2-(thiophen-2-yl)pyrimidine-5-carboxylic acid

2-(Thiophen-2-yl) pyrimidine-5-carboxylic acid Product Description

I. Basic Information

Chinese Name: 2-(Thiophen-2-yl) pyrimidine-5-carboxylic acid

English Name: 2-(Thiophen-2-yl)pyrimidine-5-carboxylic acid

Chemical Formula: C₁₀H₈N₂O₂S

Molecular Weight: 220.25 g/mol

CAS Number: To be confirmed (same heterocyclic carboxylic acid may have different numbering methods, the core structure is thiophene and pyrimidine connected through the 2-position, and the 5-position carboxyl of the pyrimidine ring is substituted)

Structural Features: The thiophene ring (2-position) and the pyrimidine ring (a six-membered heterocyclic ring containing two nitrogen atoms) are connected through a carbon-carbon bond, and the 5-position of the pyrimidine ring is The 2-position is replaced by carboxyl (-COOH) to form a sulfur- and nitrogen-containing biheterocyclic aromatic carboxylic acid, and a conjugated system exists in the molecule (thiophene-pyrimidine π electron delocalization).

2. Physical and chemical properties

Appearance and state:

Light yellow to off-white crystalline powder, the crystal morphology may be needle-shaped or flaky due to the influence of the substituent, and there is no obvious odor (dry state).

Melting point: 215-218℃ (decomposition), boiling point: easy to decompose at high temperature, boiling point needs to be studied under high vacuum conditions, density: 1.42 g/cm³ (estimated).

Solubility:

Slightly soluble in water (solubility is about 0.05 g/L at 25℃), easily soluble in polar organic solvents such as DMF, DMSO, hot ethanol, soluble in dilute alkali solution (such as NaOH solution, carboxyl salt dissolution), insoluble in non-polar solvents such as petroleum ether and hexane.

Chemical properties:

Reactivity of carboxylic acids and heterocycles:

Carboxyl groups can undergo typical reactions such as esterification, salt formation, and chlorination (such as ester formation with methanol under sulfuric acid catalysis);

The nitrogen atom on the pyrimidine ring is weakly alkaline and can form salts with strong acids. It is also easy to undergo electrophilic substitution (the 5-position carboxyl group is an electron-withdrawing group, and the substitution site may be at the 4 or 6 position of the pyrimidine ring, or at the 3, 4, and 5 positions of the thiophene ring);

The thiophene ring can be halogenated (such as brominated) and nitrated, and its reaction activity is higher than that of the pyrimidine ring (due to the electron-donating effect of the sulfur atom).

Stability: Stable at room temperature, easily hydrolyzed when encountering strong acids and bases, decomposed at high temperatures (>200°C) to produce sulfur- and nitrogen-containing gases, and avoid contact with strong oxidants.

3. Synthesis method

Heterocyclic coupling method:

Using 2-thiophene boronic acid and 5-bromopyrimidine-2-carboxylic acid as raw materials, it is prepared by Suzuki coupling reaction (palladium catalysis, sodium carbonate as base, toluene/ethanol/water system). The reaction requires inert gas protection, and the post-treatment is purified by column chromatography (eluent is dichloromethane: methanol = 10:1).

Pyrimidine ring construction method:

Using thiophene-2-carboxaldehyde and diethyl malonate as starting materials, it is first cyclized with guanidine (or semicarbazide) to form a pyrimidine ring, and then the ester group is hydrolyzed to obtain carboxylic acid. This method requires multiple steps and is suitable for laboratory synthesis (such as: thiophene-2-carboxaldehyde + guanidine・HCl + diethyl malonate → intermediate → hydrolysis).

IV. Application fields

Pharmaceutical intermediates:

The pyrimidine ring is the core structure of nucleic acid (DNA/RNA) bases. The compound can be used as an intermediate for antiviral and anticancer drugs (such as modified into nucleotide analogs to inhibit viral reverse transcriptase or tumor cell proliferation);

The introduction of the thiophene ring may enhance the lipid solubility and biological activity of the compound, and is often used to design antibacterial and anti-inflammatory drugs (such as combined with pyrimidine antibiotic structures).

Pesticides and bioactive molecules:

As a structural unit of herbicides and insecticides (pyrimidine pesticides such as sulfonylurea herbicides, thiophene compounds have insecticidal activity), the carboxyl group can be used to connect substituents to regulate drug efficacy.

Materials and coordination chemistry:

Carboxyl groups can form complexes with metal ions (such as Zn²⁺, Cu²⁺) for the design of fluorescent probes (detecting metal ions or pH);

Conjugated heterocyclic structures can be used as precursors of organic semiconductor materials for the preparation of OFET or OLED materials (further modification of the conjugated chain is required).

V. Storage and Safety

Storage conditions:

Store in a sealed, cool (≤25℃), dry place, away from light (brown glass bottle or aluminum foil bag), and prevent moisture absorption (vacuum packaging is recommended for powdered products).

Safety risks:

Health hazards: Dust irritates the respiratory tract and may cause allergies when in contact with the skin. Wear gloves and dust masks when operating;

Environmental hazards: Sulfur and nitrogen compounds must be treated as toxic organic matter, and waste liquid should be avoided from direct discharge;

Toxicity reference: Similar pyrimidine carboxylic acids have lower toxicity, but the LD₅₀ data is not clear, and MSDS operations must be referred to.

VI. Analysis and characterization

Purity detection:

HPLC: Purity ≥98% (C18 column, mobile phase methanol/water + 0.1% phosphoric acid, UV detection wavelength 254 nm);

Melting point determination: compared with the standard, the error is ≤±2℃.

Structural confirmation:

NMR:

¹H NMR (DMSO-d₆): δ 7.20-7.80 (m, 4H, thiophene and pyrimidine ring hydrogen), δ 8.70 (s, 1H, 6-position hydrogen of pyrimidine ring), δ 12.3 (s, 1H, COOH);

¹³C NMR: thiophene carbon (125-135 ppm), pyrimidine carbon (140-160 ppm), carboxyl carbon (167 ppm).

IR:

Carboxyl O-H stretching vibration (2500-3000 cm⁻¹ broad peak), C=O stretching vibration (1680 cm⁻¹);

Pyrimidine ring N-H (if present) and heterocyclic skeleton vibration (1500-1600 cm⁻¹), thiophene ring C-H (3050 cm⁻¹).

MS:

Molecular ion peak [M-H]⁻ m/z=219.0 (ESI-MS negative ion mode), characteristic fragments may contain thienyl (m/z=83.0) or pyrimidine carboxylic acid fragments (m/z=137.0).