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Title:
A PROCESS FOR MAKING 2-NITRO-1-ETHANOL DERIVATIVES
Document Type and Number:
WIPO Patent Application WO/2012/138494
Kind Code:
A1
Abstract:
A process for making a 2-nitro-1-ethanol derivative of formula III: wherein R3 is as described herein is provided. Novel 2-nitro-1-ethanol derivatives provided.

Inventors:
SWEDO, Raymond, J. (924 A North Boxwood Drive, Mount Prospect, IN, 60056, US)
GREEN, David, G. (2421 Grove Lane, Carey, IL, 60013, US)
COBURN, Charles, E. (306 Barn Swallow Lane, Vernon Hills, IL, 60061, US)
Application Number:
US2012/030502
Publication Date:
October 11, 2012
Filing Date:
March 26, 2012
Export Citation:
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Assignee:
ANGUS CHEMICAL COMPANY (1500 East Lake Cook Road, Buffalo Grove, IL, 60089, US)
SWEDO, Raymond, J. (924 A North Boxwood Drive, Mount Prospect, IN, 60056, US)
GREEN, David, G. (2421 Grove Lane, Carey, IL, 60013, US)
COBURN, Charles, E. (306 Barn Swallow Lane, Vernon Hills, IL, 60061, US)
International Classes:
C07C201/12; C07C205/51; C07C253/30; C07C255/10; C07D319/06
Foreign References:
US5498725A
US2297921A
US2368071A
EP0348223A2
Other References:
VITALY M. DANILENKO AND CO: "Synthesis of beta-functionalized alpha,beta-unsaturated oximes via silylation of nitro compounds", SYNTHESIS, no. 5, 10 January 2002 (2002-01-10), pages 635-647, XP002679983,
F. G. BORDWELL ET AL: "The Taft equation as applied to equilibrium acidities of nitroalkanes, G(CH2)nNO2", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 43, no. 16, 1 August 1978 (1978-08-01), pages 3101-3107, XP55031565, ISSN: 0022-3263, DOI: 10.1021/jo00410a002
GÜRNE ET AL: "On the synthesis and degradation of some derivatives of tetrahydro-1,5-oxazine", BULLETIN DE L'ACADEMIE POLONAISE DES SCIENCES, SERIE DES SCIENCES CHIMIQUES,, vol. III-3, 1 January 1955 (1955-01-01), pages 175-178, XP009160787,
D. RANGANATHAN ET AL: "Nitroethylene nitroethylation of amines", TETRAHEDRON LETTERS, vol. 23, no. 27, 1 January 1982 (1982-01-01), pages 2789-2792, XP55031881, ISSN: 0040-4039, DOI: 10.1016/S0040-4039(00)87459-6
H. HOPFF ET AL: "Zur Chemie des Nitro�thylens", HELVETICA CHIMICA ACTA, vol. 43, no. 7, 1 January 1960 (1960-01-01), pages 1898-1910, XP55031879, ISSN: 0018-019X, DOI: 10.1002/hlca.19600430703
R. L. HEATH ET AL: "286. Aliphatic nitro-compounds. Part VII. Preparation of 2-nitroalkylamines", JOURNAL OF THE CHEMICAL SOCIETY (RESUMED), 1 January 1947 (1947-01-01), page 1486, XP55031877, ISSN: 0368-1769, DOI: 10.1039/jr9470001486
WEI JIN ET AL: "A Highly Effective Bis(sulfonamide)-Diamine Ligand: A Unique Chiral Skeleton for the Enantioselective Cu-Catalyzed Henry Reaction", CHEMISTRY - A EUROPEAN JOURNAL, vol. 16, no. 28, 26 July 2010 (2010-07-26) , pages 8259-8261, XP55031815, ISSN: 0947-6539, DOI: 10.1002/chem.201000964
J. B. TINDALL: "Esters of Nitroalcohols", INDUSTRIAL & ENGINEERING CHEMISTRY, vol. 33, no. 1, 1 January 1941 (1941-01-01), pages 65-66, XP55031811, ISSN: 0019-7866, DOI: 10.1021/ie50373a012
NORMAN LEVY ET AL: "241. Addition of dinitrogen tetroxide to olefins. Part II. Ethylene", JOURNAL OF THE CHEMICAL SOCIETY (RESUMED), 1 January 1946 (1946-01-01), pages 1096-1100, XP55031895, ISSN: 0368-1769, DOI: 10.1039/jr9460001096
G. BARTOLI ET AL: "Highly Efficient Solvent-Free Condensation of Carboxylic Acids with Alcohols Catalysed by Zinc Perchlorate Hexahydrate, Zn(ClO4)2?6?H2O", ADVANCED SYNTHESIS & CATALYSIS, vol. 347, no. 1, 1 January 2005 (2005-01-01), pages 33-38, XP55031893, ISSN: 1615-4150, DOI: 10.1002/adsc.200404171
VANELLE P ET AL: "Preparation and antiparasitic activity of new imidazoles bearing dioxane or hexahydropyrimidine moiety", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 26, no. 7, 1 October 1991 (1991-10-01), pages 709-714, XP023870477, ISSN: 0223-5234, DOI: 10.1016/0223-5234(91)90120-C [retrieved on 1991-10-01]
EDGAR SCHIPPER ET AL: THE JOURNAL OF ORGANIC CHEMISTRY, vol. 26, no. 10, 1 October 1961 (1961-10-01), pages 4145-4148, XP55031925, ISSN: 0022-3263, DOI: 10.1021/jo01068a626
MALINOWSKI S ET AL: "Reakcje nitroparafinow. IV 1,2,3) Reakcje nitrometanu z formaldehydem i aminami", ROCZNIKI CHEMII ANNALES SOCIETATIS CHIMICAE POLONORUM, WARSZAWA : NAKLADEM POLSKIEGO TOWARZYSTWA CHEMICZNEGO, PL, vol. 25, 1 January 1951 (1951-01-01), pages 183-212, XP009160884, ISSN: 0035-7677
PIOTROWSKA H ET AL: "Michael addition of a 5-nitro-1,3-dioxane = Addycja michaela 5-nitro-1,3-dioksanu", ROCZNIKI CHEMII ANNALES SOCIETATIS CHIMICAE POLONORUM, WARSZAWA : NAKLADEM POLSKIEGO TOWARZYSTWA CHEMICZNEGO, PL, vol. 47, 1 January 1973 (1973-01-01), pages 409-412, XP009160885, ISSN: 0035-7677
NOLAND: 'Organic Syntheses, Collective', vol. 5, 1973, JOHN WILEY AND SONS page 833
J.B. MORIN; J.K. SELLO ORGANIC LETTERS vol. 12, no. 15, 2010, page 3522
Attorney, Agent or Firm:
SHALTOUT, Raef, M. (The Dow Chemical Company, P.O. Box 1967 Intellectual Propert, Midland MI, 48641-1967, US)
Download PDF:
Claims:
WHAT IS CLAIMED IS:

1. A process for making a 2-nitroethanol derivative, the process comprising:

(a) providing a compound of formula I:

(I)

wherein R is H or CH2OH, and Riand R2 are independently H, C -C alkyl, halo substituted C -C alkyl, aryl, or furanyl;

(b) converting the compound of formula I to a compound of formula II:

(Π)

wherein R3 is the residue of an alpha carbon reactant or R is -CH2-R4 wherein R4 is the residue of an alcohol group reactant;

(c) converting the compound of formula II to a 2-nitroethanol derivative of formula III:

—^

02N

(III)

2. The process of claim 1 wherein R is CH2OH and the compound of formula I is prepared by reacting tris(hydroxymethyl)nitromethane with a blocking group precursor.

3. The process of claim 1 wherein R is H and the compound of formula I is prepared by reacting tris(hydroxymethyl)nitromethane with a blocking group precursor followed by treatment with base to remove a -CH2OH group.

4. The process of any one of claims 2-3 wherein the blocking group precursor is a geminal diether compound, an aldehyde compound, or a ketone compound.

5. A compound of formula III- 1 :

(III-l)

wherein R5 is C -C alkyl, C3-C8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of C C6 alkyl, nitro, halo, alkoxy, or carbonyl.

6 A compound of formula III-2:

(III-2)

wherein R6 and R7 are independently H, C C6 alkyl, C3-C8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of C C6 alkyl, nitro, halo, alkoxy, or carbonyl.

7. A compound of formula III-3:

(III-3)

wherein Rg is C C6 alkyl, C3-C8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of CrC6 alkyl, nitro, halo, alkoxy, or carbonyl.

A compound of formula III-4:

(III-4)

wherein R9, R10, Rn, and R12 are independently CN, C02H, CO2R13, COR^, H, Cr C alkyl, C3-C8 cycloalkyl, aryl, or aralkyl-, with the proviso that at least one of R9, R10, Rn, and R12 is CN, C02H, CO2R13, or COR13; and wherein R13 is Ci-C6 alkyl, C3-C8 cycloalkyl, aryl, or aralkyl-, and wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of C -C alkyl, nitro, halo, alkoxy, or carbonyl.

Description:
A PROCESS FOR MAKING 2-NITRO- 1 -ETHANOL DERIVATIVES

Cross-Reference to Related Applications

This application claims priority from provisional application serial number

61/472,747, filed April 7, 2011, which is incorporated herein by reference in its entirety. Background

This invention relates generally to a process for making 2-nitro-l-ethanol derivatives. The invention also relates to novel compounds.

The compound 2-nitro-l-ethanol (2-NE) is an attractive synthesis intermediate because of its multiple functionality. For instance, reaction of the -OH group can yield esters, while the carbon alpha to the nitro group can participate in Michael reactions,

Mannich reactions, and the like. In addition, the nitro group can be reduced to an amine.

In spite of its potential utility, 2-NE is not widely used because of problems associated with its synthesis. For instance, in Noland, Organic Syntheses, Collective Volume 5, John Wiley and Sons, New York, 1973, p. 833, a synthesis of 2-NE on a lab scale is described that uses an approximately 10 fold molar excess of nitromethane.

Nitromethane is a detonable liquid and its handling therefore presents challenges, particular when used in large excesses.

In addition to the concerns associated with nitromethane, the 2-NE itself may begin to decompose during distillation, thus further hampering the synthesis. As a result of these problems, 2-NE is not easily prepared and therefore not readily available.

The problem addressed by this invention is the provision of 2-NE derivatives in a manner that avoids one or more of the problems and hazards associated with the prior art.

Statement of Invention

We have now found that 2-NE derivatives may be readily prepared through a process that does not require the synthesis and isolation of the 2-NE compound as a precursor. Advantageously, therefore, the hazards associated with conventional processes may be mitigated or avoided.

In one aspect, there is provided a process for making 2-nitroethanol derivatives. The process comprises:

(a) providing a compound of formula I:

(I)

wherein R is H or CH 2 OH, and Riand R 2 are independently H, C -C alkyl, halo substituted CrC 6 alkyl, aryl, or furanyl;

(b) converting the compound of formula I to a compound of formula II: (Π)

wherein R 3 is the residue of an alpha carbon reactant or R 3 is -CH 2 -R4 wherein R 4 is the residue of an alcohol group reactant;

(c) converting the compound of formula II to a 2-nitroethanol derivative of formula

III:

—^

0 2 N

m .

In another aspect, the invention provides compounds of the formula III- 1 :

(III-l)

wherein R5 is CrC 6 alkyl, C 3 -C8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of CrC 6 alkyl, nitro, halo, alkoxy, or carbonyl.

In a further aspect, the invention provides compounds of the formula III-2:

(III-2)

wherein R 6 and R 7 are independently H, CrC 6 alkyl, C 3 -C8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of C -C alkyl, nitro, halo, alkoxy, or carbonyl. In still another aspect, the invention provides compounds of the formula III-3:

(III-3)

wherein Rg is CrC 6 alkyl, C3-C8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of CrC 6 alkyl, nitro, halo, alkoxy, or carbonyl.

In yet another aspect, the invention provides compounds of the formula III-4:

(III-4)

wherein R 9 , R 10 , Rn, and R 12 are independently CN, C0 2 H, C0 2 R 13 , COR 13 , H, C - C alkyl, C 3 -Cg cycloalkyl, aryl, or aralkyl-, with the proviso that at least one of R 9 , R 10 , Rn, and R 12 is CN, C0 2 H, C0 2 R 13 , or COR 13 ; and wherein R 13 is Ci-C 6 alkyl, C 3 -C 8 cycloalkyl, aryl, or aralkyl-, and wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of CrC 6 alkyl, nitro, halo, alkoxy, or carbonyl.

Detailed Description

Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, ratios, percentages, parts, and the like are by weight.

"Alkyl" as used in this specification encompasses straight and branched chain aliphatic groups having the indicated number of carbon atoms. If no number is indicated, then 1- 10, alternatively 1-6, alkyl carbons are contemplated. Preferred alkyl groups include, without limitation, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl.

The term "cycloalkyl" refers to saturated and partially unsaturated cyclic

hydrocarbon groups having the indicated number of ring carbon atoms. Fully saturated groups are preferred. Preferred cycloalkyl include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. "Cyclic diether" refers to a cycloalkyl in which two of the ring carbon atoms are replaced with oxygen atoms.

An "aryl" group is a C6-C12 aromatic moiety comprising one to three aromatic rings. Preferably, the aryl group is a C6-C10 aryl group. Preferred aryl include, without limitation, phenyl, naphthyl, anthracenyl, and fluorenyl. More preferred are phenyl and naphthyl.

The term "aralkyl-" refers to aryl-C C6 alkyl-. A preferred aralkyl group is benzyl.

"Halo" refers to chloride, bromide, fluoride, or iodide. Chloride and bromide are preferred. Chloride is more preferred.

The term "blocking group precursor" refers to a reagent that reacts with

tris(hydroxymethyl)nitromethane to form the compound of formula I. Examples of suitable blocking group precursors include, for instance: geminal diethers such as 2,2- dialkoxypropanes and 2,2-dimethoxypropane; aldehydes such as formaldehyde,

propionaldehyde, butyraldehyde, benzaldehyde, furfural, chloroacetaldehyde; and ketones such as 2-propanone or butanones (e.g., 2 or 3 butanone), cyclopentanone, cyclohexanone, acetophenone, propiophenone, and benzophenone. Preferred are geminal diethers and ketones.

The formula I compound contains an acidic hydrogen at the carbon alpha to the nitro group or it contains a hydroxy-methyl group. Advantageously, the other otherwise reactive sites of the 2-nitroethanol molecule are blocked in the compound of formula I from further reaction by blocking groups. Consequently, the compound may undergo targeted reactions at the open sites without interference by the other now blocked functionalities.

Compounds of formula I in which R is CH 2 OH may be prepared by reacting tris(hydroxymethyl)nitromethane with a blocking group precursor. The reaction can be readily carried out by those skilled in the art. Examples of suitable procedures are described in US patents 2,297,921 and 2,368,071, each of which is incorporated by reference herein in its entirety. Typically, the reaction between the blocking group precursor, such as aldehyde or ketone, and the tris(hydroxymethyl)nitromethane may be carried out in the presence of a catalytic amount of an acid, such as concentrated hydrochloric acid, sulfuric acid, or methanesulfonic acid. In some embodiments, it may be preferable to use an excess of the blocking group precursor. It may also be desirable to conduct the reaction in the presence of a liquid that is capable of azeotropic removal of the produced water, such as pentane. Once the desired level of reaction has occurred, the product may be purified by techniques well known to those skilled in the art including, for instance, through neutralization of the acid catalyst followed by washing, drying, and distillation. Compounds of formula I in which R is H may be readily prepared simply by base catalyzed cleavage of the CH 2 OH (R group) of the product from the foregoing reaction.

The tris(hydroxymethyl)nitromethane used in the above reaction is commercially available or it may be readily prepared, for instance through the reaction of nitromethane and formaldehyde. In some embodiments, in may be desirable to prepare the formula I compound through a one pot synthesis starting from nitromethane. According to this embodiment, the nitromethane is first reacted with the formaldehyde, followed by reaction with the blocking group precursor to yield the formula I compound. As a one pot synthesis, isolation and/or purification of intermediate compounds is advantageously not required.

When the formula I compound contains a hydrogen at the alpha carbon (i.e., R is H), the compound may undergo carbon-carbon bond forming reactions at this site to yield useful compounds or their precursors. The group added to the alpha-carbon is referred to herein as the "residue of an alpha carbon reactant." Examples of reactions providing such residue include, for instance, Michael reaction, Henry reaction, and Mannich reaction.

The Michael reaction is a well known and highly useful method for the formation of

C-C bonds. In the invention, the formula I compound (wherein R is H) functions as a Michael donor. A wide variety of compounds may function as the Michael acceptor including, but not limited to, acrylonitrile, acrylic acid, methacrylic acid, acrylic acid esters, methacrylic acid esters, acrylamides, methacrylamides, α,β-unsaturated aldehydes, ketones, and esters. The product of the Michael reaction is a compound of formula II in which R is the residue of the Michael acceptor.

The Mannich reaction is also a well known and highly useful bond forming method that involves use of an amine and an aldehyde as co-reactants. In the invention, the formula I compound (wherein R is H) functions as the nucleophile in the reaction. A wide variety of reagents may function as the amine and the aldehyde including, for instance, ammonia, methylamine, dimethylamine, the propylamines and diamines, the butylamines and diamines, the pentylamines and diamines, the hexylamines and diamines; mixed

alkylamines such as methylethylamine; cyclic amines such as cyclopentylamine and cyclohexylamine; heterocyclic amines such as piperadine and piperazine; aromatic amines such as aniline and substituted anilines; formaldehyde, dimethoxypropane,

paraformaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, benzaldehyde. The product of the Mannich reaction is a compound of formula II in which R is the residue of the amine and aldehyde co-reactants.

When the formula I compound contains a CH 2 OH at the R position, the OH may react with a variety of reagents. The product of the reaction between the hydroxy and the reagent is referred to in this specification as the "residue of an alcohol group reactant." Examples of suitable OH reactions include ester formation and Mannich reactions.

Once the desired compound of formula II is formed, the blocking group is removed from the molecule, thus yielding the formula III compound. The blocking group may be removed using methods familiar to those skilled in the art, such as described by J.B. Morin and J.K. Sello, Organic Letters, 12 (15), 3522 (2010), or in EP 0348223 A2. Typically, the removal may be carried out, for instance, by acid catalyzed cleavage of the CRiR 2 moiety followed by base catalyzed cleavage of the CH 2 OH residues.

In some embodiments, compou III are of the formula III-I:

(III-l)

wherein R 5 is C C 6 alkyl, C 3 -C 8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of C C 6 alkyl, nitro, halo, alkoxy, or carbonyl.

Preferred compounds of formula III-l include compounds wherein R5 is H. Also preferred are compounds wherein R5 is C C 3 alkyl, more preferably methyl.

In some embodiments, compounds of formula III are of the formula III-2:

(III-2)

wherein R 6 and R 7 are independently H, Ci-C 6 alkyl, C 3 -C 8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of Ci-C 6 alkyl, nitro, halo, alkoxy, or carbonyl. Preferred compounds of formula III-2 include compounds wherein R 6 and R 7 are independently H or C C 6 alkyl. Also preferred are compounds wherein one of R 6 and R 7 is H and the other is Ci-C 6 alkyl. Further preferred are compounds wherein R 6 and R 7 are both independently selected Ci-C 6 alkyl groups.

In some embodiments, compounds of the formula III are of the formula III-3: wherein R 8 is Ci-C 6 alkyl, C3-C8 cycloalkyl, aryl, or aralkyl-, wherein cycloalkyl and are optionally substituted with 1 or 2 of CrC 6 alkyl, nitro, halo, alkoxy, or carbonyl.

Preferred compounds of formula III-3 include those wherein Rg is C1-C6 alkyl.

some embodiments, compounds of the formula III are of the formula III-4:

(III-4)

wherein R9, Rio, Rn, and R 12 are independently CN, C0 2 H, CO 2 R 13 , COR 13 , H, CrC 6 alkyl, C 3 -Cg cycloalkyl, aryl, or aralkyl-, with the proviso that at least one of R 9 , R 10 , Rn, and R 12 is CN, C0 2 H, C0 2 Ri 3 , or COR 13 ; and wherein R 13 is Ci-C 6 alkyl, C 3 -C 8 cycloalkyl, aryl, or aralkyl-, and wherein cycloalkyl and aryl are optionally substituted with 1 or 2 of

CrC 6 alkyl, nitro, halo, alkoxy, or carbonyl. Preferred are compounds wherein Rn and R 12 are H and R9 and Rio are independently H or CN, C0 2 H, C0 2 Ri 3 , or CORi 3 . Also preferred are compounds wherein Rn, Ri 2 , and R 9 are H and R 10 is CN, C0 2 H, C0 2 Ri 3 , or CORi 3 .

The compounds of formula III, III- 1 , III-2, III-3, and III-4 find utility in a variety of applications. For instance, such compounds may be used as intermediates in the synthesis of commercial chemicals or pharmaceutical agents.

Some embodiments of the invention will now be described in detail in the following Examples.

EXAMPLES

Example 1

5-Nitro-2,2-dimethyl-5-hydroxymethyl-l,3-dioxane is made from 0.33 moles of tris- (hydroxymethyl)-nitromethane (TN, TRIS-NITRO ® , ANGUS Chemical Company) and 3.4 moles of acetone in refluxing pentane containing 0.1 mL of methanesulfonic acid. Water was removed as the pentane azeotrope. When the theoretical amount of water has been removed, the pentane and excess acetone are removed by rotary evaporation at a bath temperature of <35°C at reduced pressure. The resulting crude product is taken up in 750 mL of ethyl acetate. The resulting solution is washed twice with 125 mL portions of saturated aqueous sodium bicarbonate solution, and then it is dried over anhydrous magnesium sulfate. The drying agent is removed by filtration, and the solvent removed by rotary evaporation to give 31.5 grams (50% yield) of the blocked TN.

Example 2

5-Nitw-2,2-dimethyl-l,3-dioxane is made by mixing 5-nitro-2,2-dimethyl-5- hydroxymethyl-l,3-dioxane (0.03 moles) with about 70 mL of 10 wt. % sodium hydroxide solution, and the solution is stirred at 60°C for about 60 minutes. The solution is cooled to about 5°C, and is acidified to pH 5 with concentrated acetic acid. The precipitated solid is filtered off and dried to give a 92% yield of product. Example 3

3-(2,2-Dimethyl-5-nitro-l,3-dioxan-5-yl)propanenitrile is made by slowly adding 1 mole of 2,3,4,6,7,8,9, 10-octahydropyrimidol[l,2-fl] (DBU) to a solution of 1 mole of 5- nitro-2,2-dimethyl-l,3-dioxane and 1 mole of acrylonitrile in 2 L of acetonitrile. The temperature of the reaction mixture is kept at <20°C during the addition. The solution is then stirred at room temperature for about 7 hours. The solvent is removed by rotary evaporation to give a crude product which is taken up in ethyl acetate. The ethyl acetate solution is washed with 6N hydrochloric acid solution to remove the DBU. The solution is then washed with saturated aqueous sodium bicarbonate solution, and is dried over anhydrous magnesium sulfate. The solvent is removed by rotary evaporation to give the product in about 75% yield.

Example 4

5-Hydroxy-4-(hydroxymethyl)-4-nitropentanenitrile is made by heating a solution of 3-(2,2-Dimethyl-5-nitro-l,3-dioxan-5-yl)propanenitrile and 75 mL of concentrated hydrochloric acid in 2.5 L of methanol at 35 -40°C for about 1 hour. The bulk of the methanol is removed by rotary evaporation at a bath temperature of <40°C. The resulting residue is mixed with about 500 mL of water, and the pH is adjusted to about 6 - 7 by adding dilute aqueous sodium hydroxide solution. The solution is then extracted with several portions of ethyl ether. The ether solution is washed with saturated aqueous sodium chloride, and is then dried over anhydrous magnesium sulfate. The solvent is removed by rotary evaporation to give the product in about 90% yield. Example 5

4-Nitrobutanenitrile is made by heating a solution of 1 mole of 5-hydroxy-4- (hydroxymethyl)-4-nitropentanenitrile in 2 L of 10% aqueous sodium hydroxide solution at 60°C for about 1 hour. The solution is then cooled to about 5°C, and then it is acidified to pH 5 by the addition of glacial acetic acid. The resulting mixture is extracted with several portions of ethyl ether. The ether solution is washed with water and is dried over anhydrous magnesium sulfate. The solvent is removed by rotary evaporation to give the product in about 90% yield.