72492-12-7

• 常用中文名：螺佐呋酮
• 常用英文名：SPIZOFURONE
• CAS号：72492-12-7
• 分子式：C₁₂H₁₀O₃
• 分子量：202.20600
• 发布时间：2018-07-11 04:43:37
• 更新时间：2024-01-08 09:34:18

• 用于胃溃疡。

名称

• 中文名: 螺佐呋酮
• 英文名: spizofurone
• 中文别名: 5-乙酰螺[苯并呋喃-2(3H),1'-环丙烷]-3-酮; 螺喃酮
• 英文别名: Maon; AG-629; 5-acetylspiro[benzo[b]furan-2(3H),1'-cyclopropane]-3-one; Espizofurona [spanish]; Spizofuronum; 5-acetylspiro<benzofuran-2(3H),1'-cyclopropan>-3-one; Espizofurona; 1'-cyclopropane]-3-one; 5-acetylspiro[benzo[b]furan-2(3H)

物化性质

• 密度: 1.33 g/cm3
• 沸点: 396.3ºC at 760 mmHg
• 熔点: 150-155ºC
• 分子式: C₁₂H₁₀O₃
• 分子量: 202.20600
• 闪点: 180.6ºC
• 精确质量: 202.06300
• PSA: 43.37000
• LogP: 1.99690
• 折射率: 1.61
• 分子结构:

  1、 摩尔折射率：52.41

  2、 摩尔体积（cm³/mol）：151.0

  3、 等张比容（90.2K）：408.4

  4、 表面张力（dyne/cm）：53.3

  5、 极化率（10-24cm3）：20.77

• 更多:

  从乙醇结晶，熔点102～104℃；106～107℃。

毒性和生态

毒理学数据: 急性毒性LD50雄、雌小鼠，雄、雌大鼠(mg/kg)：1810，1740，5630，5640口服。 CHEMICAL IDENTIFICATION RTECS NUMBER : WG9807500 CHEMICAL NAME : Spiro(benzofuran-2(3H),1'-cyclopropan)-3-one, 5-acetyl- CAS REGISTRY NUMBER : 72492-12-7 LAST UPDATED : 199612 DATA ITEMS CITED : 9 MOLECULAR FORMULA : C12-H10-O3 MOLECULAR WEIGHT : 202.22 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5440 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,541,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 609 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,541,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1610 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,541,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1740 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,541,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 840 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Nutritional and Gross Metabolic - body temperature decrease REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,541,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1770 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,541,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 35 gm/kg/5W-C TOXIC EFFECTS : Gastrointestinal - other changes Liver - other changes REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,547,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18200 mg/kg/26W-C TOXIC EFFECTS : Liver - other changes Related to Chronic Data - death REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,577,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 10500 mg/kg/5W-C TOXIC EFFECTS : Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,559,1986

合成路线

72491-93-1 ~90% 72492-12-7

文献：Kawada; Watanabe; Okamoto; Sugihara; Hirata; Maki; Imada; Sanno Chemical and Pharmaceutical Bulletin, 1984 , vol. 32, # 9 p. 3532 - 3550

80901-29-7 ~69% 72492-12-7 94243-45-5

文献：Chemical and Pharmaceutical Bulletin, , vol. 32, # 9 p. 3373 - 3377

16475-90-4 ~% 72492-12-7

文献：Chemical and Pharmaceutical Bulletin, , vol. 32, # 9 p. 3532 - 3550

72492-92-3 ~% 72492-12-7

文献：Chemical and Pharmaceutical Bulletin, , vol. 32, # 9 p. 3532 - 3550

80901-29-7 ~% 72492-12-7

文献：Chemical and Pharmaceutical Bulletin, , vol. 32, # 9 p. 3532 - 3550

80901-29-7 ~% 72492-12-7 94243-46-6

文献：Chemical and Pharmaceutical Bulletin, , vol. 32, # 9 p. 3373 - 3377

5061-21-2 16475-90-4 ~% 72492-12-7 94243-46-6

文献：Chemical and Pharmaceutical Bulletin, , vol. 32, # 9 p. 3373 - 3377

上下游产品

上游产品  5
72491-93-1 80901-29-7 16475-90-4 72492-92-3
5061-21-2
下游产品  1
95449-94-8

制备

方法l：在室温和搅拌下，将5-乙酰基-2-羟基苯甲酸甲酯(8.0mol)加到1.32kg碳酸钾在2.0L二甲基甲酰胺的悬浮中。在60℃加热1h后，在5℃和3h内加入1.32kgα-溴-γ-丁内酯。加毕在45℃下搅拌10h。冷却，过滤除去不溶的无机物。滤液减压浓缩，剩余物真空蒸馏以移去没有反应的5-乙酰基-2-羟基苯甲酸甲酯。剩余物(粗品化合物(I)，用甲醇重结晶后，熔点112～113℃)溶于2L甲醇和2L 50%氢氧化钠水溶液。并于60℃加热。冷却后，将反应液倾入1.5L冰水，用2.2L浓盐酸酸化。过滤收集析出的沉淀，水洗，干燥。溶于1L二氧六烷和1L甲苯。加入400g对甲苯磺酸，在装有分水器的装置中加热回流8.5h。减压浓缩，剩余物倾入10L冰水。过滤收集析出的沉淀，水洗，干燥，溶于乙酸乙酯。干燥后浓缩，用丙酮-甲醇重结晶，得化合物(Ⅱ)，总收率45%，熔点155～158℃。
1.26mol化合物(Ⅱ)在2.8L乙酸酐的溶液和560ml三乙胺加热回流。减压浓缩，剩余物倾人3L冰水。过滤收集析出的沉淀，洗涤后，用甲醇重结晶，得化合物(Ⅲ)，收率55%，熔点132～134℃。
7.4mol化合物(Ⅲ)和94g氯化钠溶于1.5L二甲亚砜，在150℃下搅拌1.5h。冷却后，倾入冰水。过滤收集析出的沉淀，水洗，干燥，用乙醇重结晶，得螺佐呋酮，收率88%，熔点。102～104℃。
从化合物(I)也可直接得到化合物(Ⅲ)。化合物(I)(4.7mmol)在15ml乙酸酐的溶液和3ml三乙胺加热回流10h。减压浓缩，剩余物倾入冰水，用乙酸乙酯提取。提取液水洗，干燥，减压浓缩。剩余物用硅胶层析，四氯化碳-丙酮(5：1，体积比)洗脱。收集第二组分洗脱液，用甲醇重结晶，得化合物(Ⅲ)，收率47%。
方法2：一步合成法。以5-乙酰基-2-[(四氢-2-氧-3-呋喃基)氧]苯甲酸甲酯(化合物(I))为原料，可一步反应得到螺佐呋酮，但对试剂要求较高。
将4.17g1，5-二氮双环[5．4．0]十一烯-5(DBU)和67g氯化钠溶于1L二甲基甲酰胺，在150℃和搅拌下，于2h内滴加5-乙酰基-2-[(四氢-2-氧-3-呋喃基)氧]苯甲酸甲酯(278g，lmo1)在1.8L二甲基甲酰胺的溶液，加毕再搅拌2h。减压蒸去溶剂，剩余物用水稀释后，用二氯甲烷提取。提取液洗涤，干燥，通过硅胶进行脱色。二氯甲烷溶液减压浓缩，产生的结晶再用乙醇重结晶，得136g螺佐呋酮，收率67%，熔点106-107℃。