April 20, 1954
PREPARATION AND PROPERTIES OF
1,3-DICHLOKOBUTYL ETHERS
2255
[CONTRIBUTION FROM THE CARVERFOUNDATION, TUSKEGEE IYSTITUTE ]
The Preparation and Properties of Certain 1,3-Dichlorobutyl Ethers BY CLARENCE T. MASON,CLARENCE W. R. WADE'AND HILLARDW. POUNCY, JR.' RECEIVED DECEMBER 12, 1953 Gaseous hydrogen chloride reacts with p-hydroxybutyraldehyde (aldol) and an alcohol to give the corresponding l-alkoxy1,3-dichlorobutane in yields varying from 33 to 62%. A similar reaction occurs when or-methyl-P-hydroxybutyraldehyde1s used, but with slightly lower yields. The chlorine atom in the 1-position is replaced by reaction with sodium alkoxide, sodium acetate, Grignard reagent, malonic ester and cuprous cyanide to give new series of compounds.
Literature references to the preparation and and turn dark on standing. As indicated by properties of the monohalo- and 1,2-dihaloalkyl-l- Duliere and Pineau (refs. 2 , 3), the y-chlorine alkoxides are fairly abundant, and their appli- atom is relatively stable, while the a can react with cation to organic synthesis is well established. sodium acetate, Grignard reagent, sodiomalonic With the exception of the work of DuliereZ and ester, metal cyanides and sodium alkoxides. PineauI3however, little attention has been paid to Experimenta1 the 1,3-dichloroalkyl-1-alkoxides. Duliere adapted 3-Hydroxybutanal.-Technical aldol (Matheson) was the Henry synthesis4 to the preparation of 1,3- purified by washing an ethereal solution with a saturated dichloropropyl-1-alkoxidesby saturating an acro- solution of sodium bicarbonate and with water, the nonlein-alcohol mixture with dry hydrogen chloride, aqueous layer dried over anhydrous calcium chloride and distilled, the fraction b.p. 80-81" (20 mm.) being used imand he prepared the acetals of the resulting halo- mediately. The technical aldol can be used in the preparagenated ethers. In a subsequent paper5 he de- tion of the chlorinated ether, but the yields are lower and scribed the treatment of aliphatic and aromatic the product more difficult to purify. Grignard reagents with 1,3-dichloropropyl-l-alkox- Z-Methy1-3-hydroxybutanal.-The method of Kyriakides6 good yields when freshly distilled propanal and ethanal ides and showed that, as in the. case of the 1,2- gave were used. The portion b.p. 91-93' (20 mm.) was used dihaloalkyl-1-alkoxides,the a-halogen is the more immediately. reactive, and thus prepared a number of 1-alkyl 1,3-Dichloro-l-alkoxybutanes.-Gaseous hydrogen chloand -aryl derivatives of 3-chloropropyl-1-alkoxides. ride was passed into a mixture of 0.5 mole of aldol and 0.5 of alcohol a t 2' until the hydrogen chloride ceased to Pineau3 extended the knowledge of the properties mole be absorbed. The non-aqueous layer was dried over calof these 1,3-dihalopropyl ethers by treating them cium chloride, a stream of dry air bubbled through t o rewith a number of various reagents. move excess hydrogen chloride and the liquid vacuum disI n view of (1) the possible importance of the 1,3- tilled. Several distillations were necessary for purification, difficulty of purification increasing with the complexity dichloro-1-alkoxyalkanesas organic intermediates, the of the alcohol. When possible, the ethers were used immeand (2) the fact that aldol compounds (from which diately after distillation, as they became dark on standing are prepared the raw materials in the Duliere and even for short periods. The properties of the halogenated Pineau methods) are easily accessible, it seems ethers are given in Table I. important to investigate these aldols in reactions TABLE I similar to the Henry synthesis, and in addition, to 1,3-DICHLOROBUTYL ALKOXIDES-CH~CHC~CH~CHC~OR investigate further the reactions of the 1,3-dichloroB.p. Yield, C1 Analysis, %" 1-alkoxyalkanes thus prepared. R "C. hlm. % ~ z Z ~ D d2o4 Calcd. Found In a cold mixture of aldol, excess hydrochloric CHB 41-42 9 59 1.4399 1.1126 45.17 45.20 acid and an alcohol, the carbonyl should react in CiHj 49-50 6 60 1.4409 1.0832 41.44 41.24 the usual way to form an a-chlorinated ether, and CaH, 66-67 7 62 1.4400 1.0447 38.31 38.40 also a chlorine atom should be substituted for the C4Hs 85-86 7 46 1:4318 1.0253 35.62 35.76 hydroxyl group, to give the dichloroalkoxy product. i-CsH7 61-62 6 33 1.4380 1.0432 38.31 38.45 This has been verified experimentally, and the All halogen analyses were made by macro Parr bomb. presence of the dichloroalkoxy compound has been 1,3-Dichloro-Z-methyl-I-alkoxybutanes.-The method demonstrated by analysis. The well-known reacwas used in the preparation of these compounds. tion of the product with sodium alkoxide to give above They required repeated distillations for purification, and the acetal proved definitely that one of the halogen were relatively more unstable than the ethers without atoms was in the a-position. branching. Properties are given in Table 11. The position of the other chlorine was demonTABLE I1 strated by nitric acid oxidation of the dimethyl 1,3-DICHLORO-2-METHYLBUTYL-1-ALKOXIDESacetal to a product identified as 3-chlorobutanoic CHaCHClCH( CH3)CHClOR acid. The reactions of 3-hydroxybutanal (aldol) B.p. Yield, C1, Analyses. C.;" and of 3-hydroxy-2-methylbutanal proceed norK d", Calcd. Yo Found Mm. mally with acceptable yields. The resulting 1,3- CH3 67-68 10 55 1.4468 1.0807 41.44 41.40 dichlorobutyl ethers are water-clear liquids which C2Hs 77-78 11 54 1.4478 1.0648 38.31 38.23 possess lachrymatory properties, fume in moist air CaH7 83-84 11 43 1.4460 0.9910 35.62 35.56 (I
O C .
(1) In partial fulfillment of t h e requirements for the M.S. degree, Tuskegee Institute. (2) Ti'. Duliere, Bull. SOL. chiin., 33, 1647 (1923). ( 3 ) R. J. Pineau, J. ~ e c i z e r c h e scentre nntl. y e c h e r r h c x i . , 292 (1951) [ C . A . , 46, 416i (1952)l. (4) I.. Henry, Bull. ocad. my. Brlg., [31 26, 439 (1893). ( 5 ) W.nirlierr. BirII. SOL. ciiim.. 36, CS4 (19%).
1 ~ 2 6 ~
11 33 1.4400 1.0080 33.27 33.33 CiHs 95-96 All halogen analyses were made by macro Parr bomb. Acetals from the Ethers.-Molar quantities of the Q halogenated ether dropped slowly into cold equimolar ntnounts
2256
C. T. MASON,C. W. R. WADEAND 13. W. POUNCY, JK.
Vol. 76
refluxed and stirred until reaction ceased. To this was gradually added 40 g. (0.255 mole) of 1,3-dichloro-l-methoxybutane, the mixture allowed to stand for 12 hours, refluxed one hour and allowed to stand an additional four TABLEI11 hours, filtered, and the solids washed several times with dry ether. The filtrate and washings were combined, dried over 3-CHLOROBUTYL-1,1- D X A L K O X I D E S - C I I ~ C H C ~ C H Z C H ( ~ ~ ) Zmagnesium sulfate, and distilled to give 30 g. (43%) o,f B p. Yield, CI, Analysei. % 1,l-dicarbethoxy-2-methoxy-4-chloropentane; b.p. 143-145 R 'C. ~ z Z ~ D d204 Calcd. Found % hIm. ( 5 mm.), d2Cd 1.1053, %'OD 1.4471. 7 63 1.4160 1.0024 23.23 23.31 CH3 40-41 Anal. Calcd. for C12HnClOj: CI, 12.63. Found: CI, 11 61 1.4195 0.9709 1 9 . 6 3 19.78 12.5.5. CzHs 68-69 6 61 1.4250 ,9335 1 6 . 9 8 17.18 Similarly prepared from 14 g. (0.08 mole) of 1,3-dichloroC R H ~ 87-88 C4Hg 124-125 13 62 1.4262 ,9035 14.97 15.18 2-methvl-l-methox\butane was 8 E. f3341,) of 1-1-dicarbethox~~-2-methox~-3-methyl-4-chlo~openta~e; b.p. 138" ( 3 mm.), dZo41.0778, @ D 1.1462. 3-CHLORO-2-?rIETHYLBUTYL-I, l-DL4LKOXIDESAnal. Calcd. for C13H23C106: C1, 12.03. Found: C1, CH,CHCICH( CHa)CH( OR)* 12.45. 67-68 10 60 1 . 4 2 i j 0.9979 21.28 21.21 CHI Reaction with Sodium Cyanide.-A modification of the 10 60 1.4365 ,9658 18.21 18.16 procedure of Hemes was used. T o 53.9 g. (1.1 moles) of CzHs 79-80 ,9564 15.92 15.80 oven-dried sodium cyanide was slowly added 147 g. (1.0 C3Hi 100-101 11 61 1.4367 ,9279 14.14 14.32 mole) of 1,3-dichloro-l-methoxybutanein 100 mI. of soCdHs 133-134 13 59 1.4377 dium-dried benzene, the mixture stirred and heated a t 5867' for 30 hours, filtered and dried over magnesium sulfate. Identification of 3-Chloro-l , 1-dimeth0xybutane.-Onehalf mole of the acetal was dropped, over p o hours, into 220 On fractionation there was obtained 105 g. (72%) of 3g. of concentrated nitric acid a t 2 5 3 0 . After standing chloro-1-cyano-1-methoxybutane,b.p. 53' (10 mm.), dZ04 1.0386, %"D 1.4298. This compound was identified by conovernight the reaction mixture was distilled. The fraction version to the methyl ester (of the corresponding acid) of b.p. 108-109' (16 mm.) was identified as 8-chlorobutyric which was analyzed for chlorine. acid by its anilide and toluidide melting 89-90' and 114Sodium cyanide was found t o be superior to cuprous cy115', respectively (lit. valuesi 90" and 114'). anide. Once prepared, the nitrile was extremely stable t o Reaction with Sodium Acetate.-The method of Hen& was used. A mixture of 35 g. (0.42 mole) of fused sodium hydrolysis. The methods of Henzes using barium hydroxide, acetate, 150 ml. of sodium-dried benzene and 70 g. (0.38 Krieble and NoIP with hydrochloric acid, and Berger and Olivier,'o using 100% phosphoric acid, and that of Rietz,ll mole) of 1,3-dichloro-1-propoxybutane was heated a t 4060' with vigorous stirring for 15 minutes. After being were all tried, but were unsuccessful in producing identifistirred 10-14 hours a t room temperature the mixture was able quantities of the acid. I n each case the nitrile was defiltered, dried over calcium chloride for one hour and frac- composed and could not be recovered. Hydrolysis of the Cyano Derivative to the Methyl Ester.tionated a t reduced pressure to give 46 g. (58%) of l-acetoxy3-chloro-1-propoxybutane;b.p. 88-90" (3 mm.), dZ540.9850, Twenty-five grams (0.17 mole) of the cyano compound above, 18 g. of methyl alcohol and two drops of water were nZ6D1.4302. Anal. Calcd. for CsH17C10~: C1, 16.99. Found: C1, saturated with hydrogen chloride and refluxed. After one hour the mixture was washed with water, extracted with 17.01. ether, dried over magnesium sulfate, and fractionated. Similarly prepared was 1-acetoxy-3-chloro-1-butoxybu- There was obtained 12 g. (40%) of l-carbomethoxy-3tane (yield 78%); b.p. 104-105" (6 mm.), d26, 1.0083, n 2 b chloro-1-methoxybutane; b.p. 45' (5 rnm.), dzo4 1.0766, 1.4394. %*OD 1.42.50. Aiiel. Calcd. for CloHleCIOa: C1, 15.92. Found: C1, A n d . Calcd. for C ~ H I ~ C ~C1, O ~19.63. : Found: C1, 15.85. 19.90. Reaction with Butylmagnesium Chloride .-To approxiThe ester could not be hydrolyzed t o the acid. mately 0 . 3 mole of butylmagnesiurn chloride in ether was Reaction of the Cyano Derivative with Butylmagnesium added gradually with cooling 31.4 g. (0.2 mole) of 1,3-di- Chloride.-To approximately one-half mole of butylmagnechloro-1-methoxybutane in an equal volume of sodium-dried sium chloride was slowly added 36.7 g. (0.25 mole) of 3ether. At the end of the addition period the mixture was chloro-1-cyano-1-methoxybutane, the mixture stirred a t refluxed one hour, cooled and hydrolyzed with 1:4 sulfuric room temperature for 24 hours, the product h'ydrolyzed with acid and ice. The organic layer was separated, washed 1 : 4 sulfuric acid, extracted with ether, washed with satuwith water, neutralized with a saturated sodium bicarbonate rated sodium bicarbonate solution, washed with water, dried solution, washed with water, dried overnight with magneover magnesium sulfate and fractionated. There was obsium sulfate, and fractionated t o give 24 g. (67%) of 2-chlorotained 32 g. (68%) of 2-chloro-4-methoxy-5-nonanone; 4-methoxyoctane; b.p. 69-71' (6 mm.), d 2 0 d 0.9158, n2% b.p. 75-77' (8 mm.), d204 0.9669, %'OD 1.4311. 1.4300. .4nal. Calcd. for CloHleCIOz: C1, 17.17. Found: C1, A n d . Calcd. for CgH19ClO: C1, 19.81. Found: C1, 17.49. 19.50. This product did not form an oxime, semicarbazone, or Also prepared from 30 g. (0.18 molc) of 1,3-dichloro-l- 2,4-dinitrophenylhydrazone. cthoxybutane and butylmagnesiurn chloride was 20 g . (5970) 2-chloro-4-ethoxyoctane,b.p. 58-60" ( 4 mm.) d2'r Acknowledgment.-This work was performed 0.9041, nZ4D1.4294. with the aid of U. S. Navy funds, and under con.4nal. Calcd. for CloHzlCIO: C1, 18.40. Found: CI, tract with the Office of Naval Research. The 17.97. authors appreciate this assistance. Reaction with Malonic Ester.-Forty grams (0.25 mole) TUSKEGEE INSTITUTE, ALABAMA of malonic ester was added t o 6 g. (0.255 gram-atom) of finely divided sodium in sodium-dried ether and the mixture of the appropriate sodium alkoxide, the products filtered, dried over calcium chloride and vacuum distilled give the acetals in Table 111.
(7) E. H . Huntress, "Organic Chlorine Compounds," John Wiley and Sons, Inc., iXew York, N. V.,1948, p. 20. (R) H. R . Henze and J , T. hlurchison, THISJ O U R N A L , 6 5 , 4295 (1933).
(9) Vernon K . Krieble and Clarence I. Noll, ibid., 61, 560 (1939). (10) G. Berger and S. C. J. Olivier, Rec. tvau. chim.,46, 600 (1927) IC. A . , 2 2 , 239 (1928)). (11) Edward Rietz, Org. Syntheses, !24, 96 (1944).
