NOMENCLATURE “Preparations ae listed under the names which are uted eam- rmonly for Uhe compounds. For the convenience of those who swish to make a complete survey ofthe iterature on any peepara- tion, the Chemical svat indexing name foreach compound is siven asa suite when that name differs fom the ttle of the preparation NOTICE TO SUBMITTERS OF PREPARATIONS Organic Syntess invites the submission of prepsrtions of compounds which are of general interest or which ilstrate tseel synthetic methods. Preparations are weleamed partiou- larly from those wh have had evasion to work out the optimum conditions of preparation. ‘The directions should be written in the style employed inthe latest volume of Organic Sytietes. Full ‘details for all steps should be inclded, and the range of yields should be reported rather than the masimam yield obtainable ‘Two copies f the directions should be sent to the Secretary. Additions, corrections, and improvements to previously pub- lished preparations are likewise welcome ACROLEIN ACETAL AND -ETHOXYPROPIONALDEHYDE "ACETAL (eroten, diethyl acetal, and proplosaldehyde, ethoxy, diethyl acetal) cH—cucHo 2%, (CHy=CHCH (OCaHa)s + C3HLOCHLCHLCH(OC3H)s ‘Sion ty Pas heed iy Rema Dea and W. Sato Se 1, Procedure A mistore of 158 g. (5.6 moles) of acrlein (Note 1) and 450 ml of absolute alcohol (ote 1 i placed in a 11. Florence ‘ask, The neck ofthe flack is closed by’ plug of eatin, and ‘the flak is hen omsersed up tits neck in an ice bath containing bout 1.5 kg. of fc When the temperature of the mixture is ‘bout 6°, 50 ml of absolute alcohol containing 2 g of hydrogen Chloride is added with swing. "The temperature is apt to Fee very rapidly. The fas i damped firmly in place end lft 48-60 hous; the ce is llowe to melt and is not renewed. ‘The contents of the Mask are ranserred to a 1.1. round bottomed flask, 05-1 g of copper cazbonate is add, and the Tiqui i fractionally distiled dw sacu with th aid of w Fenske column (Fig, 1) (Noles 2 and 3). The following fractions are collected. iow 5/2 mn, ein an aed ote) ‘item Acouin etl te 9 sm Sealim, pisompolonliyce al Soe ‘The yield of acolein acetal is 9-108 g. (24-20%), and of ethorypropionsldchyde acetal, 08-132 g. (21-2674) (Note 1) ore St, 9,9.490,2. Notes 1. The commercial products are used. ‘The stabilizer in acroein isnot removed. 2. This design of Fenske ractinating column (Fi, 1) con- @__ sstsessentally of a packed las tube (4) $i ——_whichis provided with two heat iauat- ing jackets (8 and C) and total refx lable take-off head (D, B, and 2% “Weis constrocted of Pyree law and filed with single elx copper spins Altough the dimersions are probably aren |] fs, sot critical, tial and enor have proved . this particule design tobe eficient, rug ged, and well adaptable to numerous LAID, boratory separations, Mixtures com z pounds bling rom about O° to 400 at 1 760 mm, have ben Iractiosted se tlueneslfonate® Other procedares donot appt to boot preparative vale. $end Foy Fo Chen 1 2, aaa Ba ye a, 8.07. “Gn tl Brae CoS 5230rs ‘oncatte suTIESES {sn-BUTYLPYRROLIDINE (Pyroicine, t-butyl) es nao,, HCH, Orcutt ant - -cyttyanct 22 Neate dices Sutil by Gtone I. stout, Ose Ros and Tos F Manse, Goad Fie eta Yar hase 4. Procedure This preparation mt be carried Uough the ring ease with: out ideruption. ‘The apparatus is aranged atin Hig. 3. In a bottle of about 1.54. capacity are placed 645g. (05 mole) of diaebutylamin, 350 ml. of ligrin (Note 1), and 380 ml of 3 sodium hydroxide (Note 2). "The bottle i ited with an inlet tube which pases conly 1 in. through the stopper. ‘The mixture i cooled ina ice bath (Note 3), and ehorine fom a cylinder is pasted in under Dressure (Note). The tts kept in thee bath and ie shaken {ring the edition to aid in absorption of the gas. The rte of shaking apd the valve on the chlorine eytinder are 9 regulate thatthe pressure as Indicated on the manometer is maintained between 100 and 150 mm, (Note 8). The addition ofthe chlorine Js continued until the white fumes of the hydrochloride, which focm when chlorine comes in ntact with the amine vapor, di appear, and the non-aqueous layer takes om a greenish yellow colo, due to a aight excess of chlorine, ‘This indicates that hlovination Is complete (Note 6) ‘The ligroin solution ofthe chloramine is sparated feom the aqueous layer ina chilled, short-stemmed LL separatory funnel ‘and washed successively with 50 mi. of ice-cold 3 sodium Inydroxide (Note 7), 50 ml of ice water, and $0 mi. of cold 2 "or Spe Cal. Vl 3 290, eBUTYLPYRROLIDINE 18 sulfuric acid. The ligroin sclution becomes nestly colores ‘The chloramine i extracted from the solution with slic acd in the following manner. An ice-cold mixture of 200 ml of con- centrated sulturic acid (Sp. gr. 1.84) and 80 ml. of water is allowed to sta in contact with the igen solution fr 10 min- ‘tes withou! shaking, then fr 20 minutes with ocastonal shaking; Novonter yee Raton bt, the mixture is kept col by immersion in an ice ath, Alter cep- aration from the acid layer, the Higron is extracted with to ‘60-ml. portions of eslé concentrated sulfuric acd. ‘The combined sullurc acid extracts are used for ring doaure (Note 8). "The Tigra, which containe not mote than trace of eHloramine, is discarded, ‘ATLL wide-mouthed Eeleameyer Sas, fited with » propellr- type stirrer and a theemometer, ft in an ot bath, A mistue ‘of 40 mi. of concentrated sulfuric acd and 10 mi of water is placed in the Has, the oll bath is Heated 0 120°, and the cold6 oxcante svernses sulfure acid solution of the chloramine i allowed to fw nto the Ieated acid from the shor-stemmed sepazatory funnel (Note 9). ‘The editinn, which requzes 80-40 minutes (Note 10), bs acied ‘out at such arte thatthe temperature ofthe reaction mixture in the Basis dropped irom 120° rapidly to 95° bythe addition of the cold chloramine solution, and thereafter at sich arate that the temperature ofthe reaction mixture retnns at 0-100", preera- Dy at 95%. The reaction is exothermic, and the rise in tenpers- ture is contrlled bythe adton of the col chlramine sluton ‘To avoid an undue ese in temperature after the lactation of the chloramine, the oll bath is removed, and the flask and con tents are allowed to came to room temperate ‘A'S task sited with eparatory funnel and arcanged for steam disilation® “Two liters of crushed fee is placed in the flask, and the sulfuric aca solution, cooled to 0, islowiy add The amines are then Uberate (Note 11) by adding cold concen- trated sodium hydroxide solution (680 gin 1.3 L of water) ‘through the separatory funnel. The amines are steamed and collected in @ solution of 100 ml of concentrated hydro hori acid (pg. 119) nd 200 ml of water (Note 12). Dist Javon is continued wt al mine has passed over as incated by 4 negative test with litmus paper. About 2 1 of ditlte is sual required ‘The amine hydrochloride soltion is evaporated nely to ‘yess on a steam bath (Note 13) and transfered with about 300 mi of water to a 11. three-necked ask equipped with a Miser separatory funnel and condenser, The stirrer i started, ‘and the acid solution is cole to O° by immersing the ask in a je bath. The amines are Hberated by adding slowly 100g. of sedium hydroxide dissolved in 250m of water. Hinsterg separation. To this solution, which shoal be cold (5-89, i now added 28 g of benzeneslfonyl chloride and the mixture is sired vigorously for 30 minutes, The separatory funnel s replaced by a stopper bearing « thermometer, and the og Sn, 21,9 109 Sore Spt a Vo 3 3 (10, Ope Sts CYL 1,84 4eBUFVEEVRROLIDISE " contents ofthe flask are warmed to 40° and stirred unt the odor of the acd chloride eno Tonger noticeable. This usually requires bout a half hour. ‘The Lar-butylpyradine is separated (Note 14) from the nonvolatile cfbutylbenzeneslfonamie by steam citation, the amine being cllected in elute aid (Note 12) as before. The ac tluton is then evaporated to drynes, andthe amine ie berated by adding 20% sodium hydeose sale ton until the aqueous layer tums red tus Bue. The amine fs extracted by one 200mm. portion of ether, andthe ethereal sol tion is dred over 15-20 pellets of potassium hydroxide. After the ethers been disiled from the decanted solution, the re ues distilled from an oll bath. The yield of Ca-butylpyr- toliine boiling at 154-155°/788am. i8 4-81 g. (10-80%); nf 1437 (Note 15). 2, Notes 4 Any fraction bling within the range 60-80° may be use 2 Thisis obtained bydisoving 42 of sodium hydeoxidein 350 ml. of water : 3 All equipment, the solutions, andthe chloramine x should be kept feild to prevent decomposition during the ‘preperation, Apparatus ray be stared ina rergerator “4 As the addition of chlorine is started, the stopper inthe reaction bottle is loosened: momentarily and the chlorine is Allowed to replace snot of the air in the system '. Asthe chlorine passes niall into thobotle, the pressure rises rapidly. Shaking greatly increases the rate of absorption, fand the pressure drops, The chlorine valve i then regulated 0 45 to maintain the proper pressure with shaking, One hundred nillineters wat selected as the approximate pressure, since the rate of chlorination under this prseure is satisfactory. 6. Alage exces of chlorine ie undeseable and may rel in sreatly decreased yields. ‘The time required varies widely, ‘lependent upon the chlorine pressure maintained and the vigor ofthe shaking. ‘The checkers found that 20 minetes was ample undo thie conditions; Ube submitters reported thet 60-90 mis ‘tes was require7. If the green coor, due to excess chlorine, i not removed by one washing, the operation is repeated many tines as may he neceary, '8, The sulfuric acid layers are transferred directly into the ‘o0-ml.short-stemmed separatory funnel to be wsed in the next, step._‘The solution, which usually has aight brown enor, should be cold and well ned before the ring laure operation, ‘The ratio of ac to water is important, and only the amounts spec- Sed shoul Be wee ‘9, The funnel and contents may be supported over the reac ‘ion Bask daring the alton without cooling 10, The rate of ation should be as rapid as possible pro ied that the proper temperature ia maintained. Deviation of more than 5° from the optimum reaction temperature of 98° re ult in edd yields 11. This resction is vigorous, and the solution of alkali should be added slowly while the Sask i shaken gently with a rotary motion 12, An adapter (rabber connector and glase tube) from the lower end ofthe condenser should extend blow the surface of the absorbing acid in the receiver. To reduce fuming, a 3 to 4mm, layer of irons placed over the aid solution, "The acid olution ray be stir eccasonally. 18, Use of reduced pressure considerably diminishes the time required 1 The amine can be separated fom the sulfonamide by ex ‘eacting both with ether, drying this extract over solid potassium hydride, and fractionating. ‘The pyrrolidine dais smoothly, bt the yl ie alightly lower. 18. Several other pyrolidines of this series can be prepared by the same general method. ‘The temperature requted for Hing clonure end the percentage yield of pyrrolidine vary with the Afferent emines use. The following temperatures re given 3 ‘proximately correct for the ring dase othe N-chloro desva tives of the amines Isted. With lower boling pyrrolidine, incomplete separation from the ether may result in lower ies sehen tat wo {ateor mae Bisietet erg Rtas Sette so 12 Dimelylpyrsiine Biusteam fom {eth 2epytsine Maiginceit on Mtg: bteesiine 8, Methods of Preparation a-Btylpyrotidine can be prepared also by heating the conesponding N-bromoamine in concentrated sulfuric acid * fa by the catalytic reduction of N-batylpyrele® The pro- ‘erdure deveribed is adapted from the preparation reported in tater work ja lee detail P-CARBOMBTHOXYPROPIONYL CHLORIDE, (Propionic acid chloroform), methyl eter. CHCO, mane, CHHOOCHS gooy CHACOACHs bac? bincout ~ bxscoa Subd by Fs Can (Grok ty © Aan and €.V. Wasa 4. Procedure AL Mol Ipdrogon suecinae. A misture of 400 g. (4 moles) of sacinie anyrdide (Note 1) and 194m. (48 melee) of metha- rol (Note 2) im oand-bttomed las is refed on star ‘bath After about 36 minates the mixture ie swirled frequently ‘utili becomes homogencous (this requires 1§-30 minutes); the ‘Bas fs then half immersed inthe steam bath for an additional 50-25 minutes (Note 3). ita, US pat 1407408 C4. 8, 209 92 {ote Youyan B , 20 C28), oman nd Cate, Ch, 720108)» loncantc svwTHeses| ‘The excess methanol i removed by distillation #4 sacua (rater pap) fom a steam bath, andthe residual gud spouted {nto an 18-to 2S-cm. evaporating dish which is cote in a shallow pan of cold water. As dhe half ester eystalie, its steed and Scraped ofthe dish in order to prevent formation ofa slid cake, Alter being dried to constant weight in a vacuum desiccator (6-$ days), the product weighs S02-807 g. (08-96%) and melts at 87-58" (Notes 4 and 9) 'B. BCarbometioxypropiont corde. In a 1A, ask (Note 6) Dearing a relax condenser are placed 264g. (2 moles) of methyl hydrogen succinate and 290 ml. (4 mole) of thionyl chloride (Note 7), and the solution is warmed ina bath at 30-10" for 3 hours (Note 8). The condense is replaced by a modi Clasen still ead, the exces thionyl chloride s removed ona stcam bath fn exan, and the p-carhomethoxypropionyl chloride ie distilled (Notes 9 and 10). ‘Tho yield of eoloress provtct is 270-278 g, (0-199), bp. 9209/18 mm, (Notes 11 aid 12) 2. Notes 4. Eastman’s succinic anhydride (rm. p. 115-116") was usd 2. Synthetic methanel wae used. Since thie anhydrous alcohol is hygroscopic, partially filled bottles that have been ‘opened intermittently inthe laboratory should be rejected, 3. Thirty minutesis allowed if solution resulted after 18 min tes of swing; 25 minutes if 30 minutes was needed for homo rene. "The time factor i very important._In one ran in wich the mixture war heated fora total of $8 minutes, a product was ob tained which was shown by tation to contin about 6% of am Iydride, Longer heating than that specified incenses the yield of diester. Any change in quantity of materials wed may necesita new sof conditions in onder tabla the masa sit. ‘4 The checkers prefer the following procedure, which can bbe eared throagh in one day. A suspension of approximately ‘neha of tho crude preduct in 780 mi. of carbon disuide is ACARROMESHOXYPROFIONYT. CHLORIDE. a swarmed on a seem bath; two layers fom, in which some solid mains in swpension, This i dissolved by the addition of 4350 ml of ether, ‘The whole Is chilled to O°, and the sl si ere by suction, ‘The other half ofthe crude product is now ‘tslved in this trate, the elation i gain chilled to 0°, and the sold i filtered. The combined yield of ald ester, mp. 7-885 i 436-449, (BS-8SY%). A further 52-87, (67%) of less pure material (mp, 56-S1°) can be abtained by concentra ing the trate to Bal ts volume and ehiling to 0° '. The proct, which is suiciently pare forthe Next step, contains atleast 98% methyl hydrogen sucinate as shown by titration or dstilation throvgh an. 16in. Podhidsiak-type colar. 6, Bgulpment with ground lass joints is used throughout. 7, Bastman’s thionpehlorde (bp. 75-76") was used. The checkers obtained equivalent yields ofthe chose by using only 20% excess of thionyl chloide, "The mixture was heated for 1 bout at 40°, llowed to stand overnight, and heated again for 2 hour at 40 8, Since Iydiogen chloride is evolved, itis advisable to wor in boot or employ’ gas trap. 9. A electric eating mantle * i convenient 10, Other bling pints ae #5.5-87°/13 mm. and 89-90°/15, mom, ‘The use of as Tow a pressure as posible is advisable, since the substance tends to lose methyl chloride and form suecinic anhydride 1. The submitercbtained the same yd when phosphorus pentachloride was used insted of tony] chloride. Consistent "eaults were obtsined with the former reagent only when the acid Corie wos distilled at presures below $ mm, (bp. $8-59°/2 12, Ethyl hydrogen adipat and ethy! hydrogen sbacate may be converted (6 the corzesponding ester acid chlorides by this procidre in about the same yes. Distilation should be ca ried out rapidly at a presure of mm. ot lowe. Spt Cal Vl 8.4 99, +S Spl by te in Cl Apparat Conpany, Tee at ins2 ozcanic svwrHests 18, Methods of Preparation Methyl hydrogen succinate has been prepared by heating succinic acid with methyl succinate by treating ethyl succinate with sodium methonie? and by heating succinic anhydride with ethanol {Cerbomethoxypropionyl chore has been prepared from methyl hydrogen succinate by the use of thioay! chloride* ot phosphorus pentachloride® ‘2.CHLOROCYCLOBEXANONE (Cxcohexanone,2chloro-) we Be é e FC Noo Ha Neo Foe Tt Lait BO Hc cH : dur VW \/ e He He Suid by MS Nesey MCD, Pa a es, 4. Procedure Ine 31, three necked, round-bottomed Mask, tte witha gas inlet tube reaching almost to the bottom, a sealed mechanical stirrer (Note 1), and a gas outlet tube connected to & mercury valve (Note 2) are placed 204 g. (3 moles) of cyclohexanone (Note 3) and 900m. of water. After the reaction vessel tas been "Roun nd Sten, Bl nl, (4, SH (25 ‘omen Monty B47 Goi). ‘hans Sudboragh ta Sean J Cw, Si, 8, $9190, Cie Tsim Car 1 (AD “Rod Mase a in say 298 08, 2.CHLOROCKCLONEXANONE 2 swept out with chlorine, the gas outlet tube is eormected to the imercity valve, the Bask is cooled ia an ce bath the ster i farted and 218 g, (lightly more than 3 moles) of chlorine Dubbed in as saplly asthe gas is absorbed (about 45 minutes) ote 4). “The beaver chlorocycobexanone layer is separated and com bined wth three S0-ml ether extracts ofthe aqueous phase, and washed with 190 ml of water andl then with 200 ml of saturated todium chore solution. After Station (gravity) through finytdrous sadam sulfate the ether Is removed and the residue Yacuumedistiled in a modifed Claizen flask. ‘The fraction (00-340) boiling below 100" at 10 mm. (Note 8) is collected (Note 6). This material then fractionated carefully under r= ducal pressure by means of a 42:in, modied Vigreur cluma (heated) with a total condensation variable takeof head (Note 1). The gied of 2ehlorocydohexanane boling at 90-91°/19-15 sum, ¢ 240-265, (61-669,) (Notes 8 and 9). 2, Notee 1. A large propellertype ster fs satisfactory. ‘The Blades should be pit to drive the liga upwards, and the propeller Should be locate jast below the surface ofthe liquid to provide Splashing. ‘The checkers used a glycerotubricated rubber tube eat 2, ‘The mercury valve consists ofa tbe dipping about 0.8 in. into some mercury in & vente test tube, Thisallows the reaction tobecarted out under a sight pressure of chlorine. ‘The checkers founda water valve toe more satisfactory. The outlet tube was ‘made to dip about Ti. ino water na vented glass tube. A trap (25a suction ak) was placed between the water valve and the reaction flask to prevent water from being sucked into the reaction minture 3. "The checkers used Eastman's eydohexanone being at 181-156°, ‘The submitters ceport that the Practical grade gives just as god yields or Sto 1 409a orcante svwrmses 4. Carell contol of the temperate is unnecessary as ap proximately the same results ee obtained when the temperature Isallomed to ree to about S0° or is kept below 20°. However, at the lower tenpersture a greater amount of eydlohexanon recovered ‘5 Or below 110°/18 mm, oF 92°/8 mm, 6, Thie preliminary purlieaton ie advisable por to careful fractionation, 7. The head used was similar to that described by Turk and Matuszak? except for tho stopcock which was of the vaiety described by Newman? ‘8. This material shows a long fat st 252° cor. jn time temperature coling curve. Tt can be stored ina rehigerator i parafin-covered stoppered! bottles for long peti of time withe out dscloration, 9, About 15-10. ($-13%) of eyelohesanone, bp. S2°/14-18, sm. is recovered 8. Methods of Preparation 2-Chloroeyclohexanone can be prepared by chlornatng cyto- fhexanone in glacial acetic acid a the solvent, by passing chlorine into a mista of cyclohexanone or eycohexanol and water in the presence of powered calium carbonate, by the electrochemi- cal chlorination of eyeloexanone in hydrochloric acd” by the ‘ction of monochloroures in acetic acid om the ketone," and by ‘the oxdation of 2chloroeycohexanal" ek and Mak Ind Be Che, al, 72 (0 ry ag Ch A 0. ‘Rae od Ree A Ch Sor 08 (6 ‘tad Get J ot Chem) 18 8890), "Fl da Cle 4s 39 0) Remnant Chow, Cm rnd, 1, Mer thm, 91 (Yona Mc Dae him (5 C2) "Ste Bech, 8, 85 95. 1 oltht ad Som, Bit em) 3610, "Det B so 08, 18 2. = CVCLoWexXVLAMENYLACETONETRILE 25 «-CYCLOHBXYLPHENYLACETONITRILE (Cycohexanencetonitile, eens!) eaten [ CaHANTINHE—C—SIL NINH cata —e—st-NN TCs As catanNt 1% cana #8 cate 2 5 2a CoHANEENH? Ons + CelfaNHNHCSNHs + CoHNE aed y Jour sat sen Carn 1. Procedure A. PhonUiydresine salt of f-pherslitilcarbasic acid. Tn ‘HL threenecke lsh, ited with w mechanical sizer, a con Genser, and dropping funnel, is placed a soltion of 128m (1.3 moles) of pure resid phenylhydrazine in 600 ml. of ordinary ether. To the vigorously stirred mixture, 82 ml. (086 tle) of carbon disulfide I slded fa the couse of 30 minutes (Note 1). After the mixtre has heen sired for an atonal 30 minutes, the precipitate is fitered with suction, washed with SO mal of ete, and spread on filter paper for 15-20 minates 2 allow evaporation ofthe ether, The ye ofthe sl is 185g (06-98%) 1. Diphensikecorbasie, The above salt is transfered to 11 beaker, and, while i is continuously stined by hand (Note 2), it is heated (Hood) in a water bath maintained at 6-98° (ote 3), After about 10-18 minutes the material softens rrmzone 9 to. taiyike mass, becomes yellow, foams, and evolves hydrogen silde, After about 20-30 minutes ammenia is evolved. When fdstinct odor of ammonia Ist dteced (Note 4), the beaker is ‘emoved fom the bath, place ina pan of cold water fort minute (Note 8), and then surrounded immediately by cracked kee. ‘About 150 ml of absolute alco! s added, che mixture swarmed slightly to loceen the mass, and the taflyike materia is sired “ntl it is eansformed into a granular preiitae. After theraix: ture has stood at room temperature fr 1 bour, the precipitate is collected on a Buchner funnel and washed with 80 ml. of absolute tleahol (Note 6). The yield of crue diphenylthicarbacide is 100-128 g. (0-15% based on phenylhydrazine) (Note 7) , Dithizne. The crude diphenylthiearbazde is ade toa solution of 6g of potassium hydroxide in 600 mi. of methanol Jina FL round-bottomed ask, The lak is immersed ina boiling rater bath, and the mixture Se refused for exactly $ minutes (Note 8). The rd solution is cooled with ice water and filtered by gravity, Toeoold 1 1 sulfuric aid (200-1100 ml) is added to the filtrate, which s stirred vigorously by means ofa mechanical ster, until the coltion is just acid to Cango ted paper (Note 9). ‘The Blucblack precipitate is Sitered. with suction and swaahed with SO ml of cold water (Note 10). ‘Thecrudecarbazone is lsslved in 500 ml. of 57% sodium hydroxide sation, the mix- ture ie filtered with suction, and the tate i cooled in an ice bath and cided immediately with ice-cold 1 sulfuric acd (abet 650 mi requited) unt ijt acl to Congo red paper ‘The precipitate ie ltered with suction and then washed by tetas. fering itto a 21 beaker and sting it thoroughly with 16-18 cold wate, ‘Ihe mixtures itera, and the proces of washing Tnrepeated until there eno trace of sulfate inthe washings (Note 11). ter air has been drswn through the precipitate on the ‘iichner funnel fr 20-30 minutes, the solid dred in an oven at 40", The prodact st this stage weighs 63-85 g. For puriation, ‘portion of $10 g of the catbazone is placed inthe thimble of Soxhlet extractor (Note 12), covered with ether, allowed to stand for bout, and thes extracted for LS hours, The ratera nthe *himbleis transferred immediatly toa beaker, sired with $0” oncante svwmuses of ether, andthe mixtures filtered with suction until mos, but not all, ofthe liquid is emoved. The wet product then dried by Dressing it between filter papers. ‘The yield of pure dithizone (Giphenylhicarbazone) which decompose sharply at a tempers ture between 168% and 169° is 43-548 g. (50-64% based on phenylhydrazine) (Note 13). 2. Notes 1. A precipitate is formed immediatly upon alton ofthe carbon disulfide; the mixture becomes warm, andthe temperature soon approaches the bailing point. The temperature is maine tained just Below the boling pint; cooling with ce water may he necessary to keep it there. As the carbon dislile s aed, the mixture soon becomes pasty, then more Haid, and finally pasty 2. A beavy glass rd, bent or atten atthe Bottom, serves as an eicient steer 3. Care must be taken that the temperature of the bath des no exceed 98°, I the material remains above 98° fora long pecod of time and/or if snot immesintely cooled ater removal fom the water bath, the product decomposes violently after standing fr 10-18 minutes, 4. Ammonia can be detected by means of litmus paper before the odor is noticeable, but the heating shovld be continued unt there is distinct odor of ammonia Chat no longet). The yield ‘depen upon the rapidity with which the heating is stopped after ‘the fist sgn of ammonia is detect . The mass may be olive-gieen or brown while hot, but it becomes light brown on cooing 6, The precipitate is almost pure white. More dipheny! thiocarbazde erystalize from the red leno trate al wash ing, if they are allowed to evaporate slowly. When the mixture isallowed to stand for some time bore its filtered, the amount of precipitate & increased and that of the materi left in the steae is decreased, 1. Diphenylthiocarbaside does not have a sharp melting point. The compound is reported to become green at 130° tnd melt at 150° to a dark green liguid which decomposes on further heating 8. The solution is ete until it is definitely boiling; then it {sallowed to boil for Sminctes only. Ifthe solution i boiled fora Toner time, te ye of producti decreased ‘9, When the end points reached, the mother liquor i 20 longer rebut colores. 10, Care should be exercised in banding this precipitate or suspensions of it If any of fs piled or splashed, should be removed at once, fr i dries tom light, fine powder which is readily scattered; it dyes the skin black and other material pink. 11. Four or ive washings are usually necessary. 12, The Soxhlet extractor used by the suitors had ca- pacity of 8 ml to the top of the siphon tue, ‘The sizeof the thimble was 33 by 80 mm. 18. The pure compound is completely soluble in chloroform. 3. Methods of Preperation ‘This method of preparation isa modication of the method ‘used by Enl Fischer” Sinilar methods have been described by HL Fischer! Wertheim, and Grammitt and Stickle 2 ache, 1,1 (4); 2, 316 82 HL Pace and Ll i Veen Smone Kom, 4 (835) lean se (8, [Rn rm Chon ats a uy 0. i’ Orit and Sle Inn Chm, An aM, 985082 oncante SexTHSES [ETHYL BENZALMALONATE. (Malone acid, ena! diethyl ester) CaH:CHO + CHy(COOCAHa)2 GoHsCHC(COOCLHEs + HO Ste by 6.1L Asset and FW. Sears (Get fy J. Soma and Faw W, Neo 1. Procedure In. 14, round-bottomed flask, which sited with « Clarke ‘Rahrs column’ witha unt for removing water and surmounted boy a roux condenser, ate placed 100g. (0.68 mole) of ethyl mal- conate (Note 1), about 72-76 of commercial benzaldehyde (ote 2), 27 ml. of piperidine (Note 8), acl 200m of benzene. “The misture ig reise? vigorously in an oil bath at 130-140 nti no more water (total, 1213 ml.) i elected; this operation requires 1-18 ours, After themisture has been cooled, 100m fof benzane ie added and the ssltion is washed with two 100-nl portons of water, with two 100, portions of 11 hydrochloric cd, and then with 100 ml. of a saturated soltion of sium bi- carbonate. ‘The aqueous wash slutios are shaken with a single S0-ml. portion of benzene, the benzene extract is added to the ‘orginal organic layer, and the organic solution is dried with 30g. fof anhydrous sodium stiiate, After the benzene has bean 1e- ‘moved under reduced pressure on a steam bath, the residue is ds- filled under reduced pressure fom a 280-ml. modified Claien fiask well wrapped with asbestos, ‘The yield of colores ety benzalmalonate being At 140-142"/4 mam, (Note 4) is 187= 142g. (89-91%) (Note), "rg Sn 2,72 (94) Ta cca psc erm the Pn se Campy, Hohner New one Soap me 9 Fe 7), [PIV BENZALAALOKATE “ 2. Notes 1. Bp. 91-98%/16 mm, ‘The checkers wed rede ethyl salonate 2. Commercial benzaldehyde which contains 2-89% of ben ‘nie ac is eminently atisiactory. "The acid contents deter- Inined (conveniently by titration of «sample in neutral ethanat ‘with standard alka), ands quantity of aldehyde containing 70. (0.46 mole) of benzaldehyde ie used. Te checkers used 76 g of forninerdal benzaldehyde which contained 87 of benzoic ac 1 pure benaaldehyde is employed, then 2 g. of benasie add should be added ‘ehas eon shown # that piperidine salts and not the fee base act asthe catalyst in the Knoevenagel reaction. The checkers ‘tad ony 431% yield with benzaldehyde containing less than 0.29; of benanie add ‘3. ‘The amount of piperidine that employed depends onthe benasie acd content of the aldehyde it shouldbe slightly in ex- ese of that required to neutralize Uhe benzsic acid. About 1.2 mio piperidine per gram of acd is satisfactory. 44 Another bollng point is 179-1817/10 mm. The bailing points reported for ethyl beazalmalonate vary widely. The fenperature observed depends on the degree of superhating and the rapidity of distillation . Methyl benzalmalonate (bp. M5-146%/2 mm. 169- 1717/10 mm.) can be prepared inthe same manner and in the same apparatus ia yells of 90-94%. 1, Methods of Preparation Ethyl benzalmalonet hs ben prepare by the esteretion of Bensalmalonic acd inthe presence of concentrated sulfuric {dy the ction of beneal corde on sodiomalni exter by the condensation of bensaldeyde ant mlone este nthe pres on a Gag, “peep tn hn how 10.088.“ ‘oRoANE SENTHESES ence of hydrogen chloride" acetic ankydtide,* oF alcoholic piperidine or ammonia; and by the action of pheaylmayoesium bromide on hydroxymethylenemalonic ester [BTHYL (-ETHYLPROPENYL)-METHYLCYANOACETATE (eaten ai, yan Sethgh bam, thle) (cataxc=cyerycoocatt, 2, : [CHsCH=C(C2Hs)C(CN)COOCaH:|-Nat CHACHC(CHIC(CH(CN} COCA Stet by Br M. Hascone ad Aeon C. Coe (Gdally Hh Sonancd Samoan 1. Procedure A solution of sodium thosde & prepared from 9.2 (040 mole) of freshly at sodium and 400 al. of absolute alco (Note 1) in a Li three-necked ack Sted with a dropping funnel, = thermometer, mereary-sealed ster, and a condenser protected by adeying tbe (Note 2). To the stirred solution, whichis kept at ~5" (conveniently by partially immersing the ask in & Dry {cebath), 72g (040 mole) of ethyl (1 ethylpropylidene-cyano acetate (p. 46) is added dropwise from the funnel during 8-10, Iinutes, After the mixture has been sire for an slitonal 20, minutes at —S*, 625 g. (04 mol) of methyl iodide is added from the dropping funnel as rapidly as possible, ‘The fask is heated immediately with a strong fame which i withdrawn jut asthe sluton reaches the boiling point. The alkylation is vig- ‘tous, But the fas isnot cooled unless los of material through Ca, Br 1, 18 (16 Ce ed Gry BB 11 (8). ‘nomen Barbi, 3 (0) Cr, Na mai 2, 8 (1850) (eA io erp 91,94 Ur, 8, 0s 98-150). ‘Rapin da Cm Jae, [FTV (LETHYLPROPENYID METHVLCVANOACETATE 45; the refux condenser appears imminent (Note 3). After the spon taneous reaction has subsided, the solution © refuxed until a lec fred Iitmus paper dipped into the liqu and subsequently ristened shows a neutral reaction (15-30 minates). “The elution is cole and ested with 11 of water, nd the ‘ester lyori separated. The aqueous layer is extracted with four ‘530ml. portions of benzene, andthe combined ester and bensene extracts are washed with two 25-ml, portions of water and then fstiled fom a S0O-ml, mifed Clasen flask.” ‘The faction (about 75g) whichis collected at 95-118°/10 mm. is shaken mechanically for 4 hours with 100 mi of 20% sodium bisulfite olution (Note #). ‘The ester layer is separated, the aqueous layer is extracted with three 25: portions of benzene, andthe ‘omnbined exter and benzene extract are washed with 25m. of ‘water. The product remaining alter removal ofthe benzene it isto under rece pressure fom a 250-ml. modified Claien ‘ak or through a Widmer colamn. ‘The yield of ester boiling at 112-118°/8 mm, is 635-68 g (1-89%), 2. Notee 1, Commercial absolute slobol is dried with vodiutn and thy phthalate and relisted. The checkers obtained a con- Sldcraby lower yield in a run employing slohol dried over mag- nesium snethoride 2 The various pieces of apparatus ar dried in an oven and sccembled rapidly in order to exclude moisture ‘3. Excessive eavage(aeaholyis) of Use product is avoided by carping out the allylation rapidly. This procedure mink ries the time during which the product isin contact with sodium sthoride ‘4. This treatment removes ethyl (Lethylproplidene) cyano seetate as 0 water-soluble sodium Disléte addition product (p 4. one Sto Yo 15 198,6 oxcasse suvmases 3, Methods of Preparation ‘The above procedure illustrates a general method fo prepar ing homologous ethyl (ilkylvin!)-alkyleyancacetates by: the allylation of ethyl alkyideneeyanosoetates” ETIIVL (L-ETHYLPROPYLIDERE)-CYANOACETATE (@-Penteoi ai eyanoathsy tyler) (cattg,c0 + cHyemcoocarts HE (catig.C2CteS COO +0 Stil by Ane C. Cor and Eee MHieace, (Chin ye ope nf Su 1. Procedure In a Soom, round-bottomed fiask attached to = modified ‘Dean and Stark constant water separator Note 1) which scon- nected toa reflux condenser are placed 678 (0.60 mole) of ety eyanoacetate (Note 2), $68 g. (0.66 mole) of diethyl ketone (Note 8), 92 g. (012 mele) of emmonium acetate, 30 g. (048 rol) of glacial acetic acd, and 100 ml of benzene. ‘The fas is heated in an oll bath at 100-168", and the water which dist ot of the mixture with the reuxing benzene is removed from the ‘separator at intervals. Refsxng it continued for 24 hours (cev ‘era hous after the separation of water has ceased) (Note 4). “The solution is coled and washed with thee 25. portons of 10% sem ehloede solution, aftr which the benzene is re roves ty disilaton der reduced presure. "The residue is transferred toa Tote, solution of 78g, (0.38 mole) of em ‘mercial sodium bislte in S10 ml. of water fs added, and the ape and Hack J tm Chm Sa, 205 88, ete Min rte ed Hae Jn Chm Se 82 [RMIVL (ETHYLPROPVLIDENE.CvANONCETATE. 47 mixture‘ shaken ona mechanical shaker for 2hours. The turbid solution is lsd with S00 ml of water and extractod with three ‘St-ml. portion of benzene. The extracts are discarded (Note 8) The bist tlution i then cooled in an ice bath, ad an ice-cold solution of 32 g (08 mole) of sodium hydroxide in 130 mi. of vwater is added dropwise with mechanical string. The ester Irhich separates extracted at once wih four 25m portions of benvene (Note 6). ‘The benzene solution is washed with 50 ml ff 1% hydrochloric acid, died for a short time over 20 g. of thy droassosium sulfate tered into #250: died Clsisen flask, anc dstiled under reduced pressure. The yield of ester boing at 123-128°/12 mm. (Note 7) Hx 654-75 g (605-68%) (Notes f, 9, and 10). 2, Notes 1, Another suitable separator is described in Orgomie Sym theses? Any cuntnwows water separator which wil retur the Densene to the reaction mixtre maybe used. ‘2 Commercial ethyl cyanoacetate (Dow Chemical Com pany) was roiled before se; bp. 98-98°/12 mm. "s Diethyl ketone was either putchased from the Bastman Kodak Company and redsilled, or prepared by passing pro- pie acid lowly over a mixture of manganous oxide and d Plate chips in a tube furnace at 420-440°;° the apparatus was Similar to one describe in Orgunic Syathses When prepared by this method the Ketone was distilled, dried over potassium ear- bonate, and redisilled; bp. 100-101", “4 ‘The water lyer (20-25 ml) contang some acetic asd and. scetamile, the acetamide being formed from the ammonium sectate catalyst. 'S Extraction ofthe aqueous solution removes ethyl cyano acetate from the aquooss solution ofthe sedium bislte addition pruuct of ethyl (ethyipopylidene-eyanogcette 6, The unsaturated ester regenerated when the bisuite is nevtraied with sodium hydroxide, The solition i kept cold or Sten. "Sher ad ate Coren 8,8 91) mHOCAHACHO Site by RB. Wooo hehe 5 Hime tnd Rerun J Ames 2. Procedure A solution of 450 (2 moles) of powdered stannous chloride (CoHLOMeCH(COOCAH)s + Ha + C4H:0MgCH{COOCaHa}s ‘cticoct oes on of coocat 0. Sonn ae ons on coon sean? [| \ on ‘ot {Che iy Hh Sonne sad Cone Wace 1. Procedure A. Budo! plonplaclyimalonate, A 1. thee necked, round: bottomed fac i equipped witha dropping funnel (Note ) and a reflurcondenser provided witha eslefum chlorde tube. Before ‘the apparatus is assembled ite washed in the following manner ‘ith absolute alcool which bas been prepared in a distilling ask (Note 2). Ninety aulilters of the ankyrroas ethanol is die tilled through the dropping funnel into the apparats, used for Finsing, and discarded. Inthe reaction fk are placed 125g (0132 atom) of magnesium turnings, 1 mi of carbon tetrachloridem“ ‘onGANIC SvNTHESES (Note 3), and 40 g, (0.25 mole) of malonc ester (Note 3); then 90 ml of absolute aloha is distilled into the droping funnel and transfered tothe das, ‘The rection ie stared by heating and is controlled by applying an ice bath when the condenser begins 10 ood. When the reaction has subsided, 40 (0.25 mole) more of snalonc eter is added at onetime. After tis rection has sub sided, the fas is coled slightly, 180 ml. of dry ether is alded, tnd the reaction mixture is heated on a steam bath for 1 hour, ‘Then 88 g (74m, 057 mole) of phonylacetyl chloride, dite with 90 ml of dry ether, is added slowly Gin about $0 minutes) {rom the dropping fonnel in portions a sch arate thet the vigor fous reaction subsides between additions. When the ation has been completed, the Bask is warm for 10 minutes on » steam Dbath. After the mixture bas been cooled, 100 rl. of water is sudded dropise in about 30 minutes, ‘The oly layer is washed ‘with ewo 100ml, portions of water and died over sodium slate, and the ether Is removed by dislation under reduced pressure (eater pump). The crude phenylacetylmalonic ester (87 ml) which remains is «reddish, somewhat viscous cl B. Buby 1dibydrsy-2-naphthoate. Tha 14. ask volume (a7 ml) of the crude ester Ib added in one lot to 3 volumes (261 mi) of concentrated sulfuric acid without cooing, andthe solution salowed to stand for about I week (Note 4). ‘The whole mixture, including any precipitate which may have formed, is poured slowly with siting into a misture of 1 kg. of ice and 500 ml. of water (Note 8); the slid yellow ester f tered with suction, washed with «small amount of old water, pressed in the Ser for 30 minster with rubber dam, and tnally died in a vacuum desiccator. The ye of ester melting at 80s 85-68 x (60-80%, base on the malone ester se), ‘Recrytallzation of $0 g. of the ester from 309 ml. of 707% leohol (Note 6) yields 45 go yellow, needle crystals melting at’ C. 13:Dikydrozy2-naphthoc ori. Ta a 14. three-necked, round-bottomed fask, ited with a mechanical seer, nitrogen inlet tube, and a condenser carrying a separatory funnel attached bby means of a notched cork, is placed 20.9 g (000 moe) of the NAPETHORESORCINOL 1% recrystallized ester dscl¥ved in 300 ml of dioxane. ‘The appara- ‘ure Burhed with nitrogen, the soltion ie stirred end heaton steam bath, and a slution of 40g, (0.18 mole) of barium hydros- ide octaaydrate in $00 mi. of water is added in the course of 1 hour. Heating snd sting are continued for 3 hours. The pre- cipitated barium salt, which may vary in color from yellow to sreenish gray, is tered from the hot solution and transfered ime ‘mediately 1 a cool (28° solution of 11 ml of concentrated sul frie acid in 185 rl. of water in a S00ca. three-necked, round: bottomed ask ited with # nitrogen inlet tube, a mecanial state, anda condenser The mixture is sired in an atmosphere of nitrogen fr S minutes without heating (Note 7). The precipi tate is removed ly fltsation, washed with a small amount of still water, translereed to a beaker, and extracted with &wo 1G-l, portions of hot absolte alcool. ‘To the warm filtrate fs ‘added 200 of wate, and the solution i allowed to cool in an fe hath for 2 hours. ‘The yield ofthe crude acid which is ob- ttioed by filtration as a fine, yellow powder malting at 135° (ote # i 165 g (0%). D. Nuphioresorcinsl, Ty @ 200ml. thteenecked, round- bottomed fas, supped with nitrogen inlet tbe, aster, and ‘condenser, space 65 mi of water; the waters then boiled to expel discolved oxygen. To the Blling water is added 16 g. of the crude aca (Note 9), and the mixtures bile wit stirring for 2Dhours in an atmosphere of nitrogen. "The water fs decanted from any pasty residue; the ese i oiled with 88 ml of water for 2 hous, and the supernatant liquid is decanted through fter and combined wih Ue frst solution. Just enough sodium hydro tule (about 0.3005 gf aulded to declorze the red solution, 1 gf sou chloride i dislved in te solution, ad the mix. tureisallowed tostand at §*for24hours. The xaphthorececinal precipitates first as an cil, which solidifies to a relish sold on further cooling, and then ts cooriess or slightly yellow plates ‘The yield fs 70-743 g. (S4-S0%), After standing over calium eho in & vacuum desiceator for 1 day, the white or slightly yellow plates melt at 119-122° and the reddish sold mets6 ‘oRaNe SuTHESES “To 100 ml of hot water are added 35, ofthe reds slid, jst enough sodium hydroslte to remove the re eolraton, and 0.3 gf Norte, ‘The miature is filtered, 7 g of sium chloride isclssolved inthe trate, and the solution is allowed to stand ina Closed container at 5° fer 24 hours ‘The yield of naphithoresor Cinol, which separates as large, natty trasparent plates melting at 122-128" (Note 10), is 26g. (75% reoove). 2. Notes 1. In ote to measure the vlume of alcobo to be used, an cual ylume of water (00 ml) i placed in the dropping funnel fd alabels pasted at the evel ofthe water. The funnel i hen femptied and carefully deed 2, A liter of commercial abeolte alcoho ie cried by means of sodium aad ethyl phthalate in 24 dstiling flask equipped with a refx condenser. A short section of rubber tubing sed bby a acrew clamp ie attached to the sidearm ofthe flask. In the next step the condenser isset for downward distillation. 3. The catbon tetrachloride, ether, and maloni ester ace dried over anhydrous magnesium sullate. The malonic ester is Cited before we. 4. The yield of ethyl 13ihydrony-2-naphtboate is de- crosed 1 45% ifthe sulfric acid solution i allowed to stand for only 2 days, 5 Aller about 2 mi of the slfui acid elution has been tude, Ue mixture sized until a yellow sold separates. Pre- Ciptation of the main portion of the produit then cccurs very Ssoothly as the remainder of the sulfuric acid solution is added, ‘6. The ester may be recrystallized also by solution in dioeane and precpitatin by water. 1 An alternative procedure conists in decomposing the ‘uarium salt with hydrochloric ald. However, in the checkers bands this procedae da not yield «barium fre product. 8, The submitters obtained the pure acid as follows: To 0.5 . ofthe crude aid was added 200 ml. of bling wate, and Users or Sans Va. 8 85 098. NAPITHORESORCINOL 7 ture was hested for an instant to effect soition and fitered fmmediatly. The Strate was cooled by vigorous shaking in an ‘bath. Addition oft mi of concentrated hydrochloric arid to the solution caused the separation of crystals, which were col lected after 30 minutes additional cooling ine, washed with ice water, and died in vacuum over phosphorus peataxide. ‘The recovery of material melting in the range of 1385-140. to 165" was 62%, 9. The sold has a tendency to assume a semi-plastic eon sistency, Dut the sze of the mass decreases as decarboxylation 10, If part of the material separates as an oil and solidifies, the appearance of the product may be poor, although the melting pointe 122-124". Seperation as anol may be prevented by slow ‘oolng with slaking and seeing. An alterative procedure for final purification of naphthoresrcinol consist in sublimation at 129-130°/5 X 10-¢ ma, 8, Methods of Preperation [Naphthoresorcinol has been prepared by heating tamino-3 bydrory-4-naphthalneslfoni acd or ie sat ia water or lightly acidic solution * and by eydization of ethyl phenylacetylmalo- pate orof ethyl phenylacetoacetate Phenylactylmalonic eter thas been prepared by condensing phenylacetyl corde and rnaloni ester in ether with sour Pune aR, Ber, 2,140 (99); Ger pa 490 Pr, 420 44 Ge pa 87,08 fry 4 5040410) Cot 2008 5s case. ety tm 28,34 (17); Way Rar ad Hom Che Ania, 3 (i. “min and Wes, J Clem, Sa 14S8 ‘ORGANIC SYNTHESES ‘2.NITRO-4-METHOXYANILINE, (Aolsiine, 2a) NHCOCH, ateoctt 1, Procedure A. 2Nitrostmethorysctoniie, Tn a 21, thneenecked, round/bettomed flask equipped with a mechanical stirrer and a ‘thermometer are placed 123 g. (1 mole) of panisidine (Note 1), 300 ml. of gladal aetic ci and 217 ml. of water. Sting is started, and, when the anisidine has dissolved, 880 g. of ice is tudded.” When the temperature reaches 0-87, 103m. (1 moles) of acetic anbydrdeds added all at once with rp string. Within Several second the contents of the ask set to acrytalline mass nd the temperature rises to 20-25. The fas is heated on & Steam bath until the crystalline material discolves and is then Cooled with tring to 45" at which temperature eystals begin to Separate. An fee bath ie applied, and 100 mi (8% excess) of comeentrated nitric acid (p. gr. 142) is added all at once. The {2NFIRO-EMIETHOXYANILINE, ” temperature tes rapidly to 70° and soon begins to fall. By suitable aljustment of the cooling bath the temperature is main- tained at 60-65" for 10 minutes and then Drought down 10 25° in the course of 10 minvtes (Note 2). ‘The solution is chilled overnight in an ice chest, and the pre- cipitated yellow crystals are collected on a 19-cm. Buchner fu rel, The crystals are washed with 270m. ofie-cold water and presse asdiy ax possible with a rubber dam. The filter cake ean be dred (Note 3) inne or in a vacuum desiccator over ealium chloride snd sida lime. The yield of 2-nito-4-methoxyacetani lide melting at 116-116.° is 188-168 g. (15-19%) 1B. 2Névet-mahoryanifne. A mitre of 160g of nito-t- smethoxyacetanlide and 250 ral. of cold Clasen’s alkali (Note 4) in 21 beaker is stirred and warmal on a steam bath for 15 minutes; i fit becomes Iiguid and then sets toe thick, red paste. After the adaltion of 250 ma. of hot water the mixtare is ‘ered and digested ona steam bath for an aions 18 minutes land then cooled to 0-5°. The product is ellected on a 19-cm. Bichner funne, washed with three 160-rl. portions of fe-cold water and pressed as dry as possible with a rubber dam. The eld of vacuumed product melting at 122.-123° is 122-4 (95-97%). 2, Motes 1. Eastman Kodak Company's Practical grad of panildine swan sc 2 In a run jn which the mixture was allowed to cool spon ‘aneonsly from 65° the product became dark. 'S. Drying is unnecessary if the 2ni0-4methoxyacetanide fs used in tep B. ‘The material may be recrystallized with 979% recovery fom diute aqueous alcoho (2 ml. of 95% aol and ‘Ul of water per gram). ‘The product eo obtained mells at 165-17" “4, Chase's alkalis prepared by dssulvng 88 of potassium Inyo in 6 of water, cooling, and cuting to 280 ml. with ethanol» ‘onoaNte sy TmESES 8, Methods of Preparation 2.Niteo--methoxyacetanilde as been prepared by the ntea- tion of pracetaisdes” The procedure described forthe nitration Isesentally that used by Lothrop. 2.Nitro--methoryaaline bas been prepared by heating nitro lnydroquinone dimethyl ether with aqueous ammoaia;® by beat Ing the ttramethylammonium salt of $itro-t-aminophenol;* by the bydvolysi of 2nitro--methonyacetanilide with elo- holc potassium hydroxide "or hydrochloric acid “and by the Inydrlyss of the ptlucnesulfonamides the Sitrobenzenesal- enamide the Snitro-ptolueneslfonamide? and the acetyl derivative of the p-toluenesillonamside *of2xico-b-methonyani line with concentrated sulfuric ac ITROSOBENZENE catnos Ee cattantiont SE, egtaxo Sei i Cuno H. Cont, Cet M Meio, (hekeliy WE. Hust NC. Do and F Basar 1. Procedure A mista of 250ml. (244 moles) of nitrobenzene (Notas and 2) ava solution of 10 of ammonium chloride in $1 of water in a) Minty, Any 2, 289 (1890 0) even, er, 39,295 (18); Sober 98, 56 m3) 1, 305 Gy Tat td ae al chen pn S89 2 EOI ain, "esi Gor pe ove rd, 1.22 68 ‘tae Jr Ch 6 0 “Revi Bry $1508 (9); Senor, J. Gen. Chom (CS, 1, sss iy 3800 Gt "evra Ler, 35192) "Ravi ad eh, er 1, 3861900, rTmosomrzest a 1 Saal. crock (Note 3) i steed vigorously (Noted), ad 12 g {15 moles) of ine dust (90% zine) is added in small portions lover period ofS minates. About 5 minates after th adition of the sin the main reaction occurs and the temperature rss ‘When the temperature reaches about 65°, enough ie fs added to the tiered mixture to bring the temperature down to S0-85* (Note 5). Twenty minutes iter the adition of zine was started, the solution filtered through a 24-cm. Buchner funnel and the zine one residues are washed with #1. of ailing water. ‘The filtrate and washings are combined ina 6gl. crock (Note 6) and ‘cooled immediately (Note 7) by the addition of enough ice to bring the temperature to 0° to —2° and leave at least 1 kg. of {ce unmeled ‘To thiscald vltion or suspension of phenylhydrosylaming, ‘cold soliton of sulfuric ac (750 ml of concentrated acid and Sulicient ice to bring the temperature down to ~S°) ie added With siting, An ie-cold solution of 170g of sodium dichromate “inydrate in $00-750 ml of water is added! a rapiy a it can be poured into the mixture, whichis ated oF swiled (Note 8) [Aer 2to 3 minaes, the straw colored precipitate of nitreobes: ‘ene is collected on & Buchner funnel and washed with 1 lof water (Note 9). "The crude nitrobenzene is steamed (Note 10) and the tate i collected ina rcriver could by foe (Note 11). The aitriobensene is finely ground in a mortar, transfered to a Dachner fonnel, nd washed with water until the washings are 0 longer brown. After it hasbeen sucked as dey as posible on the filter the nitrsclenaene is pressod between layers of filter paper (or other porous paper). One or two changes of paper may be aeotstty. ‘The yield of nitrovobenzene melting at 61-67" i 128 138 g. (49-537) (Notes 12 and 13). Ifa purer product is de the crade sitrosobensene can be recrystallized from a ‘nal amount of alcohol with good cooling, and the product dred ‘over calcium chloride at atmospheric presi,2. Notes 1. Commercial nitrobenzene of goo quality is satisfactory 2. Contact with nitrobenzene, phenylhydrosylamine, and nitrosobenaene oF prolonged breathing of the vars should be avoided ‘5 The checkers wed & 121, round-bottomed Bask, 4. Vigorous stirring i necessary in order to prevent the sine ‘ast frm enking onthe hettom of the crock. The submitters em: Played two mechanically diven stsers in order to keep the ine dust in suspension. ‘The checkers ased a single paddle Stier sccessaly 'S. At higher temperatures secondary reactions take place, 6. The checkers used a 224 round-bottomed Ass, 7 Since gphenylhydroxylamine decomposes on standing, the filtrate should be cooled as soon asthe ftration is completed, tnd the oxidation to nitrossbenzene should be earted out imme Giaely. An exces of fe should be present since the exida tion reaction & exothermic and the temperature of the soliton should stil be near 0° ater the oxidation. At higher tempera ‘tres oxidation products other than nitrsobenzene are produced 8. Tt is important to add the dichromate solution eapidly in order to obtain a god yield of easly dterable product. Tn a unin which the dcromate solution was alded over a period of 25 minutes, ony a 10% yield of nitrotobenzene was obtsined '9, This proct i stable foraboxt a week if kept at 0 10, Connections should be of glass since cork and rubber are attacked realy. Since nitrobenzene decomposes at the ele- vated temperature, it should be steam-distillel as rapidly” as posible. IF several rane are male, not more than four or five Should be combined for distillation. A’ Hoplcine sill head is ‘Eectve for preventing contamination. ‘The nitrosobenzene condenses toa green Iiquid which sli fies tom white solid, Care should be ten thatthe slid docs not clog the condenser, Disilation is stopped when yellow oily ‘material appears in the condense. NrTROSORENEN ss 11 Cooling ofthe receiver fs necessary because the nitroo- ‘benzene has very high vapor presure at room temperature 12, Velde as high as 65-70% have been obtained. fn smaller 18, Nitzosobenzene can be Kept at room temperature in a closed contalner for 1-2 days. Over longer periods it should be stored at 0" 3, Methods of Preparation ‘Nitrsobensene can be prepared by the oxidation of aniline sith permonotulure acid or peracetic acid and by the oxida tion of &phensiydeonslamine? which i prepared y’the redue- tion of nitrobenzene, ‘cae Zone, Che, 1,58) sDlkecend Ke e184. "Rampoa, Bre, 58 (0), Pansat Maas, 7m Chom Se 86, ms io,sm oncante svwmses PENTEN-LOL, cH—cH cas Le 4+ sock, Ca, ducuon NY 0" cHe—cH Le Leaeyt SO¥ + HCL Cue CucH.ct NZ cH cH Le Lacgs ot 2Na ~+ NaOCHACH{CHACHACHs + NaCl Cue Sucusct 0 [NaOCH:CH,CHLCH—CHls + 10 ~+ HOCH.CH.CH.CH=CH. + NaOH Sate LA soon and HB. Sees ‘hed by Karen Dene and Wav Sa 1. Procedure A. Tetrakydesfujursh chloride, Yo w 21. three-necked fas, fitted with a mechanical stir, a dropping funnel, and a ther: smomete, ace placed 408 g. (4 moles) of freshly distil tetra Inydzofarfury! alcohol (Note 1) and 848g (L4 mele) of pyridine. ‘To the rapidly sized misture which Is cooled in an ie bath, 500 g. (4.2 metes) of fesly distil thinayl chloride (Note 1) Js added from the dropping fannel at the rate of 3-5 drops per second. When one third to one-half of the thonsl chloride has ‘ben added, » pasty crystalline mass begins to separate and the temperature begins to rie capily. ‘The temperature should not be allowed to go above 60". As more thionyl chloride i added ‘the mas redisolves ana dask browa liquid forms. When the addition is complete, the bath & removed and the mistare it Stired for 3-4 hours. ‘The ig oe the slurry, if some erytal- eeevren-vo8 % sation has occurred) is poured into a beaker (Note 2) and ex tracted seven times with 00-ml. portions of ether (Note 3); the tether extracts are decanted and combined. The ethers removed by stilton, and the reside is waned three times with 100-m portions of water, dried over ankydnoss magnesium allte, and ‘ile under duced peasure, The yield of tetrahydrofaeary] lori boiling nt 41-42°/11 mm, (17 48"/15 mm) is 354-360 (3.78%). 1B, ¢Penten-Fol, 24, three-necked Sask containing 112 g (4.87 moles) af posedered sodium (Note 4) under 700 mi of aa- Iaydrous ether # ted with a mechanical ster, e separatory funnel, and a refux condenser with a deying tube. A few mil- liters (2-3) ofa mixture of 300g (2.5 moles) of tetrahydeofururyt chloride and 300 ml. of anhydrous ether is added to the rapidly tired suspension. A vigorous reaction occas, andthe solution tama be, The remsinder ofthe solution of the chloride is then tulded dropwise over a period of § hours, ding which time the flask i cooled in an ice bath (Note 5). When the adition is complete, sting fs continued for 2 ours, ‘The suspension is ‘lccanted from any sodium that remains (Note 6 int dry beaker fd decomposed with scent ice water to give two liquid layers. ‘The ether layer is separated and dried over magnesium sulfate Alter the resnoval ofthe ether by distillation ona steam cone, the residues dstled. ‘The yield of tpenten-t-l boiling at 134-137° 161-178 g. (76-85%). 2. Notes 4. Undisilled commercial thionyl chloride and Eastman ‘Peactial tetrahydrofururylalabol may be used, but the yields ‘ate lightly lower (65-70%). 2, The checkers foun ical to separate the ethereal extract from the residue when the mixture was in a large separatory funnel "3 The yield wil be low if extraction it incomplete, It is ‘advisable to ati with « heavy glas rod and break up any lumps that have formed,% oncaNte svwTmESES 4. The powdered sedium is prepared tnder ot xylene with the aid of 4 Hershbergstrer;* the xylene fs decented and te- placed with ether, 5. The ice bath is not used until the reaction has desaitely started, 6. Occasionally a Hite sodium is left on the bottom of the ‘ask ‘This is destroyed with aleahol and the Mas i washed with 8. Methods of Proparaon “Tetrahydrotufury chloride as been prepazed rom the alco- hol and thionyl chloride? or phosphorus trichloride, 4-Penten- rol bas been prepared from tetrahydofurfury) bromide or chloride and magnesium or sodium. + PPHENYLAZOBENZOIC ACID (Benzo aid, pphenslazo-) CaHlNO + HuNCWHCOOH — CallgN—NCGHACOOH + 140 ‘stmt by Haas D Asn (hed ty WE Baoan N.C. Das 2. Procedure Fifty-four grams (0.9 mole) of raminobentoie acd is i solved in 390 ml of warm gical acti asi ina. Erkenmeyer ask. The actin i cooled to room temperature, 42. (0.9 re) of nitrosobenzene (p. 80) is add, and the mixture Shaken until the nitrobenzene dsslves. The dask is stop- $e Sr 280, {fae mo iy 8, “Pu nm, 6) 34 O90) 78 C9, {Riles Je Sgn {ml i 3: Ch So, 8, 2. pPmENYLARDRENZOYL CHLORIDE 7 ‘ered, and the solution i allowed to stand for 12 hours at roont temperature. The product besos to crystallize after about 15 “The p-phenylazobenzoc acid is collected on a Bichner Funnel (ote and washed with acstc acid and with water. Te yield of al-dred acd melting at 248-247" coe. is 2 g. (105%). BY rerysalizaton fom 95% alcoho (00 ml. per) the acid i ob- thined as orange gold plates which mele a 2485 249.5" cor. the eld is $4. (01%) 2. Notes 1, The solution isnot cooled below room temperature bel ‘tering cooing below 20° brings down impurities. Methods of Preparation ‘The method employed her is esentilly the one described by Angeli and Valor -PPHENYLAZOBENZOYL CHLORIDE (Benzoyl ehiorde,ppeayazo-) HCOsHl + SOC, CuEN-NCH,COCI + HCI + 805 {stil by Grote Conan Gost Nass, Csr CaN 1, Procedure ify gram (0.22 mole) of recrystallized pphenplazobonsole acid (p: 86) (Note 1) and $0, (047 mole) of anhydrous sodium fatbonate (Note 2) ae placed in 11 ask and thoroughly mised by shaking. To this tnature fe added 250 mi. (38 mes) of 981 12 GIN (eA, 7228 9H, "Moen Vas ak iscs onoanic svwrHeses thionyl chloride (Note 3); reflux condenser with drying tube is fitted to the fas, and the mixture erefiwed for 15 hours (Note 4). A condenser is et for ditilation, and as mach as possible of the thionyl chloride is distilled on a steam bath (Note 8) "The acid chloride & dislved by reusing with $00 ml. of, 90-100” lignin, andthe bot solution i decanted from the sodium carbonate onto a uted ter. This proces is repeated with three 130-ml. portions of ligcin. The combined filtrates are concen- trated to $00 ml, filtered ifnecexary, and cooled to 0°. The acd chloride is collected om » Buchner fannel nd pressed as dry ax possible, It is washed twice with 30-0" petroleum ether and Stored in a vacuum desieator over phosphorus pentoxide and parafin shavings (Note 6). The yield of orangeced crystals melting at 95.5-55.5" ls 48g. (89%). 2, Hotes 1. ‘The checkers found that 50g of uarecrytalliced acl gave 45 x of acid chloride melting at 92-04". When tis was rerystal- liad from 90-100" petroleim ether (10 ml. per g), 4.5 fof orange-red crystals melting at 945-95.8° was obtained. “The ‘overall yield of pure acid chloride onthe basis of untecystlizd acids the sume. The use of unecrystallzed ac has an ava ‘age in thatthe volume of solvent required for crystallization of the ac chlovie is much les than forthe ai 2. The use of sodium carbonate s unusual Ts dalmed that the sodium carbonate prevents decompenition and tar formation during the reaction ‘3. The checkers used Eastman Kodak Company's best grade of thionyl chloride 4, Refluing should be earied out under a hood or in an appocats provided wth «gas trap? '5. About 170 ml of goo thionyl chloe can be recovered. 6. The acid chloride holds the petroleum ether tenaciualy [About a week is required for complete removal of the petroleum ether. 0p Soe Cal Yo 1,97 0). REN YLETHLDIMETEYLAMINE » 8. Methods of Preperation ‘pPhenylazobenzoyl chloride (aaoyl chloride) has been pre- pared by the action of thionyl chloride on theacid*4 The method ‘sedis a modiiation ofthat of Ladenburg, Fembols, and Wells? -PHENYLETHYLDIMETHYLAMINE (Phenethyemine, NN-simet-) CatcHLctnNt: +2HCHO + ac00 a catscHscHN Os 2005 + 2140 crt Sc y Ran X Tse a Remar Wino (sto iy eR Sra Jus Sao 1 Procedure ‘To $1.2 g.(t_mle) of 90% formic acid in a $00-ml. round- bottomed Bask (Note 1), cooled in running tap water, ie added slowly 242g, (0.2 mole) of pphenylethylaming’ "To the reslt- ing dear solution are added 48 ml. (0.6 mole) of formaldehyde solution (concentration, 37) (Note 2) and a smal boling-stone. "The Haak is connected to re condenser and is placed in an Nirptenl 389 Nero 8 ‘iran st Peotainsotuy eta kt a8 28 apna ere 4,25 Niro aortaanoooer eNhuiuse a 76 Pree a 32 ce osteo 38 an aoorer 3,97 ‘mes 258 Secon ‘sty ya 98 (peo ter 6 23 Sptomig msc a, bp arn ene 20,70 rpm cheat m6 ty inn ecient ed ee ‘inset can amie 6 ts conn ig ination a une, 1 igi os ‘slawethy group toacartory sreup, oui a8 endeeipat 8 piitcoe Zeman aoe sunyect mxpex: us ono neiperacsir:}, a ea atten 20,95 ‘hemo ld 8,26 Peseta 3 nay unctyeaimte “inch 891 phar na, 5 Pinta 10 886 ‘ imavesomsccr come, 8 07 Fontanini 30 a8 ‘Filan ae Faerie 38 a Pearse 2 acepenthrne 9488 Pcie ay Fenrng eto alan 2,22 Ppa 3 Frere 31 Pp peti 9 1598 5 amp pnehr 2, ‘sper penta 8. ‘whan prude 3 he Php ewe 32.68 ‘eemecnsnd agi Phprswie 9 106; 76 ‘ecard angina 3 Pie ape 8,104 Phe epi 2,70 Boni pct 0a 2 iyaem 4 eyo, 30;8,30 Sauna16 suyucr rex. Poa te 386 iat out as ecu hype 38 27 ens on 3,796 9 ‘ecm mea 4527346 F Papa ‘rose vec 4,8, 11 9% aban cS 0 2[Pwavawac, L--pvmnns) 98, AB ‘Epornon cen Poms 3 femonoon asi ong 2.79 yin 96 502, 89; 37, 88, 94, ose sobs af even) ones, 2,0 | orm. samen 8 05 reco onan. 4cre Pyroiesed 9072 matin 887 ‘one a8 37 sae 10598 10 ete Con aaa. Relay by anagamate sla and Spee ab te tyme end Raney ee Seta ah ‘stesso: ‘os a0 ‘enmane pene, rae ety ony ernie obeyed “nla, ‘ion af @zaptontle to -an8- tata a 8 sys a2 ty ie st eo 2,57 ‘Game 30 57 sunyper mxpex: rd 2S np tM Remind (P-BeS0), 2, 84, 110 epacenat amit goby bree om (as rein 34 22 sinogom throng ae etn 3,1; 38 58 yoaide bomie wom by ho tye atam by mye ee nog aap by 8a up Iya gap by «bromine sam, oor ee rh poor troife nd rin 986 yma a i sam se iy erie 28 plsmet—Cntimad on by cae obo ‘ash a 8, 1, soe yo ‘feaie gosp by hier, 4, Remand pthc 8,8, Sa re, cmt sand pvt ing Seon 4 ponder ck, 4 90 deri campy station ho sey 90 Stowe mt Bae Stephon oda fa aus sour oes Suny a a, cman | Si ing 8.1 aseninn, 90,81 ‘Sonnac ACE, 24 92 Seer 78 Srosen ety Sas She san oe Sin co Speen a Sms yea, SETS [antares ete Seiki isa om, | neato! inh wig t's S| Suan swim 61,565.35 | Suman 86 sa ‘Sitere seco Se ta 825 8 Siow Sn St vat cea Hoon ‘ech gine weno istic ano | ame 8 shee tcse st sees Se Dia au | sme a season a4 23 7 Sim tpn on |S ii Sodium cyanide an, 4428, 18,25) 23, | Sousa, a8 20 sacs ‘Sir acots 2 fein pate 9 | Suuicac i mt Ss Sitters Socata "5,79, 3480. 35 4 sy! lie 15 sylviag a1 | Sierra 7 9 sete pc t78 Sein san a6 Sm bpp Sipura tose | Tac a8. 7 8 Stee || Sune wana 2 BAG sate Dati | ame Sain, Sat pipet .66 | se Santon TN | sagt teeesdaons a Sinsation ts | agen tment ‘Sm adiean2jaq23,s0 | ternmownrane acm a2. 76 SUBJECT INDE 19 naa -Teresnnay psn 2.2 | Ting A105 ‘fermen 3, Sroine ta, (pees asec Sah 69 | p Tito, 16 Timers parowsmiornece | leur Nee 208 one tine te ta engurcie pracemesimre, | tears i, 108 st Siew ‘Toney al 825,88; | poms 100 ‘ty 389 Tepe tering 818,55 2 (Ete ane vratone, 9,569 Bete ein 8,65 ermine | 34S Panini alan 3 2340-Trruaremedesoconan | N-Tier ere, 26 36 6 ‘Tenaaronnmmnacccomny, sx | 24a Temata 3, 0 Tenor ss, 420 18S reine tc ‘romatptemtniuca 98,99 | 3s Tetyphensctne a5 Tetcemaman tie | $4eTemmnensnon 3 Tetog dnb 310 | 13am, 860 ‘Tengnamceanerasnt, #, | 2Af-Tmeroncaseonrn Tecoasnoninae nonin | Plt, A Beaten 8,4 Tain 32,3 ‘Tt LSS 8 en 9 B98 12.68 | Tae ec sah artes et | tummgeanaeteamen ‘Pitunany cay a so | Two tak 2,20, ‘Eee tat at TREE TAG | uum antainse ‘Ticacocm daesanmeney a6 | Unseen boc 444120 ‘sonyncr INDEX rain meray, 38 Wg oe 878 24 868, wien ig, a, 52 Weeace 30 6 ‘eign a 1 yon 86 ‘oor data “Suab Sa ype, | ky 889 tree ln Rowamuedsoacn 8, ‘epilrancin m58 s Natipest 0 stem a0 92 ‘Pisa 358 7 ie tmn 28,2, 82 2850/2871, 88 fea ole mt H ‘eyo 2, 105; 2,98; 94, 18 waders | | eget * BS ga haaORGANIC SYNTHESES ORGANIC SYNTHESES AN ANNUAL PUBLICATION OF SATISFACTORY [METHODS FOR THE PREPARATION ‘OF ORGANIC CHEMICALS CNet Vou 25 JOHN WILEY & SONS, Ixc ‘Lenox: CHAPMAN & HALL, LaurA Ng Rae TABLE OF CONTENTS Sencar ii 2mm Ae Yemen we (Eemararen acacia ot Enmurorscuese) cance Seiciaene Aasmaan Meme Sencar © BeeeeeezerenesmennesseeseuEn