CN106632395A - Spiro-amino acid ester compound, and preparation method and application thereof - Google Patents

Abstract

The invention relates to a spirocyclic amino acid ester compound, a preparation method and application thereof. The technical scheme adopted in the present invention is: a spirocyclic amino acid ester compound having a structural formula of formula (I). The preparation method is as follows: use benzylamine, carbonate and tetrabromopentaerythyl alcohol as raw materials, condense and reflux at 130-150°C in a polar solvent to obtain the target product. In the present invention, benzylamine, potassium carbonate and tetrabromopentaerythyl alcohol are used as raw materials, and the target product can be obtained through a one-pot reaction. This compound has both a spiro ring structure and an amino acid ester group, and is a novel The spirocyclic amino acid ester compound of the present invention has simple operation, relatively short production cycle and easy purification, and is expected to be widely used in industry, agriculture and medicine.

Description

A kind of spirocyclic amino acid ester compound and its preparation method and application

technical field

The invention belongs to the field of organic chemical synthesis, and in particular relates to a spirocyclic amino acid ester compound and a preparation method thereof.

Background technique

A polycyclic compound in which two monocyclic rings share one carbon atom is called a spirocyclic compound, and the shared carbon atom is called a spiro atom. There are many methods for synthesizing spiro compounds. The synthesis of simple spiro compounds usually adopts 1,3-dipolar cycloaddition reaction, ketal method, malonate and pentaerythroxybromide (chlorine) reaction, acid anhydride and double Grignard Reactions of reagents, etc. Spiral compounds have a rigid and stable structure, especially chiral spiro compounds have a large specific rotation, and have important applications in asymmetric catalysis, medicine, luminescent materials, and pesticides. For example, Srivastava and Kumar reported that lithium aluminum tetrahydride was modified with optically active spiro[4.4]nonane-1,6-diol for the equivalent reduction of aromatic ketones, and the ee value was as high as 98%, which fully demonstrated the excellent spirocyclic skeleton. asymmetric induction effect. Goekjian et al. prepared spiroglucose derivatives by reacting methylene glucose derivatives with aromatic nitrile oxides. Such compounds can be used as antibodies to glucosylphosphosides. In 2007, Tominaga et al. synthesized a series of spiro-ring structure compounds, and found that the relative molecular mass of such substances was greater than 600, and the melting point was higher than 150°C, which had better thermal stability and photochromic properties. Baker et al. found that the gonad secretions of sexually mature female Drosophila contained spiroketal compounds. In addition, spiroketals also existed in the male glands of Drosophila. Spiral ketals not only exist as sex pheromone components in many Drosophila glands, but also exist as structural units in many complex natural products with strong physiological activities, such as the antibiotic Okadaic acid and the potent anticancer substance Spongistatin. Contains spiro ketal structural units. In 1979, NunzioR et al. prepared spiro[1-cyclopropyl-1'-indenyl]-2-formic acid-α-cyano-3,3-dimethyl (3-phenoxybenzyl) ester, the compound Mixed with PVC, it has obvious anti-mite effect and has low toxicity to mammals.

For the synthesis of amino acid esters, acid catalysis, transesterification, triphosgene and the like are usually used. Amino acid ester compounds have special physical and chemical properties, and are widely used in chemical industry, medicine, pesticide and other fields. Sun Jianjun and others used glutamic acid and lauryl alcohol as raw materials, and used solid superacid ZrO ₂ -SO ₄ ^2- as a catalyst to synthesize lauryl glutamate surfactant; Zeng Yiliang et al. screened out an N-methylalkyl substituted benzene An amino carbamate compound, which has excellent efficacy in controlling a variety of aphids, has low toxicity to mammals, is safe to use, has readily available raw materials, and is low in cost; B. Ramamurthy reported that amino acid ester derivatives have anti-tuberculosis activity. However, there are few reports on compounds with both spiro rings and amino acid ester groups, especially the target product: double amino acid ester groups with spiro rings, which has not been reported so far.

Contents of the invention

The purpose of the present invention is to provide a simple method, and a novel spiro amino acid ester compound having both a spiro ring structure and an amino acid ester group can be obtained through a one-pot reaction.

In order to achieve the above object, the technical solution adopted in the present invention is: a spirocyclic amino acid ester compound having the structural formula of formula (I):

The preparation method of the above-mentioned spirocyclic amino acid ester compound is as follows: use benzylamine, carbonate and tetrabromopentaerythyl alcohol as raw materials, condense and reflux at 130-150° C. in a polar solvent to obtain the target product.

In the preparation method of the above-mentioned spirocyclic amino acid ester compound, the polar solvent is DMF.

In the preparation method of the above-mentioned spirocyclic amino acid ester compound, the carbonate is potassium carbonate.

The preparation method of the above-mentioned spirocyclic amino acid ester compound, according to the molar ratio of feeding, benzylamine:carbonate:tetrabromopentaerythyl alcohol=4:1.5:2.

The preparation method of the above-mentioned spirocyclic amino acid ester compound is condensed and refluxed for 12-16 hours.

The beneficial effects of the present invention are:

1. The present invention uses benzylamine, salt of wormwood and tetrabromopentaerythyl alcohol as raw materials, and through a one-pot reaction, the target product can be obtained. This compound not only has a spiro ring structure but also contains an amino acid ester group, and is a A novel spirocyclic amino acid ester compound.

2. The spirocyclic amino acid ester compound synthesized by the present invention is a compound containing 1-oxygen-3-nitrogen-2-ketone structural unit. This structural compound has a wide range of biological activities and is used as an intermediate for synthesizing active drugs. Active drugs can be used to treat Alzheimer's disease.

3. The spirocyclic amino acid ester compound synthesized by the present invention is a compound containing 1-oxygen-3-nitrogen-2-ketone structural unit, and this structural compound is widely used as a herbicide for various crops, not only has a significant herbicidal effect, And it has good crop weed selectivity, especially for rice weed control.

4. The synthetic spirocyclic amino acid ester compound of the present invention is the compound containing 1-oxygen-3-nitrogen-2-ketone structural unit, and this structural compound is the inhibitor of 11-beta-hydroxysteroid dehydrogenase 1, with For the treatment of metabolic diseases such as metabolic syndrome, diabetes, obesity and dyslipidemia.

5. The method of the present invention is simple to operate, relatively short in production cycle, easy to purify, and is expected to be widely used in industry, agriculture, and medicine.

Description of drawings

Figure 1 is the MS (CH ₂ Cl ₂ ) chart of the target product prepared in the example.

Fig. 2 is the ¹ HNMR (CDCl ₃ ) chart of the target product prepared in the example.

Fig. 3 is the IR (KBr) figure of the target product prepared in the embodiment.

Fig. 4 is a single crystal thermal ellipsoid diagram of the target product prepared in the embodiment.

detailed description

In order to better understand the present invention, the present invention will be further described below through examples.

Example

(1) Preparation method:

Add 0.776g (2mmol) tetrabromopentaerythyl alcohol, 0.429g (4mmol) benzylamine, 0.207g (1.5mmol) potassium carbonate and 10ml of DMF to a 100ml three-necked flask, and reflux at 140° for 12h. After the reaction, the inorganic salt was filtered off, and DMF was distilled off under reduced pressure. Add absolute ethanol and crystallize to obtain 0.099 g of white needle crystals.

(2) Results

1. The melting point of the product is 190-191°C.

2. Figure 1 is the MS (CH ₂ Cl ₂ ) chart of the target product. As shown in Figure 1, the ESI-MS of the target product: Calculated M: 366.4 Found[M+Na] ⁺ : 389.3.

3. Figure 2 is the ¹ HNMR (CDCl ₃ ) figure of the target product, as can be seen from Figure 2, ¹ H NMR (CDCl ₃ , 300MHz) δ: 2.96 (2H, d, CH ₂ ), 3.10 (2H, d, CH ₂ ), 3.97 (2H, d, CH ₂ ), 4.09 (2H, d, CH ₂ ), 4.44 (4H, t, CH ₂ ), 7.35 (10H, m, Ar-H).

4. Figure 3 is the IR (KBr) diagram of the target product, as can be seen from Figure 3, IR (KBr), λmax/cm ^-1 : 3367.59cm ^-1 , 3032.67cm ^-1 , 2921.28cm ^-1 , 1689.59cm ^-1 , 1492.44cm ^-1 , 1437.25cm ^-1 , 1369.44cm ^-1 , 1266.93cm ^-1 , 1229.08cm ^-1 , 1184.92cm -1 , 1095.02cm ^-1 , 1031.94cm ^-1 , 749.64cm ^{-1 ,} 713.37cm ^-1 , 694.45cm ^-1 .

5. Figure 4 is the single crystal thermal ellipsoid diagram of the target product. The structural analysis of the target product is as follows: the crystal belongs to the monoclinic system, the Cc space group, and the unit cell parameters are, β=96.157(5)°. Z=4, the experimental formula is C ₂₀ H ₂₀ NO ₂ , the relative molecular mass is 306.37, and the calculated crystal density is Dc=1.110g/cm ^-3 . The main bond length and bond angle are: ∠O2-C6-N1=119.60°, ∠C6-N1-C3=123.97°, ∠C6-O2-C2=118.78°. ∠C4-N2-C7=123.55°, ∠N2-C7-O4=119.73°, ∠C7-O4-C5=120.30°.

Claims (6)

1. A spirocyclic amino acid ester compound is characterized in that it has the structural formula of formula (I): 2. the preparation method of spirocyclic amino acid ester compound described in claim 1 is characterized in that: method is as follows: take benzylamine, carbonate, tetrabromopentaerythyl alcohol as raw material, in polar solvent, 130-150 It was condensed and refluxed at °C to obtain the target product. 3. the preparation method of spirocyclic amino acid ester compound as claimed in claim 2 is characterized in that: described polar solvent is DMF. 4. the preparation method of spirocyclic amino acid ester compound as claimed in claim 2 is characterized in that: described carbonate is potassium carbonate. 5. the preparation method of spirocyclic amino acid ester compound as claimed in claim 2, is characterized in that: by feeding molar ratio, benzylamine: carbonate: tetrabromopentaerythyl alcohol=4:1.5:2. 6. the preparation method of spirocyclic amino acid ester compound as claimed in claim 2 is characterized in that: reflux 12-16 hour by condensation.