A study of the reactions of with B-Dicarbonyl compounds and their derivatives [and] the synthesis of by the reaction of formyl fluoride with organocadmium bromides by Jack R Gaines A THESIS Submitted to the Graduate Committee in partial fulfillment of the requirements for the degree of Master of Science in Chemistry Montana State University © Copyright by Jack R Gaines (1950) Abstract: The reactions between carbon monoxide and the metal enolates of β -di-carbonyl compounds have been investigated. The catalysts used were tetracarbonyl and dicobalt octacarbonyl. was used, in many cases, in addition to the carbon monoxide. Reactions were also run with the free β -dicarbonyl compounds. No apparent reaction was found to take place between carbon monoxide and these compounds under the conditions which were used. The reaction of O-acetylacetoacetic ester with carbon monoxide and hydrogen in the presence of dicobalt octacarbonyl, however, led to the synthesis of an . The identity of this aldehyde has not yet been determined. Experimental details are given on the preparation of formyl fluoride and the synthesis of 2-methyl-l-butanal by the reaction of formyl fluoride with secondary-butylcadmium bromide. The synthesis of other aldehydes by using formyl fluoride and organocadmium compounds is mentioned. A STbW OP RiSAOTIOKg OIF OARBOR 'M DRGIim R IT g /J-DIOARBQIiIL COSSFOUHDg MB TliElS D:%I7ATI7ES*

T m .G W m g is o r ALDEmmEg m T m E m c T s m o ? mam, mmmm -,smi oRcmocAiamm BRo&EDEg,

Jack E, Caines

. A TRBSIg - ,

- Sabmitted to the Graduate Committee

i n

partial AlfilIment of the reqhiremente

for the degree of

laster of Science, in Chemistry .

at

Montana. State College

Approved;

Boaemanj Montana ,Tular 1950 Q-ILs C f-f3, Zj

— 2 —

TABLIj OF CONTENTS

I . ABSTRACT...... 4

I I . INTRODUCTION ...... 5

I I I . THEORETICAL DISCUSSION ...... 7

IV . EXPERIMENTAL...... 11

M a te r ia ls ...... 11

A p p a ra tu s ...... 11

Dicobalt octacarbonyl ...... 11

Sodium a c e t o a c e t ic e s t e r ...... 12

Sodium a c e ty la c e to n e ...... 13

C opper a c e t o a c e t ic e s t e r ...... 13

Copper acetylacetone ...... 13

Zinc acetylacetone ...... 14

O - A c e ty la c e to a c e tic e s t e r ...... 14

Reaction of acetoacetic ester vdth carbon monoxide and hydrogen ...... 15

Reaction of acetylacetone with carbon monoxide 15

Reaction of acetylacetone with carbon monoxide Jfw and h y d r o g e n ...... 15

Reaction of sodium acetoacetic ester with carbon m onoxide ...... 15

Reaction of sodium acetylacetone with carbon m o n o x i d e ...... 17

Reaction of zinc and copper acetylacetone with carb o n m onoxide and hydrogen ...... 17

Reaction of O-acetylacetoacetic ester with carbon monoxide and hydrogen ...... 17

-T

CM 94725 (Table of Contents) PKt

Preparation of formyl fluoride ...... 19

Seoondary-butylm: £ae slum bromide ...... 20

Secondary-butylcadiidum bromide ...... 20

S y n th e s is o f S - m e th y lb u ta n a l- l ...... 21

Reactions of fori«iyl fluoride witn other organoeadmium bromides ...... 22

V. DISCUSSION OF EXPERIMENTAL RESULTS...... ;

V I. SUKLURY...... 24

V II. ACKNOWLEDGMENT...... 25

V I I I . LITERATURE CITED AND CONSULTED...... 26 - 4 -

I l ABSTRACT

The reactions between carbon monoxide and the metal enolates o f -d i­

carbonyl compounds have been investigated. The catalysts used were and dicobalt octacarbonyl. Hydrogen was used, in many cases, in addition to the carbon monoxide. Reactions were also run with the free

/6 -d icarbonyl compounds.

No apparent reaction was found to take place between carbon monoxide and these compounds under the conditions which were used. The reaction of

O-acetylacetoacetic ester with carbon monoxide and hydrogen in the pre­ sence of dicobalt octacarbonyl, however, led to the synthesis of an alde­ hyde. The identity of this aldehyde has not yet been determined.

Experimental details are given on the preparation of formyl fluoride and the synthesis of 2-methyl-l-butanal by the reaction of formyl fluoride with secondary-butylcadmium bromide. The synthesis of other aldehydes by using formyl fluoride and organocadmium compounds is mentioned. II. IN TH :-DTinTiaN

The use of carbon monoxide as an addition reagent in organic syntheses has become of great technical importance. The number of types of compounds which may be synthesized by the use of carbon monoxide have been greatly increased within the past few years.

The synthesis of methyl alcohol and higher alcohols from carbon mon­ oxide and hydrogen ^ ^ is carried out on a commercial scale. Both lab­ oratory and industrial reactions are knovn for the preparation of aldehydes, aliphatic and substituted aliphatic acids. The commercial production of acetic acid and its higher homologs by E.I. du Pont de Nemours ^ Is accomplished by the following reaction:

BP3 +• H2O CH3OH + CO CH5COOH 75 atms., 125-180*0^

A sim ilar reaction between ethylene and carbon monoxide yields propionic acid C52) . By using various starting materials, hydroxy-acid:: , amino-acids ^ and polycar boxylic-acids ' have been produced by du

Pont. Gattermami and Koch ^ - have shown that aromatic aldehydes can be prepared by the reaction of aromatic hydrocarbons with carbon monoxide and dry hydrogen chloride in the presence of anhydrous aluminum chloride and a small amount of cuprous chloride. Gutiike^,A)' has reported the synthesis of by the reaction of and carbon monoxide in the presence of anhydrous aluminum chloride and titanium tetrachloride at high pressures. Both inorganic ^ v'' and organic bases ^ will react with carbon monoxide, under pressure, to yield formates or other addition compounds. Two such reactions are: - 6 -

KOH ( a q .) + CO ----- I^O 0Ct---- ^ HCOOK (98>) 20 atm .

CH3OH + CO HCOOCH3 200-400 atm ? 7 0-10 0°C .

Aldehydes have been synthesized industrially by reactions between carbon monoxide, hydrogen and olefins in the presence of catalysts and tinder conditions of high pressure ^ (31^ This process is known as the

"oxo" process. Adkins and Krsek (Z) (3) have studied laboratory conditions under which certain unsaturated compounds w ill add carbon monoxide and hydrogen in the presence of dicobalt octacarbonyl. These reactions yield, in nearly all cases, a high percentage of a single addition pro­ duct. An illustrative example is given with allyl acetate:

Ch2=Chch2 OOcch3 + co + h2 gow-loo^^/^s.i^ Ch3 Cooch2 Ch2 Ch2 Cho 110-125°c!

The increasing importance of carbon monoxide as an addition reagent in organic syntheses was one of the reasons for the investigations con­ sidered in this paper. One of the original purposes of this investigation was the synthesis of aldehydes through the reaction of carbon monoxide and hydrogen with -dicarbonyl compounds or their derivatives.

Formyl fluoride (Zl) is the only acid halide derivative of which has been isolated. It has been postulated that the hypo­ thetical formyl chloride is formed as an intermediate in the Gattermann-

Koch synthesis of aromatic aldehydes (H ).

Gilman and Nelson (13J have shown that organocadmium compounds w ill react with acid chlorides to form ketones. Ihus experiments were carried - 7 - out to determine the possibility of preparing aldehydes through the reaction of formyl fluoride with organocadmium compounds.

I I I . THEORETICAL DISCUSSION

No work, up to the present time, has been reported involving reactions of carbon monoxide and /S -dicarbonyl confounds or their metal enolates.

Most of the work dealing with the reaction of an organic salt of any type with carbon monoxide, is that of sodium ethoxide and carbon monoxide.

Stabler (26) ^as reported that alcohol free sodium ethoxide will react with carbon monoxide at high pressures to form the addition product

NaCOOC2H^. Scheibler and Frikell (^ J j however, report the formation of a bevalent carbon derivative C(ONa)OC2H5, using the same conditions.

Adiekes, Simson and Peckelhoff (^ state that both the carbon monoxide and the sodium ethoxide used by Scheibler and Frickell were impure, and that there is no reaction between pure carbon monoxide and pure sodium ethoxide, even after 86 hours. Thus there is no substantial proof that an addition product of any kind is formed when sodium ethoxide is treated with carbon monoxide at high pressures. It has, however, been definitely shown by Burrell (°^ and other investigators (^) that a small amount of sodium or sodium ethoxide w ill catalyze the reaction between ethyl alcohol and carbon monoxide. The reaction results in the forma­ tion of ethyl formate in a nearly quantitative yield. This would indicate that the addition of the carbon monoxide proceeds through an ionic mechanism, quite possibly involving the ethoxide .

The addition of carbon monoxide to a carbanion would require that the carbon atom in the carbon monoxide carry a positive charge.

From the work of Pauling and Sheraan (22)(23) it has been concluded that the - 8 -

carbon monoxide molecule consists of three resonating structures:

/ ~ ------/ :c:o: :c::o: :c:::9:

I i i i n All three structures make about equal contributions to the stability of

the molecule. Thus, it seems logical that the type of structure taking

part in an addition reaction depends upon the charge of the ion to which

the addition is being made and to the stability of the product.

Whitmore ^7) has postulated that olefins exist in an activated state

under certain conditions. Formulas IV and V represent the normal and

activated ethylene molecule respectively:

H H H H h : c :: c : h h : c : c : h

The existance of the activated form V has been fairly well verified by

the work of numerous investigators. As previously mentioned, carbon monoxide and hydrogen have been found to add to unsaturated compounds in

the presence of dicobalt octacarbonyl (3). Allyl acetate, ethyl

crotonate, ethyl acrylate, and allyl alcohol are four compounds which were found to undergo this reaction. A probable polarized or activated

form of each compound is given below.

/ - - / H2C-ChCH2 OOCCH3 CH3CH2 OOCCH-CliCH3

VI VII

- / / - Ch3 CH2UOCCH-CH2 H2C-CHCH2 OH

VIII H

The respective products obtained by Adkins and Krsek were y-acetoxy- - 9 - , ethyl/^-formylbutyrate , f t -c a r bethoxypropicmaldehyde, and

7 -hydroxyDutyraldehyde. If the products are compared with the proposed polarized oiecules, it is seen that the addition of the carbon monoxide taxes place on the carbon atom carrying the partial positive charge.

/ 3-dicarbonyI compounds(^ exibit tautumorism:

ROGHpCRi . RC=CHCF' RG' H=CF'

x XI X II

The monovalent salts ofyS-dicarbonyi compounds ^ possess a resonating s t r u c t u r e :

RCCHrCR' *r RC=CHCR' M+ 4 L 6_ %

X I lI XIV XV

A divalent salt, such as copper acety!a c e to n e \ exists in s chelate r i n g :

x z

CH5C=O' 'OrCCH,

XVI

Structures XIII, XIV, and XV ere true anions, while VI, VII, VIII,

and IX possess only partial positive and negative charges. Although It

appears that the preferential addition of carbon monoxide to unsaturated

compounds is on the carbon atom carrying a partial positive charge, it

is still likely, due to the reasonance structure of carbon monoxide,

that n addition to the anion XIV is possible. The structure of the divalent

salts such as XVI and the structure of the ends X and XII resemble the

ethylenic structure of the unsaturated compounds more sc than the - 10 -

,onovalent salts. The ^saturation in XVI is, to a certain degree, fixed due to the presence of chelation.

0-acetylacetoacetic ester is a true etiylenic compound, its activated form is postulated as:

+ - OhsO-OHOOOO2H5 OOCCH5

XVIII

Tills derivative of acetoaectic ester should form the following addition com­ pound with carbon monoxide and hydrogen:

CHO GH5C:CH2C00C2H5 vOOCCH5

XIX

Gilman and Nelson have shov.n that acid chlorides w ill react with organocadaiun compounds to form good yields of ketones. Two such reactions a r e : C2H5CdC2H5 + CHf COCl CH5COC2H5 (46:.:)

CHsCH2CH2CH2CdBr + CHf COCl ------CH5COC4H9 (74 )

Grignard reagents, on the other hand, form alcohols with acid chloride!'^.

The formation of the ketones with the organocadmium compounds is attributed to the slow rate of reaction of these compounds with the carbonyl group\

It is logical, therefore, to assume that formyl fluoride should react with organocadmium compounds to form aldehydes. The proposed reaction of

secondary-duty!cadmium bromide with formyl fluoride is;

C4HgCdBr + HCOF ------*- C4E9CHO - 11 -

IV . iilXHLRIMXMTAL

M a te r ia ls

The acetoacetic ester and acetylacetone were iilastman' s pure or practi­

cal grade. They were properly dried (when necessary) and distilled before use. The inorganic and other organic reagents were of C.P. grade and were used, in most cases, without further purification. The nickel carbonyl, carbon monoxide, and hydrogen were purchased from the Matheson Co. and were used without further purification.

A p p a ra tu s

Nearly all of the high pressure reactions were carried out in a stainless steel, micro reaction vessel, manufactured by the American In­ strument Co. The bomb had a total volume of 183 ml. hen larger volumes of reactants were used, a 500 ml Parr bomb was employed. Kach bomb was provided with a heating jacket which was mounted in an oscillating mech­ anism. The oscillating mechanism was powered by a 1/6 H.P. geared head motor, which ran the contents of the bomb from end to end at the rate of

36 cycles per minute. The reaction temperature was controlled by means of a Brown m illivoltm eter pyrometer. The themocouple was inserted through the end of the heating jacket into the rear portion of the bomb.

The high pressures, necessary for the reactions, were obtained by means of an Aminco gas booster pump. The booster pump gives a maximum cold pressure o f 6000 p . s . i .

Dicobalt Octacarbonyl Catalyst

The preparation of the active Raney cobalt was carried out according to the procedure given by Pavlic and Adkins for the preparation of — 12 —

Raney nickel. The "Raney Cobalt Aluminum Catalyst Powder" was purchased from the Gilman Paint and Varnish Co. The procedure followed for the pre-

( 2 ) paration of dicobalt octacarbonyl, was that given by Adkins and Krsek ' '.

A bout 6 g of Raney cobalt was placed in 120 ml of ether and pressured with carbon monoxide to 3400 p .s.i. The mixture was heated with shaking f o r 6 hours at 150°C. After the bomb had cooled to room temperature, the pressure was 2600 p .s.i., a drop of 800 p .s.i. The dark reddish brown clear solution was separated from unreacted cobalt by centrifugation and decantation. The carbonyl was always used in solution. It was found that the use of cyclohexane as the solvent, resulted in an increased formation of the cobalt carbonyl.

Sodium Acetoacetic bster

A one-liter three-necked flask was mounted in an ice bath and fitted with a reflux condenser, a separatory funnel, and a mercury-sealed stirrer.

300 ml of absolute ethyl alcohol was poured into the flask and to this was added 23 g ( I mole) of sodium wire. As the rate of the reaction became slower, the ice bath was replaced with a steam bath. After the reaction was complete, the solution was cooled to roan temperature with constant s t i r r i n g . 130 ml (I mole) of ethyl acetoacetate was slowly added through the separatory funnel (about .5 of an hour). The reflux condenser was then replaced by a short s till head, and the alcohol was removed by dis­ tillatio n at 35-40°C., under the partial vacuum provided by an aspirator.

When most of the alcohol had been removed, the pressure was reduced (1-

2 mm) and the remainder of the alcohol was driven off with a steam bath.

The flask was allowed to cool to room temperature under the reduced pres­ - 13 - sure. The yield was 150 g or 96%.

Sodiun Acetylacetone

A 500 ml, three-necked flask was mounted in an ice bath and fitted with a reflux condenser, a glass stopper, and a mercpry-sealed stirrer.

In the flask was placed 150 ml of absolute ethyl alcohol and to this was added 12.5 g (0.5 mole) of sodium wire. As the reaction began to slow down, the ice bath was replaced with a steam bath. After the reaction was complete, the sodium ethoxide solution was cooled to room temperature and

50.0 g (0.5 mole) of acetyacetone was slowly added through a separatory funnel. The precipitated enolate was removed by suction filtration and allowed to air dry for 24 hours. The yield was 58 g or 95^.

Copper Acetoacetic Ester (38)

A solution of 130 g (I mole) of acetoacetic ester, dissolved in

300 ml of ether, was thoroughly shaken with a solution of 99.8 g (0.5 mole) of copper acetate monohydrate dissolved in 800 ml of distilled water. The salt which precipitated out was filtered off. The filtrate was neutralized with dilute sodium hydroxide solution until it was only slightly acid. The additional precipitate which formed was filtered off and added to the first batch. The salt was washed until the filtrate gave no acid reaction.

The yield was HO g or 68$.

Copper Acetylacetone (^)

4 9 .9 g ( 0.25 mole) of copper acetate monohydrate was dissolved in

400 ml of distilled water, heated to about 80°C., and filtered. A solu­ t i o n o f 50.0 g (0 .5 mole) of acety!acetone dissolved in 100 ml of water at

80°C. was added with stirring to the copper acetate solution. The salt which formed, was removed by filtration. The filtrate was treated with — 14 — dilute sodium hydroxide until it was just acid. The additional precipi­ tate which formed was filtered off and added to the first batch. Tne com­ bined salt was washed with water until the filtrate no longer gave an acid reaction and then dried for 12 hours at 80-85°C. The yield was 55 g or

85%.

Zinc Acetvlacetone (^8)

To a mixture of 15.7 g (0.125 mole) of zinc carbonate and 25.0 g

(0 .2 5 mole) of acetylacetone, in a 300 ml erlenmeyer flask, was added

200 ml of distilled water. The mixture was stirred for one hour and was allowed to stand for 12 hours. The salt was removed by filtration and dried at 90°C. The yield was 25 g or 75%.

O-Acetylacetoacetic Aster °)

130 g ( 1 .0 mole) of acetoacetic ester was mixed with 158 g (2 .0 m o les) of and 170 g ( 1 .5 moles) of acetyl chloride was slowly added through a dropping funnel. ( The acetoacetic ester was dried over calcium sulfate and distilled; the pyridine was dried over sodium hydroxide and distilled; the acetyl chloride was freshly distilled before using.) The mixture was vigorously stirred throughout the addition. At the end of the

addition, the solution became nearly solid. The flask was tightly stopper­

ed and allowed to sit for 2 d a y s . 300 ml of ether was added and the

pyridine hydrochloride was filtered off and washed several times with ether.

The filtrate and ether washings were cooled to O0G. and washed with a

cold (0.5 C.) I-N solution of sodium hydroxide until the ether layer

no longer gave an enol test with ferric chloride. The ether solution was

then shaken with cold water, then with cold dilute sulfuric acid, and

finally with cold water. After drying over calcium chloride, the ether - 15 - was removed by distillation and the remaining oil was fractionated under

reduced pressure. The acetylacetoacetic ester distilled over at 100-102°

C. at 9 mm. The average yield obtained was 100-110 g or 58-64/8.

Reaction of Acstoacetic dster with Carbon Monoxide and Hydrogen

1 3 .0 g ( 0 .1 mole) of acetoacetic ester, 50 ml of benzene and 2 g o f

Raney cobalt were placed in the bomb and pressured to 1630 p .s.i. with hydrogen and then to 3730 p .s.i. with carbon monoxide. The mixture was agitated for 4 hours at 150°C. A pressure drop of 310 p .s.i. was ob­ tained. The resulting mixture contained benzene, acetoacetic ester, di­ cobalt octacarbonyl, and some unchanged cobalt.

Reaction of Acetyacetone with Carbon Monoxide

1 0 .0 g ( 0 .1 mole) of acetylacetone, 30 ml of ether and 15 ml of the dicobalt octacarbony 1-ether solution were placed in the bomb and pres­ sured to 3830 p .s.i. with carbon monoxide. The final pressure was 3220 p .s.i., a drop of 610 p .s.i. The mixture was agitated at 100°C. for 3 hours. The resulting mixture contained ether, acetylacetone and cobalt acetylacetone.

Reaction of Acetylacetone with Carbon Monoxide and Hydrogen

2 0 .0 g ( 0 .2 mole) of acetylacetone, 28 ml of ether and 15 ml of the dicobalt octacarbonyl-ether solution were pressured to 1980 p.s.i. with hydrogen and then to 4200 p .s.i. with carbon monoxide. The mixture was agitated for 2 hours at°150 C. 20.0 g of acetylacetone was recovered.

Reaction of Sodium Acetoacetic Aster with Carbon Monoxide

1 5 .2 g ( 0 .1 mole) of the salt, I ml of nickel tetracarbonyl and 40 ml of cyclohexane were placed in the bomb liner. The bomb was pressured to - 16 -

5290 p*s.i. with carbon monoxide. The reaction was run at IBO0C. for two hours. The final pressure was :C?70 p .e.i., a drop of 520 p .s.i. The solid was removed by filtration, washed with ether and allowed to air dry. The solid (4 g) was reddish-brown in color. Vacuum aisti-lation of the filtrate yielded an additional 6 g of the brown solid.

A run using 0.05 mole of salt gave a pressure drop of 450 p .s.i.j 0,15 mole of salt gave 610 p .s.i. drop. Both runs had an Initial pressure of

5280 p .s.i. and were carried out at IbO0C. for two hours.

7.8 g of the brown solid was refluxed for 5 hours with 100 ml of I-N sodium hydroxide solution. The solution was acidified with dilute hydro­ chloric acid and fractionated. The fraction collected under 60°U. was ldenltifled as acetone by the formation of its 2,4-dinltrophenyltp draalne deriv tive (m.p. 125°C. -i^ ).

A suspension of 21,5 g of the brown soliu in 150 ml of anhydrous ether, was placed in a 200 ml three-necked flask. The flask was provided with an inlet tube, a mechanical stirrer and a conaenaer-outiet tube com­ bination. The flask was cooled in an ice bath and dry hydrogen chloride was slowly passed into the stirred suspension for 5 hours. Dr; air as then drawn through the inlet tube for about one hour, Tne mixture was filtered and fractionated under reduced pressure. 6.9 g of a colorless oil was obtained at 72-72°C. (12-15 mm). Beilstein lists the of acetoacetic ester at 12.5 mm as 71°C. 0.78 g (0.006 mole, based on the molecular weight of acetoacetic ester) of tne oil and 0.62 g (0,006 mole) of phenylhydrazine were mixed in a small beaker and allowed to stand over night on a steam plate. The resulting viscous oil was stirred with ether; - 17 - this resulted in the formation of a white crystalline solid. The solid was removed by filtratio n , washed with ether and dried at IOO0C. A f te r

recrystallization from alcohol, it melted at 1270C. Using the same pro­

cedure, ethyl acetoacetate forms 3-methyl-l-phenyl- 5-pyrazolone (17)(27 ) i which has a of 127 C. By using an excess of phenyl- hydrazine, both the oil and acetoacetic ester '-*-7) xl^) yield a h siting, insoluble white solid. The oil was, therefore, acetoacetic ester.

Reaction of Sodium Acetylacetone with Carbon Monoxide

12.2 g ( 0 .1 mole) of the salt, 25 ml of ether and 15 ml of the dicobalt octacarbony 1-ether solution were placed in the bomb and pressured to 3730 p .s.i. with carbon monoxide. Uhe mixture was agitated for 2 hours at 150°

C. A drop of 360 p .s.i. was obtained. The solid was removed by filtra­ tion and washed twice with ether. 7 .2 g of the solid was refluxed with 200 ml of distilled water for one hour. About one ml of acetone was obtained upon distillation. The residue consisted of a resinous material which

could not be identified. 7 .2 g of the original salt gave 2.5 ml of acetone when refulxed for I hour with 100 ml of distilled water, a d ro p o f 350 p . s . i . was obtained when 40 ml of ether was subjected to the same conditions.

Reactions of Zinc and Copper ^cetylacetone with Carbon Monoxide and Hydrogen

Typical runs in the presence of both nickel tetracarbonyl and dicobalt

octacarbonyl resulted in the reduction of the copper compound to m etallic

copper and acetylacetone. The zinc salt, under the same conditions was

recovered unchanged at the end of the reactions.

Reaction of O-Acetylacetoacetic Zster with Carbon Monoxide and Hydrogen

A description of a typical run is given as follows: 34.4 g (0.2 mole) — 18 — of acetylacetoacetic ester, 40 ml of benzene and 2 g of Haney cobalt cata­ lyst were placed in the bomb. The mixture was pressured to 1500 p .s.i. and

3400 p .s.i. with hydrogen and carbon monoxide respectively. The mixture was agitated for 4 hours at 150°C. A pressure drop of 1750 p .s.i. was ob­ tained. Fractionation of the product yielded the following fractions:

1. Benzene.

2 . 16 ml of a clear, low boiling liquid.

3. 17 ml of a colorless oil (50-80°C., 12 mm).

4. 17 ml of a colorless oil (85-100°C., 12 mm).

5. 23 ml of a high boiling residue.

Fraction 2 contained 3.4 g of acetic acid, the remainder being benzene.

Fractions 3 and 4 were redistilled to give 15 g of a colorless oil, X

(b.p. 88-90°C. at 11 mm), 4.1 g of acetic acid, and some higher boiling m a t e r i a l .

Identification of Uil X

The oil was insoluble in water and % NaHCOg solution; soluble in 5/»

NaOH, c o n c e n tra te d HgSO^ and 85$ H^PO/^. W ith th e s u l f u r i c a c id i t gav e a yellow colored solution. A small amount of produced a brownish precipitate.

Its reaction with litmus was acid. It gave a silver mirror with

Tollen1s reagent and an immediate deep purple color with bailiff's reagent.

I t s 2 ,4-dinitropheny!hydrazine derivative melted at 49-50°C. A serai- carbazone derivative could not be obtained.

6 ml of the oil was refluxed for 24 hours with 100 ml of 20$ HNO-^.

The solution was evaporated to dryness on a steam bath, with repeated ad­ ditions of distilled water to remove the last traces of nitric acid. A — 19 — white, crystalline solid was formed, it was identified as succinic acid through its neutralization equivalent (obtained, 59.12; calculated, 59.05) and its p-toluidine derivative (rn.p. obtained, 260°C.; literature value^

2 6 0 ° C .) .

The molecular weight of the oil was determined by the freezing point method, the solvent used was benzene. The value obtained by extrapolation to infinite dilution was 147. Investigation regarding the identity of this compound is being continued.

Preparation of Formyl Fluoride

The apparatus which was used consisted of a 200 ml round bottom flask fitted with an efficient reflux condenser. The top of the condenser was connected to a series of two large U-tubes, 25-30 cm in height. The outlet of the second U-tube was connected to two calcium chloride tubes, the first contained sodium hydroxide pellets and the second contained fused calcium chloride. The apparatus was flushed with hot, dry nitrogen for 2 hours immediately before using. The anhydrous formic acid, used in the pre­ paration, was prepared by refluxing commercial 98- 100,0 formic acid with phthalic anhydride for 2-3 hours and then distilling the mixture.

19 ml (0.5 mole) of anhydrous formic acid, 57 ml (0.5 mole) of ben­ zoyl chloride and 21 g (0.5 mole) of sodium fluoride were placed in the round bottom flask. The flask was then connected to the condenser, the temperature of which was held at 10-15°C. The first U-tube was sur­ rounded by an ice-salt bath and the second U-tube was surrounded by a dry ice-acetone bath (-80°C.). The reaction flask was heated on a steam bath until the reaction began. The reaction proceeded so rapidly at times. -ZO- that it was necessary to remove the steam bath and cool the flask with cold water. As the rate of reaction becan to decrease, the steam bath was replaced and heating was continued for 30 minutes, i'he average yield of formyl fluoride, which collected in the second U-tube, was 7-8 g or

2 9 -3 4 $ .

Secondary-Butvhna^neslum Bromide

The general procedure for the preparation of a Grignard reagent is given by Gilman, Zoellner and Dickey .

In a three-necked flask fitted with a reflux condenser, a mercury- seal stirrer, and a drop funnel were placed 3 g (0.125 mole) of dry mag­ nesium turnings, 25 ml of absolute ether, and a small crystal of iodine.

17 g (0.125 mole) of secondary-butyl bromide was placed in the drop funnel and after 10 drops of this halide had been added to the reaction flask,

75 ml of absolute ether was added to the drop funnel. The reaction was

started by means of gentle heating. Once the reaction had begun, the mo­ tor driven stirrer was started and the secondary-butyl bromide-ether sol­

ution was allowed to flow into the flask at a rate of 1-2 drops per second.

The stirring was continued for an additional 30 minutes after the contents

of the drop funnel had been added to the flask. The ether solution ol the

secondary-butylmagnesium bromide was used imr ediately to prepare the cad­

mium compound.

Secondary-Gu ty lcadmium Bromide (7 ) The procedure suggested by Cason was followed for the preparation

of th is compound.

An additional 50 ml of absolute ether was added to the Grignard re- - 21 - agent prepared by the above procedure. The drop funnel was replaced by a large test tube containing 22.9 g (0.125 mole) of anhydrous cadmium chloride.

The connection between the flask and the test tube was a short piece of

Tygon tubing. The cadmium chloride was added to the secondary-butylmagnes- ium bromide—ether solution during a period of 15—20 minutes. The solution was vigorously stirred throughout the addition and for a period oi 30 m in­ utes following the addition.

Synthesis of 2-I-ieth.yl-l-butanal

The formyl fluoride which was collected in the second U-tube, was distilled into a glass jacketed drop funnel containing 30 ml of absolute

ether. The drop funnel jacket was filled with a dry ice-acetone mixture.

The large test tube connected to the flask containing the organocadmium

compound was replaced by this drop funnel. The organocadmium bromide-

ether solution was cooled with a dry ice—acetone bath and the formyl

fluoride-ether solution was added over a period of one minute. The mix­

ture was stirred during the addition and for three hours thereafter. Tne

mixture was allowed to come to room temperature by standing over n i,n t.

The mixture was hydrolized with 30 ml of dilute sulfuric acid and the

ether layer was separated. The aqueous solution was extracted twice with

50 ml of ether. The ether solutions were combined, dried over calcium

chloride, and fractionated. After the ether had been removed, 3 ml of a

colorless liquid (b.p, 85—90°C., 640 ram) was obtained.

This liquid gave a positive Tollen1s and bchiff1s test. Its 2,4-

dinitrophenylhydrazine derivative melted at 120 C. huntress and - 2 2 -

Kulliken give the boiling point of 2-methyl-l-butanal and the melting point of its 2,4-dinitrophenylhydrazone derivative as 92-93°C. (760 mm) and 120.5°C. respectively. The yield of 2-methyl-l-butanal was 28% of theoretical.

Reaction of Fonityl Fluoride with Other Organocadmium Bromides

By using the same procedure, phenylcadmium bromide gave a 4-6% yield of benzaldehyde. It was identified by its 2,4-dinitrophenyIhydrazone derivative (n.p. obtained, 235°0.; literature value ^ 6 )^ 235-237°C.).

Normal-butylcadmium bromide gave a very small yield of an unidentified aldehyde, probably normal-valeraldehyde. - 23 -

V. DISCUSSION QF E.v '^KlM^NTAL RESULTS

The fact that no definite reaction resulted between the -dicarbonyl

compounds or their metal enolates and carbon monoxide indicates that these

compounds do not possess the necessary structure for such an addition.

Although the -dicarbonyl compounds and their metal enolates are activated

by resonance, it appears that their activated form bears no sim ilarity to the activated form of unsaturated compounds. It would seem logical, there- ^

fore, that if a compound was incapable of forming an activated molecule

containing a positively charged carbon atom, no addition under the con­

ditions used would occur.

The reaction of O-acetylacetoacetic ester with carbon monoxide and

hydrogen in the presence of dicobalt octacarbonyl supports the theory of

addition given above. Compound XIX evidently loses a molecule of acetic

acid and the unsaturated compound formed is further hydrogenated, in the

presence of the dicobalt octacarbonyl to form ethyl /3-iorray I butyrate.

The evidence thus far obtained, indicates thatthe unidentified oil X is

e th y l /3 -foray!butyrate. The formation of succinic acid by the oxidation

of oil X cannot be accounted for.

The synthesis of aldehydes by the reaction of formyl fluoride with

organocadmium compounds has definitely been shown to be possible. Trie

high susceptibility of formyl fluoride to traces of moisture is one of the

factors which causes the low yields which were obtained. The yield of

formyl fluoride reported by Nesmeyanov and Kahn ^21^was W of theoretical.

The increased yield which was obtained is attributed to the use of sodium

fluoride in place of which was used by Nesmeyanov and

K ahn. — 24 —

V I. SUMMARY

1. It has been shown that no definite reaction occurs between /9-dicar- bonyl compounds or their metal enolates and carbon monoxide or carbon monoxide and hydrogen at high pressures and in the presence of either dicobalt octacarbonyl or nickel tetracarbonyl.

2. A reaction has been shown to take place between carbon monoxide, hydro­ gen and O-acetylacetoacetic ester in the presence of dicobalt octacarbonyl.

A moderate yield of an unidentified aldehyde was obtained.

3. The synthesis of 2-methyl-l-butanal by the reaction of forayl fluoride with secondary-butylcadnium bromide is given.

4. The synthesis of other aldehydes through the use of formyl fluoride and organocadmium halides is mentioned. - 25 -

V I I . ACKNOWLEDGMENT

The author wishes to take this opportunity to express his sincere

appreciation and thanks to Dr. Laurence 0. Binder, Jr. for his personal

guidance and inspiration during this research, and to the staff of the

Chemistry Department for their many helpful suggestions. He also wishes to thank the Office of Naval Research of the Department of Navy for the grant which made this investigation possible. - 26 -

V I I I . LITERATim CITED AND CONSULTED

1. Adickes, Sirason and Peckelhoff, Ber., 67. 1436 (1934)

2. Adkins and Krsek, J.Am.Chem.Soc., %0, 383 (1948)

3. Adkins and Krsek, J.Am.Chem.Soc., 3051 (1949)

4. B rit. Patent, C.A. ^6: P16198 (1942)

5. B rit. Patent, C.A. y.: P16991 (1947)

6. B urrell, Chera.Eng.News, 2£, 1939 (1947)

7. Cason, J.Am.Chem.Soc., 68, 2078 (1946)

8. Claisen and Ehrhardt, Ber., 22, 1010 (1889)

9. Claisen and Basse, Ber., 22* 1244 (1900)

10. Fisher and von Philippovich, C.A. 18: P3170 (1924)

11. Gattermann and Koch, B er., jSO, 1622 (1897)

12. Gilman, Zoellner and Dickey, J.Am.Chem.Soc., jjl, 1576 (1929)

13. Gilman and Nelson, Rec.trav.chim ., 22» 518 (1936)

14. Graves, Ind.Eng.Chem., 22, 1381 (1931)

15. H ill and Kelley, "Organic Chemistry", Blakiston Co., Philadelphia (1947)

16. Huntress and M ullikin, "Identification of Pure Organic Compounds", John Wiley and Sons, Inc., New York (1941)

17. Knorr, Ber., 16, 2597 (1883)

18. Knorr, Ber., 1%, 2044 (1884)

19. Kuhn and Albrecht, Ber., 60, 1297 (1927)

20. McElvain and Weber, Organic Syntheses, 22» 35 (1943)

21. Nesmeyanov and Kahn, Ber., 6%, 370 (1934)

22. Pauling and Sherman, J .Chera.Phys., I, 606 (1935)

23. Pauling, "Nature of the Chemical Bond", Cornell University Press, New York (1945) - 27 -

2 4 . Pavlic and Adkins, J .Am.Cham.Soc., 68, 1471 (1946)

25. Scheibler and Frikell, Ber., 6%, 312 (1934)

26. Stabler, Ber., 4%, 580 (1914)

27. Stolz, Ber., 28, 632 (1895)

28. Tanatar and Kxirovskii, C.A. P1253 (1909)

29. U.S. Patent, C.A. 28: P10474 (1934)

30. U.S. Patent, C.A. 28: P1356^ (1934)

31. U.s. Patent, C.A. 28: P6?234 (1934)

32. U.S. Patent, C.A. 22: P9962 (1939)

33. U.S. Patent, C.A. ^6: P19545 (1942)

34. U.s. Patent, C.A. JiO: P7232? (1946)

35. U.S. Patent, C.A. ZtI: P2433a (1947)

36. U.S. Patent, C.A. ^2: P7324e (1948)

37. Whitmore, :|Organic Chemistry", D.Van Nostrand Co., Inc., New York (1937)

38. W islicenua, Ber., ^l, 3153 (1898)

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