Study on the Reaction of α-enoyldithioketal with Diethyl Malonate

Abstract:  α- oxo ketene dithioacetals are flexible intermediates in natural blend having numerous functionalgroups that can build many mixtures with unique designs. The response of α-oxo ketene dithioacetals with diethyl malonate and the impact of substituents on the not entirely settled. The resultant item was a ring-opening formed triene compound with n-butyl as the subbed group.

Keywords：α-alkenoyl ketene-（S，S）-acetals；Diethyl malonate；Conjugated triene

0 preface:
α-Carbonyl disulfide ketals are a class of synthetic intermediates broadly utilized in the change between utilitarian gatherings of natural mixtures. They have a place with 1,3-dielectrophiles in structure, in which the carbonyl gathering should be visible As a hard electrophilic focus, the β-position can be viewed as a gentler electrophilic focus. By picking reasonable delicate and hard nucleophiles, such mixtures can specifically go through 1,2-or 1,4-formation expansion responses. The guideline of sulfur group makes α-carbonyldithioketal intensifies broadly utilized in the development of carbocyclic, heterocyclic and non-cyclic frameworks.
As per writing reports the alkylthio group impacts the response result of diethyl malonate and α-alkenoyl dithioketal. If the alkylthio group is an ethylthio group, the item is a polysubstituted form Triene compounds (Fig. 1a). When the alkylthio group is a butylthio group, the subsequent cyclohexenones can’t go through a ring-opening response (Fig. 1b). Since the reactant α-enoyl dithioketal is just In this way, it is important to concentrate on the impact of the alkylthio group in the design of α-enoyl dithioketal on the reaction product.

Figure 1 The different structures of products

1. Experimental part:

General technique: Varian As-500MHz atomic attractive reverberation contraption (inner standard TMS, dissolvable CDCl3 and DMSO-d6), Aglient 1200 series LC Mass, XT-5 miniature liquefying point analyzer, the temperature was not amended before use. The solvents utilized were all It is financially accessible scientifically unadulterated, with next to no other treatment, and α-alkenoyl dithioketal was synthesized by writing.

1. Experimental method:

Synthesis of α-alkenoyl dithioketal 3: Taking compound 3a for instance, take 2.009 g (5.4 mmol) of compound 2a into a round-lined carafe, add 50 mL of DMSO to disintegrate, and afterward drop 0.62 mL ( 6.0 mmol) p-methylbenzaldehyde, mix at room temperature, add 0.722 g (30.1 mmol) of sodium hydride strong in clumps. TLC monitors the disappearance of the substrate, pour the reaction mixture into saturated brine containing crushed ice, and stir well, ethyl acetate. The ester was separated multiple times, and the natural stages were joined. The ester layer was dried with anhydrous MgSO4, the dissolvable was dissipated under diminished pressure, and isolated by section chromatography (petrol ether:ethyl acetate=20:1) to get 0.629 g of a yellow strong with a yield of 31.3%. 

Synthesis of conjugated trienes 4: Take the blend of compound 4a for instance, add α-enoyl dithioketal 3a 0.513 g (1.08 mmol), DMF 6.78 mL, anhydrous potassium carbonate to a round base jar 0.141 g (1.02 mmol), and afterward 0.17 mL (1.11 mmol) of diethyl malonate was added. The response framework was blended at room temperature, and the response was observed by TCL. After the substrate vanished, the response arrangement was filled immersed saline and blended well. It was removed with ethyl acetic acid derivation multiple times, and the natural stages were consolidated. The ester layer was dried with anhydrous MgSO4 the dissolvable was vanished under decreased pressure, and isolated by section chromatography (petrol ether:ethyl acetate=10:1) to get a yellow semi-strong 0.252 g in a yield of 0.252 g. 41.9%. Compound 5 was combined similarly as formed triene compound 4, and a light yellow strong was obtained.

2. Compound Characterization:

3a：yellow solid，mp.136~138oC.1H NMR(CDCl3，500 MHz)：δ 8.48(s，1H)，7.63(d，1H，J=16.0 Hz)，7.55~ 7.57(m，2H)，7.44~7.46(m，2H)，7.25~7.27(m，2H)，7.19~7.20(m，2H)，7.02(d，1H，J=16.0 Hz)，2.92(t，4H， J=7.5 Hz)，2.38 (s，3H)，1.57~1.63 (m，4H)，0.87 (t，6H，J=7.5 Hz). 13C NMR (CDCl3，125 MHz) δ 13.55， 21.62, 31.73，35.12，121.03，125.79，128.54，128.91，129.21，129.65，131.78，136.26，138.38，141.13，144.25， 153.31，161.26，192.67. MS(m/z)：474.2[(M+H)]+.

3b：light yellow solid, mp. 147~149 oC.1H NMR(CDCl3，500 MHz)：δ 8.46(s，1H)，7.62(d，1H，J=16.0 Hz)， 7.54~7.56(m，2H)，7.45~7.48(m，2H)，7.27~7.29(m，2H)，7.20~7.22(m，2H)，7.00(d，1H，J=16.0 Hz)，2.93 (t，4H，J=7.5 Hz)，2.38(s，3H)，1.57~1.63(m，4H)，1.36~1.40(m，4H)，0.88(t，6H，J=7.5 Hz). 13C NMR (CD- Cl3，125 MHz) δ 13.53，21.51，21.91，31.74，35.10，121.00，125.77，128.55，128.89，129.15，129.71，131.67， 136.40，138.40，141.39，144.33，153.12，161.15，192.63. MS(m/z)：502.2[(M+H)]+.

3c：yellow solid, mp. 163~165oC.1H NMR (CDCl3，500 MHz)： δ 8.47 (s，1H)，7.64 (d，1H，J=16.0 Hz)， 7.53~7.56(m，2H)，7.42~7.45(m，2H)，7.25~7.29(m，2H)，7.17~7.20(m，2H)，7.01(d，1H，J=16.0 Hz)，2.99 (t，4H，J=7.5 Hz)，2.37(s，3H)，1.53~1.57(m，4H)，1.33~1.40(m，8H)，0.90(t，6H，J=7.5 Hz). 13C NMR(CD- Cl3，125 MHz) δ 13.57，21.52，21.94，30.46，31.73，35.12，121.04，125.79，128.54，128.88，129.11，129.73， 131.72，136.43，138.56，141.43，144.37，153.17，161.11，192.68. MS(m/z)：530.2[(M+H)]+.

4a：yellow solid, mp 173~175oC.1H NMR (500 MHz，CDCl3 ): δ14.71 (s，1H)，12.84 (br，1H)，7.48 (d，1H， J = 15.0 Hz)，7.41~7.44 (m，2H)，7.33~7.36 (m，2H)，7.22~7.25 (m，2H)，6.90~6.92 (m，2H)，6.58 (d，1H，J = 15.0 Hz)，4.31 (q，2H，J= 7.5 Hz)，4.17(q，2H，J= 7.5Hz)，2.74 (t，2H，J= 9.0 Hz)，2.39 (s，3H)，1.73 (m，2H)，1.37 (t，3H，J = 7.5 Hz)，1.26 (t，3H，J = 7.5 Hz)，1.13 (t，3H，J = 9.0 Hz).13C NMR (CDCl3，125 MHz) δ 13.3，13.4，14.2，21.4，25.5，26.2，61.5，61.7，99.3，118.2，122.5，127.8，129.1，129.3，129.5，130.3， 132.6，135.2，139.6，140.3，154.5，163.3，164.4，167.6，168.7. MS(m/z)：558.2[(M+H)]+

4b：yellow solid，mp 182~184oC.1H NMR (500 MHz，CDCl3 ):  δ14.68 (s，1H)，12.71 (br，1H)，7.53 (d，1H， J = 15.0 Hz)，7.47~7.51 (m，2H)，7.42~7.44 (m，2H)，7.34~7.37 (m，2H)，7.21~7.23 (m，2H)，6.85~6.87 (m，2H)，6.55 (d，1H，J = 15.0 Hz)，4.33 (q，2H，J= 7.5 Hz)，4.24 (q，2H，J= 7.5 Hz)，2.73 (t，2H，J= 7.5Hz)，2.43 (s，3H)，1.76~1.79(m，6H)，1.37 (t，3H，J= 7.5 Hz)，1.26 (t，3H，J= 7.5 Hz)，1.13 (t，3H，J= 7.5 Hz).13C NMR (CDCl3，125 MHz) δ 13.1，13.5，14.2，21.6，25.7，26.2，31.2，32.3，61.6，61.8，99.4，118.1， 122.3，127.7，129.2，129.4，129.7，130.5，132.7，135.5，139.8，140.1，154.3，163.2，164.3，167.3，168.6. MS(m/ z)：586.2[(M+H)]+.

5a：light yellow semi-solid，1H NMR(CDCl3，500 MHz)： δ 8.90(s，1H)，7.61(d，2H，J=9 Hz)，7.31(d，2H，J=9 Hz)，7.07~7.11(m，4H)，4.25(q，2H，J=7.5 Hz)，4.15~4.19(m，1H)，4.11(q，2H，J=7.5 Hz)，3.17~3.20(m， 1H)，2.99~3.03(m，1H)，2.83~2.91 (m，2H)，2.32 (s，3H)，1.50~1.54(m，2H)，1.29~1.32(m，2H)，1.25(t， 3H，J=7.5 Hz)，1.17(t，3H，J=7.5 Hz)，0.83(t，3H，J=7.5 Hz). MS(m/z)：572.2[(M+H)]+.

2 Results and discussion:

The preparation time and yield of compound 3 are shown in Table 1.

Tab. l Reaction of α-oxo ketene dithioacetals 2 with diethyl malonate under various conditions

The reaction products and yields of α-enoyl dithioketal and diethyl malonate are shown in Table2.

Tab. 2 Reaction of α-alkenoyl ketene- ( S，S ) -acetals 3 with diethyl malonate under various conditions

From the results in Table 2, it tends to be seen that the nature of the reaction between α-enoyl dithioketal compounds and diethyl malonate changes with the difference in the alkylthio group. When the alkylthio group is propylthio and pentyl When the thio group is available, the last response item goes through ring opening, which is equivalent to the ethylthio group and is a formed triene; and when

When the alkylthio group is a butylthio group, a multi-subbed cyclohexenone compound is at long last gotten without ring opening.

The cas no 105-53-3 is ,since the eventual outcome of the response between dibutylthio ketal and diethyl malonate is a middle of the road result of the response of other substituents, taking into account the potential reasons that influence the proceeded with response of the transitional item, attempt to change how much K2CO3 or increment the response temperature, The end result got is still cyclohexenone . 5a. The outcomes are displayed in Table 3:

Tab. 3 The reaction of compound 3b with diethyl malonate under various alkali and temperature conditions

As can be seen from Table 3, the amount of alkali has a certain influence on the reaction yield. When the molar ratio of K2CO3 and reactant 3b is 1:1, the yield is the highest, and when the amount of K2CO3 is increased, the reaction yield decreases (No. 1-3 ); when the reaction temperature is increased, the reaction yield also decreases (numbers 4-5), the reaction yield Not high is due to the simultaneous occurrence of side reactions of Michael addition reaction at the two reaction sites of reactant 3b (Fig. 2).

Figure 2 The side reaction of compound 3 with diethyl malonate

The formation of this by-product is controlled by reducing the addition rate of diethyl malonate and its initial concentration, but the effect is not very obvious. The product 4 added by Michael cannot be obtained by changing to other bases for heating. After the ethylthio, propylthio and pentylthio groups in hexenone 5 were replaced by butylthio groups, the product could not undergo reverse Michael addition reaction, and cyclohexenone became stable. The reason may be due to The size of the n-butyl group is just enough to maintain the stability of the spatial structure of cyclohexenone. 

The possible mechanism of this reaction is shown in Figure 3:

Figure 3 Proposed mechanism for compound 3 react with diethyl malonate

3 Conclusions:

The result of the reaction between α-alkenoyl dithioketal and diethyl malonate is firmly connected with the alkylthio group in its design. When the alkylthio group is a butylthio group, an intramolecular Michael expansion response happens to get a polysubstituted The cyclohexenone compound of ; when supplanted with other alkylthio gatherings, the item can’t remain on the cyclohexenone compound, and a reverse Michael expansion response will happen, and the cyclohexatriene compound will be gotten in the wake of ring opening. It is of extraordinary importance to grow the use of α-carbonyldithioketal compounds.