A method of obtaining a 1-chloroadamantane, 1 - and 4-chordeumatida
(57) Abstract:The invention relates to the field of organic chemistry, in particular to a method for monochloramine derivatives of adamantane and diamantane, which are used in the production of thermo - and hemostatic polymers that serve as the raw material for the synthesis of medicines and are used in the synthesis of other derivatives adamantanone (amines, alcohols, acids). The method is carried out by catalytic chlorination of adamantane and diamantane carbon tetrachloride. As the catalyst used such salts of manganese, as MnSO4, MP(C17H35CO2)2(stearate), Mn(OAc)2, MP(ASAS)3, MnCl2activated nitrile ligands (CH3SP, CH3CH2JV, PhCN, CH2(CN2)2). The molar ratio of [MP] : [RCN] :[adamantane or diamantane]:[CCl4]=1:2-4:1000:1000-5000. The process is conducted at a temperature of 200oC for 0.5 to 8 hours Technical result is an increase in the conversion adamantanone to 100%. table 1. The present invention relates to the field of organic chemistry, in particular, to a method for monochloramine derivatives of adamantane and diamantane (1-chloroadamantane, 1i 4-Hardeman.Monochloropropane of adamantanone find wide application in the production of thermo - and hemostatic polymers that serve as the raw material for the synthesis of medicines and are used in the synthesis of other derivatives adamantanone (amines, alcohols, acids, etc.) (E. I. Bagriy. Adamantanes. M.: Nauka, 1989. S. 264 ; R. C. Fort, Adamantane: The Chemistry of Diamond Molecules. N. J. Dekker, 1976, 385 p. ).The most known method of producing 1-chloroadamantane (3) is the chlorination of adamantane with free CL2by initiating the reaction by UV-irradiation. The maximum selectivity of the reaction of 1-chloroadamantane (3) is achieved by photochemical chlorination in the environment CCL4or CS2at room temperature and duration of reaction 3 hours (C. A. Nekrasov, N. And. Shuykin. WPI. THE USSR ACADEMY OF SCIENCES. Ser. chem. 3, 714 (1969) ).< / BR>Photochemical method of obtaining 1-chloroadamantane of chlorine and adamantane has a number of disadvantages.1. Method is-low-tech and environmentally hazardous due to toxicity, volatility and high activity of chlorine.2. Chlorine is a highly aggressive product and most steels in contact with him corrode, which is enhanced in the presence of moisture, the poet is E. chlorine and high pressure.3. Photochemical reaction is carried out in a transparent glass or quartz reactors, therefore, the method is characterized by low productivity and difficult to scale.One of the well-known literature methods for the synthesis of 1 - and 4-chordeumatida (4, 5) (in the form of a mixture of isomers in the ratio 1:1) is the interaction of polycyclic hydrocarbon tetrahydrobenzo-S (6) (has the same hydrocarbon composition that diamante) with acetyl chloride in dichloromethane solution in the presence of equimolar number ll3at 0oWith over 12-22 h (D. Faulkner, R. A. Glendinning, D. E. Johnston, M. A. McKervey. Tetrahedron Letters, 20, 1671 (1971) ). Total output (4, 5) in this case amounted to 80% .< / BR>This method, despite the high yield of the target products, has some significant drawbacks.1. High consumption of catalyst ll3leads to the formation of a significant amount trudnoozhidaemyh waste (ll36N2O, Al(Oh)3, HCl).2. The necessity of using intensive mixing, cooling creates problems with the implementation of technological regime.3. Use as glorieuses agent remote acetyl chloride I have Cl2(G. Lieb, C. Senger "Synthesis of organic products from small quantities of substances". Goskomizdat, 1957, L., S. 53 ). l3, PCl5and SOCl2are gloriously agents, therefore, the use of l for carrying out the chlorination refers to the appearance of extra stage.4. A significant duration of reaction (22 h). 1-Chloroadamantane (3) can be selectively obtained by chlorination of adamantane (1) using chlorosulfonic acid (B. M. Lerman, Z. Y. Aref'eva, A. R. Kuziev, G. A. Tolstikov. WPI. An SSSR, Ser. chem. 4, 884 (1971) ). The reaction is carried out at low temperatures (-5o(C) with a large excess glorieuses agent: the molar ratio of [AdH]: [ClSO2OH] = 1: 8-10.< / BR>This method has the following disadvantages.1. The necessity of using low temperatures (-5oC).2. High consumption glorieuses agent.3. High corrosivity chlorosulfonic acid and its hydrolysis products (Hcl,H2SO4).4. Great difficulties in the allocation of the target product from the use of excess ClSO2OH, you want to neutralize and decompose at low temperature (water, NaHCO3, Na2CO3).< / BR>This method unsuitable for preparative purposes, since it requires a large consumption glorieuses agent (molar ratio [diamante]:[lSO2HE]=1:58) and low temperatures. Due to the use of a large excess of chlorosulfonic acid are great difficulties in the selection of target products (4, 5), the reaction mass is poured on ice, chlorosulfonic acid hydrolyzed with the formation of Hcl and H2SO4(aqueous solution - waste), products (4) and (5) is extracted with ether from vysokokontsyentrirovannogo aqueous solution of sulfuric and hydrochloric acids. This operation is dangerous and should in glass equipment or reactors made of special steel grades.A known method of obtaining an individual 1 - and 4-chordeumatida (4, 5) by chlorination of 1-diamantane (7) and 4-diamantane (8), respectively, using chloride taanila (Ola G., P. Schilling, R. Renner, J. Kerekes, J. Org.Chem. 1974, 39, 3472-3476 ).< / BR>However, this method is difficult to use for the synthesis of significant amounts of products (4) and (5) because the original alcohols (7,8) were obtained from the chloride (4, 5) and separated using high performance liquid chromatography .Convenient method of obtaining chlorine is alreet two functions, at the same time as chairwomen the agent and the environment (H. Stetter, M. Krause, W.-D. Last, Angew.Chem., 80, N 22, 970-971 (1968) . The reaction is catalytic and is carried out in the presence of Lewis acids, preferably ll3. However, chlorination adamantane flows selectivity with the formation of a mixture of 1-chloro-(3) and 1,3-dichloromethane (9) with a predominance of the latter. The process takes place under mild conditions (20oS, 4 h), but with a large excess of catalyst ll3< / BR>< / BR>the molar ratio of [Ad]:[ll3]=1:1).When replacing ll3on another catalyst Fl3/K10(ferric chloride, applied to the cation exchanger) the selectivity of the reaction (3) is reduced to 2% (P. Kovacic, J. - H. Chen. Chang. J. Org. Chem., 36, 3188 (1971) .This method has significant drawbacks.1. Low output 1-chloroadamantane (2-13%).2. High consumption of catalyst (ll3used in equimolar the number in relation to the adamantane).3. Due to the large consumption ll3much more complicated isolation and purification of 1-chloroadamantane. After the process in the reactor is added to water (or a solution of Hcl), which reacts vigorously with anhydrous ll3(formation of crystalline lCl36H2About sproat corrosion of reactors.4. Produce large quantities of inorganic waste (AlCl36N2O, Al(Oh)3, HCl) and wastewater, which must be neutralized.A more convenient method of chlorination of adamantinoma is chlorination using chloroform under the action of catalysts: salts and complexes of salts, such as FeBr2, Fe(ASAS)3, NiBr2, Ni(acac)2, rl3Group(ASAS)3, l2Aug2With(ASAS)2With(ASAS)3pre-activated at 200oC for 3 hours in an environment l3in a sealed autoclave.< / BR>The chlorination is carried out at 200oC for 6 h with a molar ratio [AdH] :[cat]:[CHCl3]=1:0,01:3-17 and output 1-chloroadamantane (3) is 77%, 1 and 4-chordeumatida (4, 5) - 75% (and.with. 96123148/04 from 27.08.98, U. M. Dzhemilev, R. I. Khusnutdinov, N. A. Sidneva, A. I. Malikov. The method of obtaining monochloramine derivatives of adamantane and diamantane ).< / BR>The process is different selectivity for monochloromethane, substituted at the nodal positions.The method has the following disadvantages.1. A moderate yield of 77%
2. A significant duration of process is 9 h (3 h for activation of the catalyst, 6 h the process of gloriaromanasuciu (RF Patent 2125551, U. M. Dzhemilev, R. I. Khusnutdinov, N. A. Sidneva, C. N. Latypov. The method of obtaining a mixture of 1-chloro-1,3-dichloromethane.  ) is formed of a mixture of 1-chloroadamantane (31%) and 1,3-dichloromethane (69%) at 150oC for 3-5 h< / BR>The main disadvantage of this method is neselektivno process, as output 1-chloroadamantane (3) does not exceed 31%.1-Chloroadamantane (3) was obtained by chlorination of adamantane using CCL4under the action of Rh-containing catalyst: Rh(PPh3)3Cl, [Rh(CO)2Cl2]2,
Rh4(CO)12when the molar ratio [AdH]:[Rh]:[CCl4]=1:0,01:3 (RF Patent 2126784, U. M. Dzhemilev, R. I. Khusnutdinov, N. A. Sidneva, C. N. Latypov. A method of obtaining a 1-chloroadamantane ).< / BR>Registergui catalyst chlorination adamantane has the following disadvantages.1. Low activity.2. Low performance (optimal molar ratio [Rh]:[AdH] is 1:100) catalyst. This shortcoming is significant due to the high cost of rhodium salts: catalog company "Aldrich" (1996-1997,) the cost of 1 g of rhodium complexes reaches PH(h3)3CL and [Rh(CO)2Cl]2215 USD/1 g (page 1374), Rh(acac)3- 124,2 dollar/1 g ( have these disadvantages.The method consists of chlorination adamantane and diamantane use of carbon tetrachloride under the action of salts and complexes of manganese, such as MnSO4, Mn(C17H35CO2)2(stearate), MP(ASAS)2, MP(SLA)2, nl2activated nitrile ligands (CH3CN, CH3CH2JV, PhCN and other) at 200oC for 1 h, at a molar ratio [Mn]:[RCN]:[AdH] or [diamante]:[CCL4]=1:2-4:1000:1000-5000, preferably 1:2:1000:3000.Under optimal conditions (200oS, 1 h, when the molar ratio [Mn]:[RCN]: [AdH] :[CCl4]=(1:2:1000:3000) the output of monochloromethane (3, 4, and 5) reaches 89-98% at complete conversion of the original adamantanone (1, 2).The process has a high selectivity for monochloromethane, substituted at the nodal positions (no impurities dichlorsilane and replaced in the bridge positions of carbon atoms adamantanone structures).< / BR>< / BR>Significant differences of the proposed method from the prototype.1. B as a complex catalysts chlorination adamantane and diamantane using carbon tetrachloride are used manganese compounds, activated nitrile ligands.3. If in the known method of chlorination rhodium catalyst is used in the ratio of [Rh]:[AdH]=l:100, offered only to 0.001 moles of catalyst relative to adamantane (or diamantane).The advantages of the proposed method are as follows.1. High yield of the target product and a high selectivity to monochloramine adamantane derivative and diamantane (98%).2. Low consumption of catalyst.3. Simplification of procedures for isolating the desired products due to the use of small amounts of the catalyst and the absence of side-reaction products.4. Reducing waste due to low consumption of catalyst.5. The availability and low cost of the used catalysts.6. Unreacted CCl4without additional purification may be returned in the response.7. Reduce the cost, reduce labor and energy costs, environmental safety.The proposed method is illustrated by examples:
EXAMPLE 1. Reactions were carried out in glass vials (V=20 ml) or steel mikroavtobus (V=17 ml) (the results of parallel experiments do not differ).In the glass the l of carbon tetrachloride. The ampoule was sealed and heated in an oil bath for 1 hour at 200oC.After the reaction, the ampoule was cooled to room temperature, opened, the reaction mass was filtered through a layer of Al2ABOUT3(2 Gy).Unreacted CCl4drove away, the residue was distilled in a vacuum with air refrigerator (78-82oC/1 mm) - this is the sublimation of 1-chloroadamantane (3). Selected (3), and recrystallized from methanol. had topl. 164-165oC (lit. data 163-164oWith) [3, 4, 6].Obtained 0.33 g of 1-chloroadamantane, yield 98%.EXAMPLE 2. In a glass ampoule with a capacity of 20 ml (or steel mikroavtobus V=17 ml) were placed 0.002 mmole of catalyst MP(SLA)2, of 0.004 mmole acetonitrile, 0,38 g (2 mmole) of diamantane, 1-3 ml of carbon tetrachloride. The ampoule was sealed (mikroavtobus hermetically closed) and was heated on an oil bath at 200oWith 1 hour. After the reaction, the ampoule was cooled to room temperature, opened, the reaction mass was filtered through Al2ABOUT3(2 g), unreacted CCL4drove away, the residue was led from acetone to remove unreacted Diamantina. The output of chloroadamantane was 95%. Division ASS="ptx2">1-Hardemann (4): so pl. = 250-252,5oWITH
IR spectrum (Vmaxcm-1): 1067, 972, 880, 808, 720
Range PMR1H (,, m d,, CDCl3TMS): 2,43 (2N, WITH3WITH14), and 2.14 (d, 2H, WITH13), a 1.88 (m, 5H,2WITH7WITH9WITH11WITH12), 1,25-to 1.60 (m, 10 H).An NMR spectrum13With (,, ppm, CDCl3TMS): 24,86 d (4), 30,46 d (9), 33,10 t (3), 36,90 d (6), 37,25 d (8WITH10), 37,89 t (5), 40,55 d (7WITH11), 44,66 d (2WITH12), 49,16 t(C13),76,27 c (C1).M/e 224.4-Hardemann (5): so pl. = 75-76oWITH
IR spectrum (Vmaxcm-1): 1079, 1070, 1049, 1044, 982. 969, 852, 829, 797, 709, 529.Range PMR1H (,, m D., CDCl3TMS): 2,09 (d, 6N,3WITH5WITH14), 1,74 (sh.s, 3H),2WITH6WITH12), 1,27-of 1.65(m, 10H).An NMR spectrum13With (,, M. D., CDCl3TMS) 25,00 d (9). 35,12 d (C1C7C11), 36,65 t (8WITH10WITH13), 40,22 d (C2WITH6WITH12), 47,77 t (3WITH5WITH14), 65,6 (WITH4).M/e 224.This same methodology was carried out all other experiments, the results of which are shown in table 1.It is established that the optimum temperature is 20 the high - observe the formation of resinous products. If 200oThe optimal duration of the reaction is 1 hour. With increasing duration of experience observed the formation of polychlorinated adamantanone. A method of obtaining a 1-chloroadamantane, 1 - and 4-chordeumatida General formula
< / BR>< / BR>< / BR>catalytic chlorination of adamantane and diamantane using carbon tetrachloride, characterized in that as catalysts for the chlorination use salts of manganese (MnSO4, nl2, MP(C17H35CO2)2(stearate), MP(SLA)2, MP(ASAS)3), activated nitrile ligands (CH3SP, CH3CH2CN, PhCN, CH2(CN)2) at a temperature of 200oC for 0.5 to 8 hours at a molar ratio [Mn] : [RCN] : [AdH or Diamanten] : [CCL4] =  : [2-4:  : [2000-5000] .
FIELD: organic chemistry, chemical technology.
SUBSTANCE: method involves the alkylation reaction of adamantine or mixture of alkyladamantanes with the general number of carbon atoms 11-20 in methylene chloride solution medium at temperature 15-25°C in the presence of catalytic system representing an equimolar mixture of aluminum halide and halide-containing promoter of the general formula: AlX3 x CpHrXz wherein X means Cl, Br; p = 0; r = 0; z = 2, or P = 1; z = 4, either p = 1; r = 2; z = 2. The conversion of adamantine is 78-94%. Invention provides the development of the improved technological procedure for preparing the end substances with the enhanced importance.
EFFECT: improved preparing method.
7 tbl, 16 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to chemistry of adamantanes, namely to a method for synthesis of 1-aryl-4-oxoadamantanes of the general formula: wherein R means -CH3, -OH, -N(CH3)2, -OCH3. Method involves interaction of 1-bromo-4-oxoadamantane with benzene derivative chosen from the following order: toluene, phenol, dimethylaniline or anisole in the mole ratio of reagents = 1:(506), at temperature 100-180°C in the presence Lewis acids AlCl3, FeBr3, ZnCl2 for 5-8 h. Method provides synthesis of novel compounds that are semifinished substances in synthesis of biologically active compounds.
EFFECT: improved method of synthesis.
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to chemistry of adamantine derivatives, namely to a method for synthesis of 1-dialkylamino-4-oxoadamantanes of the general formula: wherein R means Method involves substitution of bromine atom in 1-bromo-4-oxoadamantane for dialkylamino-group in interaction with dialkylamine chosen from the following order: piperidine, morpholine or piperazine in the mole ratio of reagents = 1:((3-4), at temperature 190-220°C for 7-8 h. Invention provides synthesis of semifinished products used in synthesis of biologically active substances.
EFFECT: improved method of synthesis.
FIELD: organic synthesis.
SUBSTANCE: invention relates to improved method of preparing title compounds depicted by general formula: , wherein R1 = R2 = H : R = N(CH3)2, OCH3, C(CH3)3; R1 = H, R2 = CH3 : R = N(CH3)2, C(CH3)3; R1 = R2 = CH3 : R = N(CH3)2, which are intermediates in synthesis of biologically active products, via reaction of 1,3-dehydroadamantane or homologues thereof with benzene derivatives selected from series: N,N-dimethylaniline, anisole, and tert-butylbenzene at molar ratio of reactants1:(5-6), respectively, in a benzene derivative at 120-130°C for 5-6 h.
EFFECT: expanded synthetic possibilities.