-enoyl chloride 
• 14868-24-7 2,3-dihydroxy-2-methylbutyric acid 
• 91114-65-7 2,3-dibromo-2-methylbutanoic acid 
• 95494-39-6 p-bromophenacyl tiglate 
• 5798-88-9 β-bromo-isovaleric acid 
• 7785-64-0 (E)-butyl 2-methylbut-2-enoate 
• 19731-91-0 α-methyl-β-phenylbutyric acid 
• 66052-32-2 methyl 2,5-dimethyl-2-vinylhex-4-enoate 

Relevant academic research and scientific papers

A secoiridoid and other constituents of Gonocaryum calleryanum

Investigation of the leaves, branch, stem and root bark of Gonocaryum calleryanum resulted in the isolation of a new secoiridoid glycoside, gonocaryoside E, together with 14 known compounds. Their structures were elucidated by spectral analysis and chemical transformation. Gonocaryoside E was shown to be a derivative of kingiside in which the lactone ring was open, and with the 8-hydroxy group esterified with tiglic acid. Alkaline hydrolysis of these secoiridoids is discussed.

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Six previously undescribed resin glycosides, calyhedins I–VI, were isolated from the rhizomes of Calystegia hederacea Wall., which are the first genuine resin glycosides isolated from C. hederacea. The structures of calyhedins I–VI were determined based on spectroscopic data and chemical evidence. All the compounds have macrolactone structures (jalapins), and their sugar moieties were partially acylated by five organic acids. Calyhedins I, II–V, and VI have 27-, 28-, and 23-membered rings, respectively, and calyhedins IV–VI are the first jalapins with a sugar chain consisting of seven monosaccharides. Additionally, the cytotoxic activity of calyhedins II and III toward HL-60 human promyelocytic leukemia cells was evaluated. Both compounds demonstrated almost the same activity as the positive control, cisplatin.

Method for simply and conveniently synthesizing tiglic acid

The invention discloses a method for simply and conveniently synthesizing tiglic acid. The method comprises the following steps: carrying out an addition reaction between a Grignard reagent and pyruvic acid or alpha-butanone acid at a normal temperature by using HMPA or DMPU as an assistant to obtain 2-hydroxy-2-methylbutyric acid, marking the 2-hydroxy-2-methylbutyric acid as an intermediate III;and then, heating the intermediate III under the action of sulfuric acid with a mass concentration of not less than 67% to carry out dehydration reaction to obtain tiglic acid. Materials which can cause serious pollution in the prior art are not used, the reaction steps are short, the technological conditions are simple, no special requirements for equipment exist, the product yield is high, andthe method is suitable for industrial production.

Sodium Methyl Carbonate as an Effective C1 Synthon. Synthesis of Carboxylic Acids, Benzophenones, and Unsymmetrical Ketones

Reported is the synthesis of carboxylic acids, symmetrical ketones, and unsymmetrical ketones with selectivity achieved by exploiting the differential reactivity of sodium methyl carbonate with Grignard and organolithium reagents.

Industrial preparation method of tiglic acid

The invention discloses an industrial preparation method of tiglic acid. The industrial preparation method is characterized by comprising the following steps: taking sodium acid sulfate as a catalyst,preparing 3-methyl-3-pentene-2-one (formula II) by utilizing paraldehyde and butanone which are cheap and are commercially easily obtained, and carrying out haloform reaction on a compound shown as the formula II, a sodium hypochlorite water solution and a sodium hydroxide water solution in a continuous flowing reactor to prepare the tiglic acid (formula I). By adopting the method, the disadvantages in the prior art are overcome; the method has the advantages that a utilized catalyst is cheap and easy to obtain and has high catalytic activity, no corrosion to equipment and less pollution caused by three wastes; the continuous flowing reactor provides better heat efficiency and has lower energy consumption; meanwhile, compared with a kettle type stirring reactor, production procedures aresimplified, the production time is shortened, the yield of a product is high and the operation is simple; the method is more suitable for industrial production.

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Resin Glycosides from Ipomoea alba Seeds as Potential Chemosensitizers in Breast Carcinoma Cells

Multidrug resistance is the expression of one or more efflux pumps, such as P-glycoprotein, and is a major obstacle in cancer therapy. The use of new potent and noncytotoxic efflux pump modulators, coadministered with antineoplastic agents, is an alternative approach for increasing the success rate of therapy regimes with different drug combinations. This report describes the isolation and structure elucidation of six new resin glycosides from moon vine seeds (Ipomoea alba) as potential mammalian multidrug-resistance-modifying agents. Albinosides IV-IX (1-6), along with the known albinosides I-III (7-9), were purified from the CHCl3-soluble extract. Degradative chemical reactions in combination with NMR spectroscopy and mass spectrometry were used for their structural elucidation. Four new glycosidic acids, albinosinic acids D-G (10-13), were released by saponification of natural products 3-6. They were characterized as tetrasaccharides of either convolvulinolic (11S-hydroxytetradecanoic) or jalapinolic (11S-hydroxyhexadecanoic) acids. The potentiation of vinblastine susceptibility in multidrug-resistant human breast carcinoma cells of albinosides 1-6 was evaluated by modulation assays. The noncytotoxic albinosides VII (4) and VIII (5), at a concentration of 25 μg/mL, exerted the strongest potentiation of vinblastine susceptibility, with a reversal factor (RFMCF-7/Vin+) of 201- and >2517-fold, respectively.

Three acylated glycosidic acid methyl esters and two acylated methyl glycosides generated from the convolvulin fraction of seeds of Quamoclit pennata by treatment with indium(III) chloride in methanol

Treatment of the ether-insoluble resin glycoside (convolvulin) fraction from seedsof Quamoclit pennata (Convolvulaceae) with indium(III) chloride in methanol provided three oligoglycosides of hydroxy fatty acid (glycosidic acid) methyl esters and two methyl glycosides, which were partially acylated by a glycosidic acid, 75-hydroxydecanoic acid 7-0-β-d-quinovopyranoside (quamoclinic acid B) and/or two organic acids, (E)-2-methylbut-2-enoic (tiglic) acid and/or 3R-hydroxy-2R-methylbutyric (nilic) acid. Theirstructures were elucidated on the basis of spectroscopic data and chemical conversions.

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Three glycosidic acids, turpethic acids A-C, and two intact resin glycosides, turpethosides A and B, all having a common pentasaccharide moiety and 12-hydroxy fatty acid aglycones of different chain lengths, were obtained from the aerial parts of Operculina turpethum. Their structures were elucidated by spectroscopic analyses and chemical correlations. The aglycones were characterized as 12-hydroxypentadecanoic acid in two compounds, 12-hydroxyhexadecanoic acid in two other components, and 12-hydroxyheptadecanoic acid in the fifth compound, which were all confirmed by synthesis. The absolute configurations of these aglycones were all established as S by Mosher's method. These compounds represent the first examples of resin glycosides with a monohydroxylated 12-hydroxy fatty acid as an aglycone, and one compound is the first described resin glycoside having a hydroxylated C17 fatty acid as its aglycone.